Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal.
Withdrawal (detoxification) is necessary prior to drug-free treatment. It may also represent the end point of long-term opioid replacement treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system. To assess the effectiveness of interventions involving the administration of opioid antagonists to induce opioid withdrawal with concomitant heavy sedation or anaesthesia. Multiple electronic databases (including MEDLINE, EMBASE, PsycLIT, Australian Medical Index, Cochrane Controlled Trials Register, and CINAHL) were systematically searched. Reference lists of retrieved studies, reviews and conference abstracts were handsearched. Randomised or quasi-randomised controlled trials that compared the administration of opioid antagonists under heavy sedation or anaesthesia with another form of treatment. One reviewer assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all three reviewers. As yet, no studies have been published comparing treatment regimes involving the administration of opioid antagonists under heavy sedation or anaesthesia with other approaches to detoxification. Treatment regimes for the studies considered for this review varied in the opioid antagonist used, the dose and mode of administration, the anaesthetic agent, duration of anaesthesia and adjunct medications employed. More detailed monitoring of withdrawal is required before any conclusions can be drawn as to what comprises a typical pattern of withdrawal and what factors might influence the pattern. There is only very limited information on referral to ongoing treatment, and relapse to opioid use. Together with the lack of adequate comparisons, this makes it impossible to draw any conclusions about the long-term effectiveness, or the cost-effectiveness, of withdrawal induced by opioid antagonists under heavy sedation or anaesthesia. Considerably more research evidence will be needed before any conclusions can be drawn regarding the effectiveness of managing withdrawal by administration of opioid antagonists under heavy sedation or anaesthesia. The risk of vomiting during sedation, respiratory depression and cardiac irregularities point to the approach being limited to facilities equipped for intubation, assisted ventilation and a high level of monitoring, and with the capacity to respond to adverse events that might occur. The approach must be regarded as experimental with both risks and benefits remaining uncertain.


t(1;4) translocation in a child with acute lymphoblastic leukemia: a case report.
Acute lymphoblastic leukemia is the most common childhood cancer, with an 80% frequency in children between 1 and 10 years old. The outcome and prognosis of acute lymphoblastic leukemia in children depends on various factors, such as age, clinical and biological features, and cytogenetic factors. We report the case of a pediatric patient, a 4-year-old Moroccan female who was referred to the Hematology and Oncology Department of 20 August 1953 Hospital in Casablanca and diagnosed with B-cell acute lymphoblastic leukemia associated with a rare genetic chromosomal abnormality. Translocation (1;4)(p21;p15) is a relatively rare chromosomal abnormality found in human leukemia and was never described isolated in pediatric B-cell acute lymphoblastic leukemia patients. It showed a good evolution by complete remission and recovery of this patient after receiving all chemotherapy and after 8 years of follow-up.


[Adjuvant therapy of breast cancer with trastuzumab].
With the approval of trastuzumab (Herceptin) in 1998, a new era of breast cancer treatment has been heralded. This antibody is directed at the intracellular domain of a member of the epidermal growth factor receptor family, the so-called HER2 receptor. About 25-30% of all breast cancers overexpress this factor, which is associated with a more unfavorable prognosis. Trastuzumab is indicated for patients whose tumor overexpresses HER2. All previous studies on the adjuvant therapy with trastuzumab show very consistent results and provide evidence that the risk of recurrence can be reduced by half by the antibody. Nevertheless, there are still numerous open and controversially discussed questions concerning the use of trastuzumab in adjuvant therapy.


Understanding smell--the olfactory stimulus problem.
The main problem with sensory processing is the difficulty in relating sensory input to physiological responses and perception. This is especially problematic at higher levels of processing, where complex cues elicit highly specific responses. In olfaction, this relationship is particularly obfuscated by the difficulty of characterizing stimulus statistics and perception. The core questions in olfaction are hence the so-called stimulus problem, which refers to the understanding of the stimulus, and the structure-activity and structure-odor relationships, which refer to the molecular basis of smell. It is widely accepted that the recognition of odorants by receptors is governed by the detection of physico-chemical properties and that the physical space is highly complex. Not surprisingly, ideas differ about how odor stimuli should be classified and about the very nature of information that the brain extracts from odors. Even though there are many measures for smell, there is none that accurately describes all aspects of it. Here, we summarize recent developments in the understanding of olfaction. We argue that an approach to olfactory function where information processing is emphasized could contribute to a high degree to our understanding of smell as a perceptual phenomenon emerging from neural computations. Further, we argue that combined analysis of the stimulus, biology, physiology, and behavior and perception can provide new insights into olfactory function. We hope that the reader can use this review as a competent guide and overview of research activities in olfactory physiology, psychophysics, computation, and psychology. We propose avenues for research, particularly in the systematic characterization of receptive fields and of perception.


Bariatric surgery is associated with a lower rate of death after myocardial infarction and stroke: A nationwide study.
To assess the potential protective effect of bariatric surgery on mortality after myocardial infarction (MI) or cerebrovascular accident (CVA). Using the National Inpatient Sample (2007-2014), 2218 patients with a principal discharge diagnosis of acute MI and 2168 patients with ischaemic CVA who also had history of prior bariatric surgery were identified. Utilizing propensity scores, these patients were matched 1:5 with patients who had similar principal diagnoses but no history of bariatric surgery (controls). Control group-1 included participants with obesity (BMI ≥ 35 kg/m2 ) only and participants in control group-2 were matched according to post-surgery BMI with the bariatric surgery group. The primary and secondary endpoints were in-hospital all-cause mortality and length of hospital stay, respectively. Outcomes after MI and CVA were separately compared among groups in multivariate regression models. A total of 48 300 (weighted) participants were included in the analysis. The distribution of covariates was well balanced after propensity matching. Mortality rates after MI were significantly lower in patients with a history of bariatric surgery compared with control group-1 (1.85% vs 3.03%; odds ratio (OR), 0.61; 95% confidence interval (CI), 0.44-0.86; P = 0.004) and with control group-2 (2.00% vs 3.26%; OR, 0.62; 95% CI, 0.44-0.88; P = 0.008). Similarly, in-hospital mortality rates after CVA were significantly lower in patients with a history of bariatric surgery compared with control group-1 (1.43% vs 2.74%; OR, 0.54; 95% CI, 0.37-0.79; P = 0.001) and with control group-2 (1.54% vs 2.59%; OR, 0.61; 95% CI, 0.41-0.91; P = 0.015). Furthermore, length of stay was significantly shorter in the bariatric surgery group for all comparisons (P < 0.001). Prior bariatric surgery is associated with significant protective effect on survival after MI and CVA.


Pregnancy and the Postpartum Period in Women With Relapsing-Remitting Multiple Sclerosis Treated With Old and New Disease-Modifying Treatments: A Real-World Multicenter Experience.
Introduction: Trends of disease activity during pregnancy, the postpartum period, and until 24 months from the delivery in the era of new drugs for the treatment of relapsing-remitting multiple sclerosis (RRMS) need to be investigated. Methods: In this cross-sectional Italian multicenter study, women with RRMS were included; the disease-modifying treatment (DMT) at the time of conception included were: interferons, glatiramer acetate, teriflunomide, dimethyl fumarate, fingolimod, and natalizumab. The main outcome of the study was to determine the rate of relapse occurrence during pregnancy and the postpartum period in all women grouped for each DMT. The secondary outcome was to determine the overall disease activity assessed by NEDA 3 (relapse, disability level, and radiological activity) at 24 months from the date of delivery. Results: Completed data were available for 81 pregnancies (in 74 women). Women on interferons and glatiramer had longer disease duration than women on dimethyl fumarate, fingolimod, and natalizumab (p < 0.05). Overall, we recorded 25 relapses during pregnancy (11 in 11 women) and the postpartum period (14 in 14 women). Natalizumab was the most commonly DMT in women (3) who experienced relapses during pregnancy. IFNs were the most commonly prescribed DMT in women (8) who experienced relapses during the postpartum period. At logistic regression analysis, specific treatment per se was not associated with relapse occurrence. No differences among the DMTs groups were recorded about NEDA 3 status at 24 months of follow-up. Conclusions: In our population, there was no difference in terms of relapses occurrence, disability status, and the overall disease activity during a follow up of 24 months.


Challenges in the delivery of peptide drugs: an industry perspective.
Due mainly to their poor stability and short plasma half-life, peptides are usually administered by injection, often several times daily. Injectable sustained-release formulations of peptides based on biodegradable polymer microparticles or implants early demonstrated the power of drug delivery technologies to enhance patient adherence and convenience, and increase safety and efficacy. Injectable sustained-release formulations are likely to remain a significant part of new peptide products. However, a new generation of technologies that enable solvent-free formulations and manufacturing processes, injection through narrow gauge needles and ready-to-use presentations will be increasingly used. In addition, the tremendous developments in noninvasive routes of delivery are likely to result in more and more peptides being delivered by the oral, transdermal, nasal or inhalation routes.


Attenuated Salmonella enterica Typhimurium reduces tumor burden in an autochthonous breast cancer model.
Cancer treatment with attenuated Salmonella enterica Typhimurium (S. Typhimurium) has gained momentum in recent years. However, the effectiveness of this treatment has not been explored in autochthonous models. We report the efficacy of S. Typhimurium in mice with autochthonous mammary tumors. S. Typhimurium attenuated by deletion of cyclic adenosine monophosphate signaling, SalpNG.1, was injected into female BALB-neuT tumor-bearing mice. Mice were monitored for efficacy and sacrificed for mechanistic studies. In treated mice, seven-week post-treatment tumor burden was reduced by 85% and median survival was increased by 88%. Efficacy was correlated with increased tumor-infiltrating CD8 and natural killer cells. In addition, SalpNG.1 treatment caused a systemic increase of monocytic myeloid-derived suppressor cells that accumulated to high numbers within tumor tissue. Bacteria were not detected in tumor tissue, suggesting that the observed efficacy was due to a systemic rather than a tumor-specific effect of the bacteria. S. Typhimurium treatment reduces tumor burden and increases survival in an autochthonous breast cancer model.


[Aortic stenosis: from diagnosis to optimal treatment].
Aortic stenosis is the most frequent valvular heart disease. Aortic sclerosis is the first characteristic lesion of the cusps, which is considered today as the process similar to atherosclerosis. Progression of the disease is an active process leading to forming of bone matrix and heavily calcified stiff cusps by inflammatory cells and osteopontin. It is a chronic, progressive disease which can remain asymptomatic for a long time even in the presence of severe aortic stenosis. Proper physical examination remains an essential diagnostic tool in aortic stenosis. Recognition of characteristic systolic murmur draws attention and guides further diagnosis in the right direction. Doppler echocardiography is an ideal tool to confirm diagnosis. It is well known that exercise tests help in stratification risk of asymptomatic aortic stenosis. Serial measurements of brain natriuretic peptide during a follow-up period may help to identify the optimal time for surgery. Heart catheterization is mostly restricted to preoperative evaluation of coronary arteries rather than to evaluation of the valve lesion itself. Currently, there is no ideal medical treatment for slowing down the disease progression. The first results about the effect of ACE inhibitors and statins in aortic sclerosis and stenosis are encouraging, but there is still not enough evidence. Onset symptoms based on current ACC/AHA/ESC recommendations are I class indication for aortic valve replacement. Aortic valve can be replaced with a biological or prosthetic valve. There is a possibility of percutaneous aortic valve implantation and transapical operation for patients that are contraindicated for standard cardiac surgery.


New C=C bond formation via nonstoichiometric titanium(IV) halide mediated vicinal difunctionalization of alpha,beta-unsaturated acyclic ketones
[reaction: see text] Highly stereoselective vicinal difuctionalization of alpha,beta-unsaturated ketones for the synthesis of multifunctionalized trisubstituted alkenes is described. The new reaction employs titanium(IV) halides (0.5 equiv) as promoters and inexpensive commercial chemicals as starting materials. The reaction can be performed at room temperature in a convenient vial without the protection of inert gases. Good to excellent yields and high Z/E stereoselectivity have been realized in most cases presented (16 examples).


Teaching multi-step requesting to children with autism spectrum disorder using systematic instruction and a speech-generating device.
The purpose of this study was to examine the effectiveness of an iPad-based speech-generating device (SGD) and an intervention package in teaching multi-step requesting to children with autism spectrum disorder (ASD). The intervention package comprised discrete trial teaching, time delay, graduated guidance, and reinforcement. Social validity data were also collected from parents and teachers. Three male participants with ASD, aged 4-5 years, participated in the study, which was conducted using a multiple-probe-across-participants design. Findings of the study showed that the SGD and the intervention package were effective in teaching multi-step requesting to all participants. Furthermore, the target skill was maintained and generalized to different materials and individuals. Social validity findings indicated that opinions of the mothers and teachers were positive. On the other hand, the father of one participant stated that he was concerned with possible negative effects of using tablet computers. The findings are discussed with regard to the parents' opinions, and implications for practice and research.


Insulin promotes rapid delivery of N-methyl-D- aspartate receptors to the cell surface by exocytosis.
Insulin potentiates N-methyl-d-aspartate receptors (NMDARs) in neurons and Xenopus oocytes expressing recombinant NMDARs. The present study shows that insulin induced (i) an increase in channel number times open probability (nP(o)) in outside-out patches excised from Xenopus oocytes, with no change in mean open time, unitary conductance, or reversal potential, indicating an increase in n and/or P(o); (ii) an increase in charge transfer during block of NMDA-elicited currents by the open channel blocker MK-801, indicating increased number of functional NMDARs in the cell membrane with no change in P(o); and (iii) increased NR1 surface expression, as indicated by Western blot analysis of surface proteins. Botulinum neurotoxin A greatly reduced insulin potentiation, indicating that insertion of new receptors occurs via SNARE-dependent exocytosis. Thus, insulin potentiation occurs via delivery of new channels to the plasma membrane. NMDARs assembled from mutant subunits lacking all known sites of tyrosine and serine/threonine phosphorylation in their carboxyl-terminal tails exhibited robust insulin potentiation, suggesting that insulin potentiation does not require direct phosphorylation of NMDAR subunits. Because insulin and insulin receptors are localized to glutamatergic synapses in the hippocampus, insulin-regulated trafficking of NMDARs may play a role in synaptic transmission and plasticity, including long-term potentiation.


[Educational differences in health care utilization in the last year of life among South Korean cancer patients].
There have been few studies examining the differences in health care utilization across social classes during the last year of life. Therefore, in this study we analyzed the quantitative and qualitative differences in health care utilization among cancer patients across educational classes in their last year of life, and derived from it implications for policy. To evaluate health care utilization by cancer patients in the last year of life, Death certificate data from 2004 were merged with National Health Insurance data (n = 60,088). In order to use educational level as a social class index, we selected the individuals aged 40 and over as study subjects (n = 57,484). We analyzed the differences in the medical expenditures, admission days, and rates of admission experience across educational classes descriptively. Multiple regression analysis was conducted to evaluate the association between medical expenditures and independent variables such as sex, age, education class, site of death and type of cancer. The upper educational class spent much more on medical expenditures in the last one year of life, particularly during the last month of life, than the lower educational class did. The ratio of monthly medical expenditures per capita between the college class and no education class was 2.5 in the last 6-12 months of life, but the ratio was 1.6 in the last 1 month. Also, the lower the educational class, the higher the proportion of medical expenditures during the last one month of life, compared to total medical expenditures in the last one year of life. The college educational class had a much higher rate of admission experiences in tertiary hospitals within Seoul than the other education classes did. This study shows that the lower educational classes had qualitative and quantitative disadvantages in utilizing health care services for cancer in the last year of life.


Cofactor Controlled Encapsulation of a Rhodium Hydroformylation Catalyst.
Supramolecular approaches in transition-metal catalysis, including catalyst encapsulation, have attracted considerable attention. Compared to enzymes, supramolecular catalysts in general are less complex. Enzyme activity is often controlled by the use of smaller cofactor molecules, which is important in order to control reactivity in complex mixtures of molecules. Interested in increasing complexity and allowing control over supramolecular catalyst formation in response to external stimuli, we designed a catalytic system that only forms an efficient supramolecular complex when a small cofactor molecule is added to the solution. This in turn affects both the activity and selectivity when applied in a hydroformylation reaction. This contribution shows that catalyst encapsulation can be controlled by the addition of a cofactor, which affects crucial catalyst properties.


Development of a taxonomy of unprofessional behavior in clinical learning environments using learner-generated critical incidents.
Few studies have examined medical residents' and fellows' (trainees) direct experience of unprofessional behavior in clinical learning environments (CLE). The purpose of this study was to create a taxonomy of unprofessional behavior in CLEs using critical incidents gathered from trainees. In step 1 (data collection), the authors collected 382 critical incidents from trainees at more than a dozen CLEs over a six-year period (2013-2019). In step 2 (model generation), nine subject matter experts (SMEs) sorted the incidents into homogenous clusters and this structure was tested with principal components analysis (PCA). In step 3 (model evaluation), two new groups of SMEs each re-sorted half of the incidents into the PCA-derived categories. A 13-component solution accounted for 62.46% of the variance in the critical incidents collected. The SMEs who re-sorted the critical incidents demonstrated good agreement with each other and with the 13-component PCA solution. The resulting taxonomy included 13 dimensions, with 48.7% of behaviors focused on displays of aggression or discriminatory conduct. Critical incident methodology can provide unique insights into the dimensionality of unprofessional behavior in the CLE. Future research should leverage the taxonomy created to inform professionalism assessment development in the CLE.


Somatosensory evoked high-frequency oscillations reflecting thalamo-cortical activity are decreased in migraine patients between attacks.
A deficit of habituation in cortical information processing, including somatosensory evoked potentials (SSEPs), is the most consistent neurophysiological abnormality in migraine patients between attacks. To explore further the mechanisms underlying this interictal neural dysfunction, we have studied the high-frequency oscillations (HFOs) embedded in SSEPs because they are thought to reflect spike activity in thalamo-cortical cholinergic fibres (early HFOs) and in cortical inhibitory GABAergic interneurons (late HFOs). Untreated migraine patients with (MA) and without (MO) aura were recorded during (n = 13: nine MO, four MA) and between attacks (n = 29: 14 MO, 15 MA) and compared with healthy volunteers. SSEPs were filtered off-line (digital band-pass between 450 and 750 Hz) to extract the two HFO bursts from the broad-band contralateral N20 somatosensory cortical response obtained by median nerve stimulation. In both migraine groups, amplitudes and latencies of conventional broad-band SSEPs recorded interictally from cervical and parietal active electrodes were not significantly different from those found in healthy volunteers. In contrast, maximum peak-to-peak amplitude and area under the rectified curve of the early HFO burst were significantly smaller in both MA and MO patients than in healthy volunteers. There was no significant difference in the later HFO burst between migraineurs and healthy volunteers. During attacks, all electrophysiological measurements in migraineurs were similar to those found in healthy volunteers. Thalamo-cortical activation, as reflected by the early SSEP HFO burst, may thus be reduced in migraine interictally, but normalizes during an attack, whereas intracortical inhibition, as indexed by the late HFO burst, is normal at any time. This supports the hypothesis that the habituation deficit in migraineurs is due to a reduced pre-activation level of sensory cortices and not to increased cortical excitability or reduced intracortical inhibition.


Genomic and Phenotypic Diversity among Ten Laboratory Isolates of Pseudomonas aeruginosa PAO1.
Pseudomonas aeruginosa is an opportunistic pathogen found ubiquitously in the environment and commonly associated with airway infection in patients with cystic fibrosis. P. aeruginosa strain PAO1 is one of the most commonly used laboratory-adapted research strains and is a standard laboratory-adapted strain in multiple laboratories and strain banks worldwide. Due to potential isolate-to-isolate variability, we investigated the genomic and phenotypic diversity among 10 PAO1 strains (henceforth called sublines) obtained from multiple research laboratories and commercial sources. Genomic analysis predicted a total of 5,682 genes, with 5,434 (95.63%) being identical across all 10 strains. Phenotypic analyses revealed comparable growth phenotypes in rich media and biofilm formation profiles. Limited differences were observed in antibiotic susceptibility profiles and immunostimulatory potential, measured using heat-killed whole-cell preparations in four immortalized cell lines followed by quantification of interleukin-6 (IL-6) and IL-1β secretion. However, variability was observed in the profiles of secreted molecular products, most notably, in rhamnolipid, pyoverdine, pyocyanin, Pseudomonas quinolone signal (PQS), extracellular DNA, exopolysaccharide, and outer membrane vesicle production. Many of the observed phenotypic differences did not correlate with subline-specific genetic changes, suggesting alterations in transcriptional and translational regulation. Taken together, these results suggest that individually maintained sublines of PAO1, even when acquired from the same parent subline, are continuously undergoing microevolution during culture and storage that results in alterations in phenotype, potentially affecting the outcomes of in vitro phenotypic analyses and in vivo pathogenesis studies.IMPORTANCE Laboratory-adapted strains of bacteria are used throughout the world for microbiology research. These prototype strains help keep research data consistent and comparable between laboratories. However, we have observed phenotypic variability when using different strains of Pseudomonas aeruginosa PAO1, one of the major laboratory-adopted research strains. Here, we describe the genomic and phenotypic differences among 10 PAO1 strains acquired from independent sources over 15 years to understand how individual maintenance affects strain characteristics. We observed limited genomic changes but variable phenotypic changes, which may have consequences for cross-comparison of data generated using different PAO1 strains. Our research highlights the importance of limiting practices that may promote the microevolution of model strains and calls for researchers to specify the strain origin to ensure reproducibility.


Efficacy of combined immunostimulation and chemotherapy in experimental visceral Leishmaniasis.
A regimen of combined immunostimulation and chemotherapy for the elimination of Leishmania donovani amastigotes was evaluated. An in vitro experimental model utilized cultured peritoneal macrophages from C57B1/6 mice infected with L. donovani tissue forms. Partial or complete activation of macrophages as judged by killing of tumor cells significantly enhanced the efficacy of sodium antimony gluconate (Pentostam). The quantity of drug required for elimination of parasites from immunostimulated cells was considerably lower than that required to achieve comparable amastigote killing in thioglycolate-elicited macrophages. In contrast, amphotericin B cleared infected cells of amastigotes at comparable drug levels when tested with immunostimulated and unstimulated macrophages. Several drugs tested inhibited the conversion of amastigotes to promastigotes in vitro but were ineffective in killing of intracellular tissue forms. Allopurinol and difluoromethylornithine (DMFO) blocked amastigote conversion significantly. These drugs at high concentrations, however, exerted only minimal toxicity for amastigotes residing within macrophages. Efficacy of combined therapy was also demonstrated in vivo. Immunoenhancement of L. donovani-infected mice with Corynebacterium parvum vaccine combined with a regimen of sodium antimony gluconate was significantly more effective than was immunotherapy or drug therapy alone.


Heterogeneity in kinesin function.
The kinesin family proteins are often studied as prototypical molecular motors; a deeper understanding of them can illuminate regulation of intracellular transport. It is typically assumed that they function identically. Here we find that this assumption of homogeneous function appears incorrect: variation among motors' velocities in vivo and in vitro is larger than the stochastic variation expected for an ensemble of "identical" motors. When moving on microtubules, slow and fast motors are persistently slow, and fast, respectively. We develop theory that provides quantitative criteria to determine whether the observed single-molecule variation is too large to be generated from an ensemble of identical molecules. To analyze such heterogeneity, we group traces into homogeneous sub-ensembles. Motility studies varying the temperature, pH and glycerol concentration suggest at least 2 distinct functional states that are independently affected by external conditions. We end by investigating the functional ramifications of such heterogeneity through Monte-Carlo multi-motor simulations.


Validation and calibration of a model used to reconstruct historical exposure to polycyclic aromatic hydrocarbons for use in epidemiologic studies.
We previously developed a historical reconstruction model to estimate exposure to airborne polycyclic aromatic hydrocarbons (PAHs) from traffic back to 1960 for use in case-control studies of breast cancer risk. Here we report the results of four exercises to validate and calibrate the model. Model predictions of benzo[a]pyrene (BaP) concentration in soil and carpet dust were tested against measurements collected at subjects' homes at interview. In addition, predictions of air intake of BaP were compared with blood PAH-DNA adducts. These same soil, carpet, and blood measurements were used for model optimization. In a separate test of the meteorological dispersion part of the model, predictions of hourly concentrations of carbon monoxide from traffic were compared with data collected at a U.S. Environmental Protection Agency monitoring station. The data for soil, PAH-DNA adducts, and carbon monoxide concentrations were all consistent with model predictions. The carpet dust data were inconsistent, suggesting possible spatial confounding with PAH-containing contamination tracked in from outdoors or unmodeled cooking sources. BaP was found proportional to other PAHs in our soil and dust data, making it reasonable to use BaP historical data as a surrogate for other PAHs. Road intersections contributed 40-80% of both total emissions and average exposures, suggesting that the repertoire of simple markers of exposure, such as traffic counts and/or distance to nearest road, needs to be expanded to include distance to nearest intersection.


Microtubules and root protophloem ontogeny in wheat.
Protophloem ontogeny in roots of Triticum aestivum has been investigated ultrastructurally. Each protophloem pole consists of three cells, a protophloem sieve element and two companion cells, all originating from a single precursor cell usually having a pentahedral shape. This protophloem mother cell (PMC) undergoes two successive asymmetrical divisions: the first one gives rise to a smaller cell that will differentiate into a companion cell, and a larger one that divides again asymmetrically yielding another companion cell and a protophloem sieve element. The latter divides once more, but now symmetrically, increasing the number of cells. Both asymmetrical and symmetrical divisions are preceded by preprophase microtubule bands (PMBs), well demarcated by a great number (more than 100 profiles in a single band section) of microtubules (MTs). The plane of a PMB coincides with that of the succeeding cell plate, which fuses with parent walls at sites previously occupied by the PMB. The strict correspondence between PMB and cell plate suggests that a cytokinesis the latter bisects the PMB cortical zone. The possible role of PMB cortical zone in positioning the cell plate and guiding its expanding edges towards predetermined sites is discussed in relation to recent discoveries in other anatomical situations. The plane of PMBs (and hence of divisions) changes from one division to the next, so that the three successive divisions occur in three spatial planes transversely to each other. This change is probably influenced by cell polarity. Prior to each asymmetrical division peri-nuclear MTs were observed besides the MTs of the PMB. They appear before the PMB organization and persist throughout preprophase, but they change their position and orientation in response to the transition from PMB to the spindle organization.


Effect of endurance exercise on hepatic lipid content, enzymes, and adiposity in men and women.
Obesity and physical inactivity are independent risk factors for the development of nonalcoholic fatty liver disease (NAFLD). We determined the effect of endurance exercise training on hepatic lipid content and hepatic enzyme concentration in men and women. Waist circumference (WC), percent body fat (BF), computed tomography (CT) scans for liver attenuation (inverse relationship with hepatic lipid), bilirubin, alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) plasma concentrations were measured before and after 12 weeks of endurance training in 41 lean and obese men and women. Exercise training did not change liver attenuation, body weight, percent BF, bilirubin, or ALT concentration, but did lower WC (P < 0.0001), and decreased GGT in men only (P = 0.01). Obese subjects had a lower liver attenuation than lean subjects (P = 0.04). Obese women had lower ALT than obese men (P = 0.03). GGT was lower in women before and after training. WC was positively correlated with GGT (r = 0.32, P = 0.003) and ALT (r = 0.320, P = 0.004) and negatively correlated with liver attenuation (r = -0.340, P = 0.03). Percent BF was negatively correlated with bilirubin (r = -0.374, P = 0.005). Liver attenuation was negatively correlated with ALT (r = -0.405, P = 0.003). Short-term endurance training without weight loss does not alter hepatic lipid content. There was a strong relationship between GGT/ALT and body composition (percent BF) as well as between ALT and hepatic lipid content.


Effects of Rehearsal Time and Repertoire Speed on Extensor Carpi Radialis EMG in Conservatory Piano Students.
Repetitive actions while playing piano may overload forearm muscles and tendons, leading to playing-related musculoskeletal disorders (PRMDs), including lateral epicondylitis. In this pilot study, surface electromyography (sEMG) activity of the extensor carpi radialis (ECR) was captured in 10 conservatory piano students while playing a fast and a slow music score selected from the individual's repertoire, each 3 minutes long. Measurements were made at baseline and again after 2 hrs and 4 hrs of rehearsal time of the piano études. The amplitude of the sEMG signal was processed by a smoothing algorithm, and the frequency component with a non-orthogonal wavelets procedure. Amplitude of the sEMG was expressed in percent of maximal voluntary contraction (%MVC) at baseline. Statistical analysis encompassed 2-way repeated measures ANOVAs for the amplitude and frequency components of the sEMG signal (a set at 5%). The students also rated the intensity of rehearsals using a VAS. The ECR presented with a mean amplitude of 23%MVC for the slow scores, which increased significantly to 36%MVC for the fast scores. The sEMG signal presented a significant though small decrease of 1.9%MVC in amplitude between baseline and 4 hrs of rehearsal time and no shift in frequency, which may indicate that the rehearsals were held at a physiological steady-state and suggesting optimization or complementary muscle loading. These data accentuated that the loading of the ECR (as reflected in the amplitude component) was higher than that seen for computer keyboard workers. The augmented loading of the ECR and reduced blood flow to forearm muscles may be a factor in the development of PRMDs in pianists.


Clinical significance of LAIR1 (CD305) as assessed by flow cytometry in a prospective series of patients with chronic lymphocytic leukemia.
Most patients affected by chronic lymphocytic leukemia are diagnosed by flow cytometry. Several immunophenotypic markers have been identified as significant and independent prognostic variables, especially from retrospective cohorts. However, while attractive because their detection is inexpensive and feasible in most laboratories, only few have been validated by independent series. The expression of leukocyte-associated immunoglobulin-like receptor-1 (also known as LAIR1, LAIR-1 or CD305), an inhibitor of B-cell receptor-mediated signaling, has been reported to be lacking in high-risk chronic lymphocytic leukemia. However, its correlation with biological variables and its prognostic significance remain unknown. We investigated 311 consecutive patients, prospectively enrolled since 2007. Methods for studying patients were standardized and included clinical assessment, immunophenotype, fluorescence in situ hybridization, and status of immunoglobulin heavy chain variable region genes. Overall, 22.1% of patients had Binet stage B or C disease, 38.5% had unmutated immunoglobulin genes, 15.1% had high-risk cytogenetic abnormalities, 23.4% were CD38(+), 37.8% CD49d(+), and 59.8% LAIR1(+). Expression of LAIR1 was inversely related to that of CD38 (P=0.0005), but was not associated with CD49d expression (P=0.96). A significantly lower expression of LAIR1 was observed in patients with Binet stage B or C disease (P=0.023), and in the presence of high-risk cytogenetic abnormalities (P=0.048) or unmutated immunoglobulin heavy chain variable region genes (P<0.0001). At univariate analysis LAIR1(+) was significantly associated with longer time to first treatment (P=0.0002). This favorable effect of LAIR1(+) was confirmed by multivariate analysis (hazard ratio=2.1, P=0.03 for LAIR1). Our results indicate that LAIR1 expression is a reliable and inexpensive marker capable of independently predicting time to first treatment in newly diagnosed unselected patients with chronic lymphocytic leukemia.


Retroperitoneal fibrosis in the military hospital of Morocco.
Retroperitoneal fibrosis (RPF) is a rare disease. It is characterized by the presence of fibro-inflammatory tissue involving retroperitoneal structures. The usual mode of presentation of this disease is with lumbar pain, kidney failure, and a biological inflammatory syndrome. The aim of our study is to describe the diagnostic, etiologic, therapeutic aspects and outcomes of RPF in a nephrology unit in Morocco. Twelve cases of RPF were included in our study. The mean age was 57 ± 10 years (32.70). Nine patients were male and three were female. Symptoms were highly variable, dominated by pain that was present in all patients. Venous compressive signs were described in four patients (33.3%), anuria in one patient (8.3%), and hematuria in two patients (16.6%). Laboratory examinations found an inflammatory syndrome in all patients and renal failure in nine patients (75%), with a mean serum creatinine at 35 mg/L ± 8.5. Diagnosis was suspected on the ultrasound data and confirmed by computed tomography or magnetic resonance imaging. RPF was idiopathic in nine patients (75%). It was secondary to aortic aneurysm in one patient (8.3%), Riedel's thyroiditis in one patient (8.3%), and drug induced in another patient (8.3%). All patients received surgical treatment along with corticosteroids. At six months, remission was achieved in nine patients, whereas three others had steroid resistance. These patients were treated by mycophenolate mofetil (MMF) at a dose of 2 g/day; two of them had intestinal intolerance to MMF and thus were treated by tamoxifen at a dose of 40 mg/day. At 24 months, they stabilized their renal function with incomplete regression of the fibrotic plate. No cases of recurrence were observed during the study period.


[Professional confidentiality of the physician].
Summarizing it is to be mentioned that, concerning the professional secrecy, the principle is held that the physician is allowed to speak as much as it is necessary and he must be silent as far as it is possible. The physician is entitled to reveal but not obliged to do so as far as he has been exonerated from the professional secrecy or as far as the revelation is necessary for the protection of a higher legal proceeding. This is taken into consideration also for evidence in judicial proceedings. Apart from legal informational obligations at first, however, not the physician but the patient defines the breadth of allowable infringements. Only when the professional secrecy collides with the legal matters of third persons the physician himself gets into compulsions of decision. Taking into consideration the criminal law the maintenance as well as the infringement of the professional secrecy remain without consequences for the physician, if the translegal critical state is present. In such cases, however, he should endeavour to keep the dangers which brings his silence for others as insignificant as possible.


Purification and characterization of the beta-adrenergic receptor kinase.
The beta-adrenergic receptor kinase (beta-ARK) is a recently discovered enzyme which specifically phosphorylates the agonist-occupied form of the beta-adrenergic receptor (beta-AR) as well as the light-bleached form of rhodopsin. beta-ARK is present in a wide variety of mammalian tissues. The kinase can be purified from bovine cerebral cortex to greater than 90% homogeneity by sequential chromatography on Ultrogel AcA34, DEAE-Sephacel, CM-Fractogel, and hydroxylapatite. This results in an approximately 20,000-fold purification with an overall recovery of 12%. The purified kinase has an Mr approximately 80,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Several findings indicate that this peptide contains the beta-ARK activity. First, on hydroxylapatite chromatography the enzyme activity coelutes with the Mr approximately 80,000 protein as revealed by Coomassie-Blue staining. Second, under phosphorylating conditions the Mr approximately 80,000 protein is phosphorylated. Finally, the Mr approximately 80,000 protein specifically interacts with reconstituted agonist-occupied beta-AR. Kinetic parameters of the enzyme for beta-AR are Km = 0.25 microM and Vmax = 78 nmol/min/mg whereas for rhodopsin the values are Km = 6 microM and Vmax = 72 nmol/min/mg. The Km value of the enzyme for ATP is approximately 35 microM using either beta-AR or rhodopsin as substrate. Receptor phosphorylation by beta-ARK is effectively inhibited by Zn2+, digitonin and a variety of salts. The availability of purified beta-ARK should greatly facilitate studies of its role in receptor desensitization.


Association of NLRPs with pathogenesis of dry age-related macular degeneration.
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population, and Dry AMD is the most common clinical subtype. However, effective measures for the early diagnosis and treatment of dry AMD have not been proposed. In recent years, NOD-like receptors (NLRs) have received attention in the study of AMD as an important class of pattern recognition receptors. We attempted to elucidate the pathogenesis of NLRs in dry AMD from the perspective of chronic inflammation. This study involved 13 patients with dry AMD, 10 age- and sex-matched normal population without any history of disease and 8 patients with wet AMD as controls. Using RT-qPCR, the mRNA expression levels of NLRs in peripheral blood peripheral blood mononuclear cells (PBMCs) were compared to analyze the statistical differences in the expression contents among the three populations. The relative RNA expression of nucleotide-binding oligomerization-like receptor protein 12 (NLRP12) with negative regulation of inflammation was significantly lower in dry AMD patients than in normal people and wet AMD patients. And NLRX1, which also has an anti-inflammatory effect, was lower in dry AMD patients than in wet AMD patients. However, NLRP3 with proinflammatory effect was significantly expressed in wet AMD. The significant decrease in NLRP12 in dry AMD may become a breakthrough in the study of dry AMD and systemic chronic inflammatory response. However, NLRP3 may have a more important role in wet AMD.


Attention-Deficit Hyperactivity Disorder (ADHD) and narrative discourse in older adults.
Attention-Deficit Hyperactivity Disorder (ADHD) encompasses other symptoms besides inattention, hyperactivity, and impulsivity, such as language problems. ADHD can have a non-remitting course and is also found in older individuals, although there are no studies on language problems in elderly individuals with the disorder. To investigate the presence of language impairment in older adults with ADHD. Language impairment was investigated in three older ADHD adults, and compared with two matched control subjects using a narrative discourse task. The transcript discourses were evaluated based on the Trabasso Model for discourse analysis, and then processed by the Speech Graph Analysis software. Compared to control subjects, ADHD patient discourse had more Plot components and their networks exhibited more Edges. The patients had higher scores on the Narrative Inefficiency, Density and Diameter Indexes as well as on the Average Clustering Coefficient. The networks of control subjects were sequential, with little or no recursiveness, whereas those of ADHD subjects were convoluted. Our results suggest that language deficits described in children, adolescents and young adults with ADHD may persist in older adults with the disorder.


Domain independent post-processing with graph U-nets: applications to electrical impedance tomographic imaging.
To extend the highly successful U-Net Convolutional Neural Network architecture, which is limited to rectangular pixel/voxel domains, to a graph-based equivalent that works flexibly on irregular meshes; and demonstrate the effectiveness on Electrical Impedance Tomography (EIT). By interpreting the irregular mesh as a graph, we develop a graph U-Net with new cluster pooling and unpooling layers that mimic the classic neighborhood based max-pooling important for imaging applications. Main~Results: The proposed graph U-Net is shown to be flexible and effective for improving early iterate Total Variation (TV) reconstructions from EIT measurements, using as little as the first iteration. The performance is evaluated for simulated data, and on experimental data from three measurement devices with different measurement geometries and instrumentations. We successfully show that such networks can be trained with a simple two-dimensional simulated training set, and generalize to very different domains, including measurements from a three-dimensional device and subsequent 3D reconstructions. As many inverse problems are solved on irregular (e.g. finite element) meshes, the proposed graph U-Net and pooling layers provide the added flexibility to process directly on the computational mesh. Post-processing an early iterate reconstruction greatly reduces the computational cost which can become prohibitive in higher dimensions with dense meshes. As the graph structure is independent of `dimension', the flexibility to extend networks trained on 2D domains to 3D domains offers a possibility to further reduce computational cost in training.


Taxonomy of Adaptive Neuro-Fuzzy Inference System in Modern Engineering Sciences.
Adaptive Neuro-Fuzzy Inference System (ANFIS) blends advantages of both Artificial Neural Networks (ANNs) and Fuzzy Logic (FL) in a single framework. It provides accelerated learning capacity and adaptive interpretation capabilities to model complex patterns and apprehends nonlinear relationships. ANFIS has been applied and practiced in various domains and provided solutions to commonly recurring problems with improved time and space complexity. Standard ANFIS has certain limitations such as high computational expense, loss of interpretability in larger inputs, curse of dimensionality, and selection of appropriate membership functions. This paper summarizes that the standard ANFIS is unsuitable for complex human tasks that require precise handling of machines and systems. The state-of-the-art and practice research questions have been discussed, which primarily focus on the applicability of ANFIS in the diversifying field of engineering sciences. We conclude that the standard ANFIS architecture is vastly improved when amalgamated with metaheuristic techniques and further moderated with nature-inspired algorithms through calibration and tuning of parameters. It is significant in adapting and automating complex engineering tasks that currently depend on human discretion, prominent in the mechanical, electrical, and geological fields.


[Hormonal profile in chronic pain syndromes of somatogenic etiology].
The integral "profile" of the groups of inpatients suffering from somatogenic chronic painful syndromes was plotted on a material of a comprehensive study into central and peripheral hormones, the total content, and correlations. Enkephalins are shown to play the integrating part in the development of stress-algogenic reactions.


The value of transthoracic echocardiography and chest X-ray in locating the tip of central venous catheter in dialysis patients: a comparative study with computed tomography imaging.
To determine the tip position of the central venous catheter (CVC) in patients with dialysis, the guidelines recommend that it be determined using chest radiography (CXR) after catheterization, without fluoroscopy. However, some researchers have proposed that transthoracic echocardiography (TTE) can replace CXR, but this has not been widely adopted. This study aimed to determine which of the two aforementioned methods is more suitable for locating the tip position of the CVC. This prospective study included 160 patients who underwent hemodialysis at our hospital from March 2021 to December 2022. After inserting the CVC through the internal jugular vein, we used transthoracic echocardiography and CXR to determine the tip of the CVC and compared the results with those of computed tomography (CT). In the comparison between TTE and CXR for locating the CVC tip, we obtained three main findings. (1) TTE was associated with fewer misdiagnosed cases than CXR. (2) TTE provided higher sensitivity (similar sensitivity in position 2), specificity, positive/negative predictive values, and accuracy than CXR. (3) When comparing the receiver operating characteristic curves of TTE and CXR, the area under the curve (95% confidence interval) for the former was larger. Additionally, we made anatomical discoveries: the "hyperechoic triangle" recognized by TTE was equivalent to the entrance of the superior vena cava into the right atrium shown by transesophageal transthoracic echocardiography. TTE is more suitable than CXR as the first examination for CVC tip localization, as it improves diagnostic accuracy and reduces X-ray radiation damage.


Fibronectin increases matrix metalloproteinase 9 expression through activation of c-Fos via extracellular-regulated kinase and phosphatidylinositol 3-kinase pathways in human lung carcinoma cells.
Enhanced expression of matrix metalloproteinase-9 (MMP-9) is associated with human lung tumor invasion and/or metastasis. We have demonstrated that fibronectin (FN), a matrix glycoprotein, stimulates human non-small cell lung carcinoma (NSCLC) cell proliferation. The current study examines the effect of FN on MMP-9 expression in NSCLC cells. We show that FN increases MMP-9 protein, mRNA expression, and gelatinolytic activity in NSCLC cells. The integrin alpha5beta1 mediated the effects of FN because alpha5 small interfering RNA blocked FN-stimulated MMP-9 protein expression, and also abrogated FN-induced phosphorylation of ERK and phosphatidylinositol 3-kinase (PI3K) signals. The inhibitor of ERK, PD98095, and of PI3K, wortmannin, but not that of protein kinase A, H89, of Rho kinase, Y-27632, of mTOR, rapamycin, or of JNK, SP600125, prevented FN-induced MMP-9 gelatinolytic activity and gene expression. FN enhanced MMP-9 gene promoter activity; however, there was no response to FN in DNA constructs with an AP-1 site mutation. FN increased AP-1 DNA binding activity, and this was abrogated by cyclic AMP response element decoy oligonucleotides, which also diminished FN-induced MMP-9 promoter activity. FN increased the expression of the AP-1 subunit c-Fos protein, but not in the presence of PD98095 and wortmannin. The AP-1 inhibitor, nordihydroguaiaretic acid, and a c-Fos small interfering RNA eliminated the effect of FN on MMP-9 expression. This study indicates that FN, by binding to the integrin alpha5beta1 receptor, stimulates the expression of MMP-9 through increased AP-1/DNA binding and c-Fos protein expression via ERK and PI3K signaling pathways. The data unveils a novel mechanism by which FN could promote NSCLC cell invasion and metastasis.


Expression of smooth muscle markers in so called malignant fibrous histiocytomas.
To obtain further information regarding the frequency and degree of positivity for smooth muscle markers in a large number of malignant fibrous histiocytomas (MFHs), as an aid to accurate diagnosis. The immunohistochemical features of 100 MFHs were studied and the results were compared with those for 30 leiomyosarcomas. Eighteen cases of MFH with smooth muscle actin (SMA) positivity were examined ultrastructurally. Immunoreactivity for smooth muscle markers, such as desmin, SMA, muscle specific actin (MSA) and h-caldesmon (HCD), which is a specific marker for smooth muscle cells and their tumours, was found in 28, 30, 29, and 29 of 30 leiomyosarcomas. Immunoreactivity for desmin, SMA, MSA, and HCD was found in 17, 30, 14, and two of the MFHs. On electron microscopic examination, approximately half of the cases contained a varying proportion of myofibroblastic cells. The others had only fibroblastic or undifferentiated tumour cells. At least 30% of the cases were found to display features consistent with limited smooth muscle or myofibroblastic differentiation. A large subset of so called MFH in fact shows poorly differentiated smooth muscle or myofibroblastic features, and perhaps such tumours should be regarded as pleomorphic leiomyosarcomas and/or pleomorphic myofibroblastic sarcomas.


Randomised clinical trial of patient satisfaction with traditional and simplified complete dentures.
To clinically evaluate the patient satisfaction and associated costs of dentures made using a simplified procedure that eliminates assembly on the articulator and dentures made with the conventional technique. Single-blind randomised clinical trial. Forty edentulous patients were randomly divided into 2 groups. One group received dentures made using the conventional method (CG), and the other using a simplified technique (SG) that omits the use of functional impressions (with modelling compound and ZOE impression paste) and an articulator to assemble the models. Overall patient satisfaction was assessed at 3 and 6 months by means of a Numerical Rating Scale (NRS). The comparisons were made using a repeated measures ANOVA (P = .05). No significant differences were found in terms of the satisfaction stated by the patients or the quality of the prosthesis evaluated by a professional among the dentures made using the traditional (n = 17) and simplified (n = 21) techniques. The rehabilitation of an edentulous patient with a simplified technique for the preparation of a total prosthesis is a feasible, more economical alternative and accepted by most patients.


Smoking is associated with first-ever incidence of mental disorders: a prospective population-based study.
It is well established that tobacco use is associated with mental disorders. However, the association between tobacco use and mental disorders has not yet been examined sufficiently in prospective, population-based studies. The current study is aimed at examining whether smoking is associated with first-ever incidence of mental disorders. We conducted a prospective, population-based epidemiological study (the Netherlands Mental Health Survey and Incidence Study: NEMESIS) in which a representative sample of adults aged 18-64 years (n = 7076) were interviewed to establish the presence of a broad range of mental disorders. We re-interviewed them at 1 year (n = 5618; response 79.4%) and 3 years (n = 4796; 67.8%) after baseline. The presence of mental disorders was assessed according to DSM-III-R criteria with the Composite International Diagnostic Interview (CIDI), which was administered by trained lay interviewers. Tobacco use was assessed by asking respondents whether they had smoked in the past year, and how many cigarettes they smoked. Subjects who smoked but never had a mental disorder in their life, had an increased risk of developing a mental disorder (P < 0.01), and this remained significant after correcting for major risk indicators of mental disorders. Smoking is associated not only with the prevalence, but also with first-ever incidence of mental disorders. More research is needed to study the causal pathways.


Inhibition of interleukin 6-mediated mitogen-activated protein kinase activation attenuates growth of a cholangiocarcinoma cell line.
Biliary tract malignancies represent challenges because of the lack of effective therapy and poor prognosis, in part because of the paucity of information regarding the mechanisms regulating their growth. We have recently identified a critical role for the p44/p42 mitogen-activated protein kinase (MAPK) pathway in interleukin 6 (IL-6)-stimulated growth of human cholangiocytes. Although IL-6 is a potential mitogen for cholangiocarcinoma, the role of this cytokine and its intracellular signaling pathways in cholangiocarcinoma growth is unknown. Thus, our aims were to determine the role of IL-6-mediated signaling mechanisms, and in particular the MAPK pathways, in the growth regulation of human cholangiocarcinoma. KMCH-1 cells (malignant cholangiocyte cells) secreted IL-6 constitutively, and increased IL-6 secretion in response to inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and IL-1beta. Stimulation with IL-6 resulted in proliferation of malignant cholangiocytes. These cells also possessed the IL-6 receptor complex subunits as directly assessed by immunoblot analysis. Furthermore, proliferation was completely inhibited by preincubation with anti-IL-6 neutralizing antibodies, indicating that the proliferative response to IL-6 involved receptor-mediated signaling. Both p38 and p44/p42 MAPKs were constitutively present and active in malignant cholangiocytes, and increased activity of both was observed within 15 minutes of stimulation with IL-6. Selective inhibition of either the p44/p42 MAPK pathway, by PD098059, or of the p38 MAPK pathway, by SB203580, blocked proliferation in response to IL-6. Thus, IL-6 can contribute to the autocrine and/or paracrine growth stimulation of malignant cholangiocytes via activation of either p38 or p44/p42 MAPK signaling pathways.


Role of spinal astrocytes through the perisynaptic astrocytic process in pathological pain.
Pathological pain is caused by abnormal activity in the neural circuit that transmits nociceptive stimuli. Beyond homeostatic functions, astrocytes actively participate in regulating synaptic transmission as members of tripartite synapses. The perisynaptic astrocytic process (PAP) is the key structure that allows astrocytes to play these roles and not only physically supports synapse formation through cell adhesion molecules (CAMs) but also regulates the efficiency of chemical signaling. Accumulating evidence has revealed that spinal astrocytes are involved in pathological pain by modulating the efficacy of neurotransmitters such as glutamate and GABA through transporters located in the PAP and by directly regulating synaptic transmission through various gliotransmitters. Although various CAMs contribute to pathological pain, insufficient evidence is available as to whether astrocytic CAMs also have this role. Therefore, more in-depth research is needed on how pathological pain is induced and maintained by astrocytes, especially in the PAP surrounding the synapse, and this will subsequently increase our understanding and treatment of pathological pain.


Assessment of health impacts and costs attributable to air pollution in urban areas using two different approaches. A case study in the Western Balkans.
In this study, two different air quality impact assessment methodologies were adopted and combined with a sensitivity analysis to estimate the unit costs. Air pollution health impact (mortality) assessment was carried out using one methodology based on log-linear concentration response functions (CRF) and another relying on the integrated exposure response curve (IER) from the Global Burden of Disease. Morbidity impacts were estimated with the CRF approach only. To assess the inequalities between low and high income countries, an area of low-medium income countries with a critical air pollution situation, was selected. The health impact and related external costs attributable to air pollution in 2019 were assessed in 30 urban areas of the Western Balkans region, one of Europe's air pollution hot spots. The evaluation was based on PM2.5, O3 and NO2 concentrations in background sites from official monitoring networks. In 2019, the cost of mortality attributable to PM2.5 in 26 urban areas was 7.8 and 9.0 billion Euro according to IER and CRF methodologies, respectively. The cost of O3 associated with all-cause mortality estimated with the CRF methodology in 17 urban areas was 1.0 billion Euro while the one attributable to NO2 pollution in 28 urban areas was 1.5 billion Euro. The study results suggest that the economic burden of air pollution in the Western Balkans is higher in terms of GDP than the one observed in EU27 in the same time window. The study concludes that CRF and IER methodologies are coherent, because the discrepancy in the results are explained by the differences in the assessed health outcomes. The two approaches are complementary because the combination of them makes it possible to obtain a wider range of outcomes. In addition, despite the different causes of death considered, the comparison between them is useful for cross-validation.


Generation of the iPSC line FINi002-A from a male Parkinson's disease patient carrying compound heterozygous mutations in the PRKN gene.
The most common cause of autosomal recessive familial Parkinson's disease (PD) are mutations in the PRKN/PARK2 gene encoding an E3 ubiquitin protein-ligase PARKIN. We report the generation of an iPSC cell line from the fibroblasts of a male PD patient carrying a common missense variant in exon 7 (p.Arg275Trp), and a 133 kb deletion encompassing exon 8, using transiently-present Sendai virus. The established line displays typical human primed iPSC morphology and expression of pluripotency-associated markers, normal karyotype without SNP array-detectable copy number variations and can give rise to derivatives of all three embryonic germ layers. We envisage the usefulness of this iPSC line, carrying a common and well-studied missense mutation in the RING1 domain of the PARKIN protein, for the elucidation of PARKIN-dependent mechanisms of PD using in vitro and in vivo models.


How should we treat short hepatic veins and paracaval branches in anterior hepatectomy using the hanging maneuver without mobilization of the liver? An anatomical and experimental study.
This study investigates the relevant anatomy for applying the hanging maneuver to hepatectomy by an anterior approach, where liver mobilization is not possible. Using 176 cadaveric livers, we morphometrically investigated the distribution of venous openings within the retrohepatic portion of the inferior vena cava (IVC); next, we conducted a series of experiments to identify which course for insertion of a pair of forceps preserved the thickest of these veins. After anterior dissection of the liver, we carried out an anterior incision along a plane within an area free of venous openings in the IVC. The area free of venous openings was between the thickest caudate vein and the inferior right hepatic vein (IRHV), and averaged 16.2 mm in width. When forceps were inserted along the rightward course connecting the right inferior angle of the right lobe and the same pocket-like space between the terminals of the middle and right hepatic veins, the caudate vein was very likely to be preserved, whereas the IRHV was not. In contrast, the leftward course connecting the gallbladder fossa and the pocket-like space provided an almost opposite incidence of damage. The portal territory of the hilar bifurcation was most likely to be damaged during a virtual incision along an avascular plane; however, the caudate branch of left portal origin was rarely damaged. The rightward course may be the best method for forceps insertion in cases where there is no IRHV. To preserve the caudate vein and the IRHV, taping on the right side of the IRHV and retracting to the right, or changing the direction of the forceps from leftward to rightward when the tip of the forceps is anterior to the IVC is recommended. The hanging maneuver by an anterior approach without mobilization is convenient for right or left hepatectomy for large tumors or hardened liver.


Selective Scalp Nerve Block: A Useful Technique With Tissue Expansion in Postburn Pediatric Alopecia.
Scalp defects can be reconstructed either with skin graft, local flaps, free flaps, or tissue expansion. Tissue expanders have been proved to be fruitful in the pediatric population. Scalp expansion has proved to be useful in the reconstruction of posttraumatic and postburn alopecic defects. Selective nerve block can be added for attenuation of sympathetic stimulation and decrease surgical stress in cranial surgeries. In this study, a comparison was done between using selective nerve block and without selective nerve block in both stages of tissue expansion procedure. This study included 32 different children who underwent tissue expansions in the management of postburn alopecia. Pediatric patients presented with postburn alopecia of the scalp with mature scar were included in this work. Postoperative analgesics were less in children who had received scalp block, whereas it was shorter in patients who did not receive any scalp block. Meperidine consumption was much more less in patients who received selective scalp nerve block. Pain score was markedly decreased in children who had received selective scalp nerve block in the immediate postoperative period. Children who received scalp block showed marked attenuation in the surgical stress responses with minimal changes in heart rate and mean arterial blood pressure after skin incision. Scalp nerve block is considered an excellent choice for postoperative pain control with less need for opioid analgesia.


Development of NLP-Integrated Intelligent Web System for E-Mental Health.
As the COVID-19 pandemic continues, the need for a better health care facility is highlighted more than ever. Besides physical health, mental health conditions have become a significant concern. Unfortunately, there are few opportunities for people to receive mental health care. There are inadequate facilities for seeking mental health support even in big cities, let alone remote areas. This paper presents the structure and implementation procedures for a mental health support system combining technology and professionals. The system is a web platform where mental health seekers can register and use functionalities like NLP-based chatbot for personality assessment, chatting with like-minded people, and one-to-one video conferencing with a mental health professional. The video calling feature of the system has emotion detection capabilities using computer vision. The system also includes downloadable prescription facilities and a payment gateway for secure transactions. From a technological aspect, the conversational NLP-based chatbot and computer vision-powered video calling are the system's most important features. The system has a documentation facility to analyze the mental health condition over time. The web platform is built using React.js for the frontend and Express.js for the backend. MongoDB is used as the database of the platform. The NLP chatbot is built on a three-layered deep neural network model that is programmed in the Python language and uses the NLTK, TensorFlow, and Keras sequential API. Video conference is one of the most important features of the platform. To create the video calling feature, Express.js, Socket.io, and Socket.io-client have been used. The emotion detection feature is implemented on video conferences using computer vision, Haar Cascade, and TensorFlow. All the implemented features are tested and work fine. The targeted users for the platform are teenagers, youth, and the middle-aged population. Mental health-seeking is still considered taboo in some societies today. Apart from basic established facilities, this social dilemma of undergoing treatment for mental health is causing severe damage to individuals. A solution to this problem can be a remote platform for mental health support. With this goal in mind, this system is designed to provide mental health support to people remotely from anywhere worldwide.


[Proteinases of small intestine enterocytes of swine. Purification and properties of aspartyl proteinase similar to cathepsin D].
A new aspartic proteinase was isolated from porcine intestine mucosa by affinity chromatography on pepstatin-Sepharose 4B and gel filtration on Sephadex G-100. The enzyme was purified 1600-fold and appeared homogeneous upon polyacrylamide gel electrophoresis. The proteinase has a Mr 60 000 +/- 4000 Da. During sodium dodecyl sulfate polyacrylamide gel electrophoresis the enzyme produced a single protein band (Mr 30 000 +/- 3000 Da). Isoelectric focusing revealed that the enzyme has several multiple forms (pI 6.9, 7.5, 8,0). The enzyme is a glycoprotein containing 5.9% of carbohydrates; the mannose to galactose ratio is 1:3. The amino acid composition of the enzyme was studied. The proteinase splits an oxidized insulin B-chain and synthetic substrates. The pH optimum is 3.2. The enzyme is immunologically identical to porcine spleen cathepsin D.


Dose intensified molecular targeted radiotherapy for cancer-lymphoma as a paradigm.
Although most patients with locoregional cancer are cured by surgery, radiotherapy, chemotherapy, and combinations thereof, those with distant metastases are not despite systemic chemotherapy. These patients respond to local radiotherapy but generally need systemic therapy. Non-Hodgkin's lymphoma (NHL) provides a paradigm for the role of molecular targeted radiotherapy (MTRT) because these patients have multifocal disease in most cases. Although patients with NHL achieve remissions after multiple cycles of chemotherapy, less than one half of those with aggressive NHL are cured and almost none of those with low grade NHL. Furthermore, NHL, like other cancers, becomes chemoresistant, yet remains responsive to radiotherapy. MTRT, radiation targeted by molecules, is a good strategy for the treatment of multifocal and radiosensitive cancers. Radioimmunotherapy (RIT) is an MTRT approach using MAbs, or parts thereof, to target the radionuclide that delivers radiation. Two anti-CD20 monoclonal antibodies (MAbs), one labeled with (111)In for imaging or (90)Y for therapy and a second labeled with (131)I for imaging and therapy, have proven effective and safe for MTRT for NHL patients. The importance of the radiation is demonstrated in the data from the randomized pivotal trial of (90)Y-ibritumomab; response rates were distinctly better in the (90)Y-ibritumomab arm than in the rituximab arm. Furthermore, the efficacy of (131)I-tositumomab was greater than that of the same MAb alone in another pivotal trial. Although hematologic toxicity is dose limiting for MTRT, febrile neutropenia is uncommon. MTRT is also not associated with mucositis, hair loss, or persistent nausea or vomiting, unlike chemotherapy. Randomized trials of MTRT in different strategies have not been conducted, but there is evidence of better outcomes, particularly for strategies that provide dose intensification, such as pretargeted MTRT, multiple dosing ("fractionation"), and MTRT with stem cell transplantation (SCT). Pretargeted RIT separates delivery of the targeting molecule from radionuclide delivery, provides dose escalation, and is more effective than direct one-step RIT, although more complicated to implement. Improved drugs and strategies for MTRT have documented potential for better patient outcomes. Smaller radionuclide carriers, such as those used for pretargeted MTRT, should be incorporated into the management of patients with NHL and other cancers soon after the patients have proven incurable. Expected improvements using better drugs, strategies, and combinations with other drugs seem likely to make MTRT integral in the management of many patients with cancer and likely to lead to cures of NHL.


Childhood trauma and risky alcohol consumption: a study of Australian adults with low housing stability.
This paper examined whether recall of childhood trauma was associated with adult alcohol consumption in a sample of Australians with low housing security. The secondary aim was to examine whether risky alcohol consumption predicted subsequent housing instability. Sociodemographic factors were examined as potential moderators of these associations. This paper utilised data collected through the Journeys Home Study, a longitudinal study of a representative sample of individuals who were homeless or at risk of homelessness. This paper focused on 1224 participants aged 18 years and over. Data on alcohol use, childhood trauma and sociodemographic characteristics were collected through interviews at baseline. Homeless status at 6- to 12-month follow-up was assessed via interview. Logistic regression modelling was used to examine associations of alcohol consumption with childhood abuse, sociodemographic factors and changes in homelessness status. Self-reported recall of childhood experiences of violence was more likely among current drinkers, risky or not, than among abstainers. Recall of childhood neglect was more common among abstainers than among risky drinkers. The relationships between recall of childhood trauma and adult alcohol consumption are likely to be complex. Risky consumption may contribute to continuing homelessness among adults with unstable housing. [Correction added on 29 December 2014, after first online publication: The Results, and Discussion and Conclusion sections in the abstract have been replaced.].


[Infantile autism among children in the county of Nordland. Prevalence and etiology].
Few epidemiological studies of infantile autism have been conducted in Norway. A prevalence of four per 10,000 children was found in Nord-Trøndelag. Studies from Sweden, England and Japan show prevalence figures of 2-13 per 10,000. Causal factors of autism are complicated, but many studies in recent years indicate that both genetic and neurological factors are important. The aim of this study was to establish the prevalence of infantile autism in Nordland county and look for causal factors and disabilities among the children. Together with the Autism-Team we found 28 persons, born between 1975 and 1991, who lived in the county in 1992. This gives a prevalence of 5.5 per 10,000. 21 were boys, seven girls, 26 were mentally retarded, 13 had no verbal speech. Nine had epilepsy. 13 children were diagnosed before the age of four. Different diseases and impairments associated with autism were discovered in 19 children. In the case of eight children we found associated disease. When a diagnosis of infantile autism is made, the child should undergo a thorough medical and neurological examination. This should include CT brain scan, EEG, chromosome analysis, and screening for metabolic diseases and intrauterine virus infections. Sometimes examinations of liquor and auditory brain-stem responses are indicated.


Anti-inflammatory effect of hepatocyte growth factor in chronic kidney disease: targeting the inflamed vascular endothelium.
Recent studies show that hepatocyte growth factor (HGF) has potent anti-inflammatory effects in multiple animal models of disease in various organ systems, including the kidney, suggesting that HGF may suppress a common proinflammatory process. The aim of this study was to examine the molecular mechanism of HGF's anti-inflammatory actions in a model of chronic kidney disease. Beginning 2 wk after subtotal nephrectomy, rats received a continuous infusion of recombinant HGF, neutralization of endogenous HGF by daily injection of an anti-HGF antibody, or preimmune IgG for an additional 2 wk. The effects on inflammation and injury were examined. HGF administration ameliorated whereas neutralizing endogenous HGF worsened renal inflammation in remnant kidneys. This was accompanied by parallel alterations in endothelial activation and inflammation, marked respectively by de novo E-selectin expression in renal vascular endothelium and leukocyte adhesion to endothelium. In vitro, HGF abrogated monocyte adhesion to TNF-alpha-activated endothelial monolayers and suppressed endothelial expression of E-selectin, which depended on NF-kappaB signaling. In addition, HGF suppressed NF-kappaB reporter gene activity that was induced by TNF-alpha and counteracted TNF-alpha-elicited NF-kappaB interaction with kappaB elements at the E-selectin gene level. Dissection of the NF-kappaB signaling cascade revealed that suppression of NF-kappaB depended on HGF's inhibitory action on NF-kappaB and IkappaB phosphorylation and IkappaB degradation. In vivo, continuous infusion of exogenous HGF markedly diminished sequestration of circulating fluorescence-labeled macrophages in the remnant kidney, mimicking the action of an E-selectin blocking antibody. These findings suggest that HGF has potent and direct anti-inflammatory effects on the basis of suppression of NF-kappaB activation and downstream endothelial inflammation.


Seropositivity and identification of paramyosin for sparganosis in the Kangwon and Incheon provinces of the Republic of Korea.
Sparganosis is one of the top three tissue-dwelling heterologous helminthic diseases, along with cysticercosis and paragonimiasis, in Korea. Due to a lack of effective early diagnosis and treatment methods, this parasitic disease is regarded as a public health threat. This study evaluated reactivity, against sparganum extracts, of sera from inhabitants of Cheorwon-gun, Goseong-gun and Ongjin-gun in Korea. The sera from 836 subjects were subjected to enzyme-linked immunosorbent assay and immunoblot analysis. The sera from 18 (5.8%) and 15 (5.1%) inhabitants in Cheorwon-gun (n = 312) and Goseong-gun (n = 294), respectively, exhibited highly positive reactions to the sparganum antigen, whereas only two (0.9%) inhabitants in Ongjin-gun (n = 230) showed positivity. We sought antigenic proteins for serodiagnosis of positive sera by immunoproteomic approaches. Total sparganum lysates were separated by two-dimensional electrophoresis and then subjected to immunoblot analysis with mixed sparganosis-positive sera. We found seven antigenic spots and identified paramyosin as an antigenic protein by liquid chromatography-mass spectrometry. By two-dimensional (2D)-based mass analysis and immunoblotting against sparganosis-positive sera, paramyosin was identified as a candidate antigen for serodiagnosis of sparganosis.


Direct patterning of intrinsically electron beam sensitive polymer brushes.
The fabrication of patterned polymer brushes has attracted considerable attention as these structures can be exploited in devices on the nano- and microscale. Patterning of polymer brushes is typically a complex, multistep process. We report the direct patterning of poly(methyl methacrylate) (PMMA), poly(2-hydroxyethyl methacrylate) (PHEMA), poly(isobutyl methacrylate) (PIBMA), poly(neopentyl methacrylate) (PNPMA), and poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA) brushes in a single step by electron beam (e-beam) lithography, to obtain nanopatterned polymer brush surfaces. PMMA, PHEMA, PIBMA, PNPMA, and PTFEMA brushes were grown on silicon substrates via surface-initiated atom transfer radical polymerization. Surface analysis techniques including ellipsometry, contact angle goniometry, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS) were used to characterize the thickness, hydrophilicity, roughness, and chemical composition of the polymer brushes. Tapping-mode AFM imaging confirmed the successful electron beam patterning of these brushes. Using this direct patterning method, highly resolved nanostructured polymer brush patterns down to 50 nm lines were obtained. This direct patterning of brushes eliminates the need for complex lithographic schemes. The sensitivity of these polymer brushes toward direct patterning with e-beam was studied and compared. The sensitivity curves indicate that the structure of the e-beam degradable methacrylate polymer has a significant effect on the sensitivity of the polymer brush toward e-beam patterning. In particular, the effect of the chemical functionality at the beta-position to the carbonyl group on the polymer brush sensitivity toward direct patterning was studied using groups of varying size and polarity.


Histochemical and morpho-metrical study of mouse intestine epithelium after a long term diet containing genetically modified soybean.
Diet can influence the structural characteristics of both small and large intestine. In this study, we investigated the duodenum and colon of mice fed on genetically modified (GM) soybean during their whole life span (1-24 months) by focusing our attention on the histological and ultrastructural characteristics of the epithelium, the histochemical pattern of goblet cell mucins, and the growth profile of the coliform population. Our results demonstrate that controls and GM-soybean fed mice are similarly affected by ageing. Moreover, the GM soybean-containing diet does not induce structural alterations in duodenal and colonic epithelium or in coliform population, even after a long term intake. On the other hand, the histochemical approach revealed significant diet-related changes in mucin amounts in the duodenum. In particular, the percentage of villous area occupied by acidic and sulpho-mucin granules decreased from controls to GM-fed animals, whereas neutral mucins did not change.


Neuromuscular and biomechanical factors codetermine the solution to motor redundancy in rhythmic multijoint arm movement.
How the CNS deals with the issue of motor redundancy remains a central question for motor control research. Here we investigate the means by which neuromuscular and biomechanical factors interact to resolve motor redundancy in rhythmic multijoint arm movements. We used a two-df motorized robot arm to manipulate the dynamics of rhythmic flexion-extension (FE) and supination-pronation (SP) movements at the elbow-joint complex. Participants were required to produce rhythmic FE and SP movements, either in isolation, or in combination (at the phase relationship of their choice), while we recorded the activity of key bi-functional muscles. When performed in combination, most participants spontaneously produced an in-phase pattern of coordination in which flexion is synchronised with supination. The activity of the Biceps Brachii (BB), the strongest arm muscle which also has the largest moment arms in both flexion and supination was significantly higher for FE and SP performed in combination than in isolation, suggesting optimal exploitation of the mechanical advantage of this muscle. In a separate condition, participants were required to produce a rhythmic SP movement while a rhythmic FE movement was imposed by the motorized robot. Simulations based upon a musculoskeletal model of the arm demonstrated that in this context, the most efficient use of the force-velocity relationship of BB requires that an anti-phase pattern of coordination (flexion synchronized with pronation) be produced. In practice, the participants maintained the in-phase behavior, and BB activity was higher than for SP performed in isolation. This finding suggests that the neural organisation underlying the exploitation of bifunctional muscle properties, in the natural context, constrains the system to maintain the "natural" coordination pattern in an altered dynamic environment, even at the cost of reduced biomechanical efficiency. We suggest an important role for afference from the imposed movement in promoting the "natural" pattern. Practical implications for the emerging field of robot-assisted therapy and rehabilitation are briefly mentioned.


Taxodione and arenarone inhibit farnesyl diphosphate synthase by binding to the isopentenyl diphosphate site.
We used in silico methods to screen a library of 1,013 compounds for possible binding to the allosteric site in farnesyl diphosphate synthase (FPPS). Two of the 50 predicted hits had activity against either human FPPS (HsFPPS) or Trypanosoma brucei FPPS (TbFPPS), the most active being the quinone methide celastrol (IC50 versus TbFPPS ∼ 20 µM). Two rounds of similarity searching and activity testing then resulted in three leads that were active against HsFPPS with IC50 values in the range of ∼ 1-3 µM (as compared with ∼ 0.5 µM for the bisphosphonate inhibitor, zoledronate). The three leads were the quinone methides taxodone and taxodione and the quinone arenarone, compounds with known antibacterial and/or antitumor activity. We then obtained X-ray crystal structures of HsFPPS with taxodione+zoledronate, arenarone+zoledronate, and taxodione alone. In the zoledronate-containing structures, taxodione and arenarone bound solely to the homoallylic (isopentenyl diphosphate, IPP) site, not to the allosteric site, whereas zoledronate bound via Mg(2+) to the same site as seen in other bisphosphonate-containing structures. In the taxodione-alone structure, one taxodione bound to the same site as seen in the taxodione+zoledronate structure, but the second located to a more surface-exposed site. In differential scanning calorimetry experiments, taxodione and arenarone broadened the native-to-unfolded thermal transition (Tm), quite different to the large increases in ΔTm seen with biphosphonate inhibitors. The results identify new classes of FPPS inhibitors, diterpenoids and sesquiterpenoids, that bind to the IPP site and may be of interest as anticancer and antiinfective drug leads.


Improvement of ultrafast holographic performance in silver nanoprisms dispersed photopolymer.
This work demonstrates the grating formation of bulk nanoparticle polymer composites through an improved interference optical system under ultrafast nanoseconds exposure of a silver nanoprisms (NPs) dispersed photo-polymerizable mixture in the case of 532 nm wavelength. The polymerizable mixture is composed of phenathrenequinone (PQ) (photoinitiator) and methyl methacrylate (MMA) (monomer). The mechanism in this bulk nanoparticle polymer composite is analyzed by mixing nonlocal polymerization driven diffusion (NPDD) model and absorption modulation caused by the spatial concentration distribution difference of silver NPs. We find that the attenuation of diffraction efficiency under pulsed exposure is due to the reciprocity law failure. This work presents an analysis of the cause of reciprocity failure and improvement in holographic properties by doping silver NPs. The optimized photopolymer presents diffraction efficiencies as high as 51.4% with 1.8 μs cumulative pulsed exposure. Cumulative gratings strength is also enhanced by 70% while doping silver NPs under 1.5 μs cumulative pulsed exposure.


Xanthine oxidase inactivation by reagents that modify thiol groups.
1. The presence of xanthine was required for the inhibition of bovine milk xanthine oxidase by o-iodosobenzoate, iodoacetamide, hydrogen peroxide or p-chloromercuribenzoate. 2. Inactivation by p-chloromercuribenzoate was very rapid, was reversed by cysteine and was less in the presence of FAD. Lineweaver-Burk plots showed that the inactivation by p-chloromercuribenzoate was competitive with substrate. 3. Inactivation by o-iodosobenzoate, iodoacetamide or hydrogen peroxide could not be reversed by cysteine or xanthine. However, the presence of xanthine during the incubation with inhibitor protected the enzyme against o-iodosobenzoate but not against iodoacetamide or hydrogen peroxide. 4. p-Chloromercuribenzoate protected the enzyme against inactivation by hydrogen peroxide.


Reliability and Measurement Error of the Qualitative Analysis of Single Leg Loading (QASLS) Tool For Unilateral Tasks.
Movement quality assessment is popular within clinical and sporting practice, due to the contribution diminished or suboptimal movement quality is believed to have on musculoskeletal (MSK) injury risk. Various movement quality assessments exist, many are limited to bilateral or jumping movements evaluation. Qualitative analysis of single leg loading (QASLS) is a new clinical assessment tool for unilateral tasks that utilizes a dichotomous scoring system of ten questions relating to the segmental body regions of the trunk, lower and upper limb. To determine the intra and inter-rater, within- and between-session reliability of the QASLS tool during two unilateral movement tasks, and provide insight to measurement error and smallest detectable difference (SDD). Reliability Study. Fifteen healthy females (mean age 19 years SD2; height 167 cm, +/- 6; weight 56 kg, +/- 6) completed two unilateral tasks, single leg squat (SLS) and single leg landing (SLL), within session data collection occurred on the same day, with between session data collection occurring seven days later. Tasks were scored with the QASLS tool via video playback. Intra-Class correlation coefficients (ICCk,3) were used to measure within and between session reliability, and Kappa coefficients and percentage of exact agreement (PEA%) were used to determine intra and inter-rater reliability. Standard error of measurement (SEM) and the SDD for the compound score of each limb was calculated. Within session reliability of QASLS scores was good (ICC = 0.82-0.86) for SLS and moderate (ICC = 0.67-0.87) for SLL. Between session reliability was moderate (ICC = 0.69-0.87) for SLS and excellent (ICC = 0.92-0.93) for SLL. SEM was less than 1 point, and SDD for compound score ranging from 1.0-2.5 points. Intra-rater agreement of compound QASLS score was near perfect (k = 0.85-100; PEA% 90-100%) and agreement of individual components was substantial- near perfect (k = 0.13-0.74; PEA% 78-100%). Inter-rater agreement for compound QASLS scores ranged from non-substantial (k = 0.13-0.74; PEA% 43.3-90%) for SLS and non-slight (k =0.03-0.17; PEA% 43.3-60%) for SLL. The QASLS movement analysis tool can be used to analyze movement quality during two unilateral loading tasks with moderate to excellent within and between session reliability. PEA% was acceptable for inter-rater agreement, however rater education training is recommended to develop more acceptable levels of reliability. 3.


Diabetes and the socioeconomic and built environment: geovisualization of disease prevalence and potential contextual associations using ring maps.
Efforts to stem the diabetes epidemic in the United States and other countries must take into account a complex array of individual, social, economic, and built environmental factors. Increasingly, scientists use information visualization tools to "make sense" of large multivariate data sets. Recently, ring map visualization has been explored as a means of depicting spatially referenced, multivariate data in a single information graphic. A ring map shows multiple attribute data sets as separate rings of information surrounding a base map of a particular geographic region of interest. In this study, ring maps were used to evaluate diabetes prevalence among adult South Carolina Medicaid recipients. In particular, county-level ring maps were used to evaluate disparities in diabetes prevalence among adult African Americans and Whites and to explore potential county-level associations between diabetes prevalence among adult African Americans and five measures of the socioeconomic and built environment--persistent poverty, unemployment, rurality, number of fast food restaurants per capita, and number of convenience stores per capita. Although Medicaid pays for the health care of approximately 15 percent of all diabetics, few studies have examined diabetes in adult Medicaid recipients at the county level. The present study thus addresses a critical information gap, while illustrating the utility of ring maps in multivariate investigations of population health and environmental context. Ring maps showed substantial racial disparity in diabetes prevalence among adult Medicaid recipients and suggested an association between adult African American diabetes prevalence and rurality. Rurality was significantly positively associated with diabetes prevalence among adult African American Medicaid recipients in a multivariate statistical model. Efforts to reduce diabetes among adult African American Medicaid recipients must extend to rural African Americans. Ring maps can be used to integrate diverse data sets, explore attribute associations, and achieve insights critical to the promotion of population health.


[Hepatic metabolism of cholesterol].
Cholesterol is an essential component of all tissues, as it is a part of the structure of cell membranes, and it is an immediate precursor of a series of essential substances such as vitamins, steroid hormones, and bile acids. Under physiologic conditions, the intake and output of cholesterol in the organism is coordinated and balanced with the aim of guaranteeing the availability of adequate amounts of cholesterol to satisfy the needs of the different tissues (fig. 1). Under pathological conditions there is an imbalance between these mechanism, which leads to an increase in the circulating levels of cholesterol, leading to pathological processes such as hyperlipemias, atherosclerosis and bile stones. The liver plays a central role in the regulation of the homeostasis of cholesterol. The molecule enters the liver in the form of chylomicrons and low density lipoproteins (LDL), through lipoprotein receptors, and this is also the most important organ for the de novo biosynthesis of cholesterol from acetyl coenzyme A, by means of a cascade enzyme reaction in which the enzyme 3-hydroxy-3 methyl glutaryl CoA reductase (HMG-CoA) is the key of the entire process. Cholesterol is found in the liver in the form of cholesterol esters or as free cholesterol. The two most effective ways of eliminating body cholesterol are found in the liver, with the degradation of the compound to bile acids and the biliary secretion of cholesterol. The conversion to bile acids takes place through a series of enzymatic steps in which the formation of 7-alpha-hydroxycholesterol by the enzyme cholesterol 7-alpha-hydroxylase is the key of the process. The biliary secretion of cholesterol is 600 mg/day. Both the abundance and the universality of cholesterol in living things as its clinical implications emphasize the importance and interest of this compound.


Seizure and hemiparesis at high-altitude outside the setting of acute mountain sickness.
Neurologic problems at high altitudes are well known. What is probably less emphasized are neurologic problems at altitude outside the setting of high-altitude cerebral edema. Because neurologic symptoms for these kinds of problems at high altitude are often transient, neuroradiologic scanning for these problems is usually not done or reported. Furthermore, diagnostic testing facilities may be unavailable in these remote high-altitude settings. A patient is described here with transient seizure and right-sided hemiparesis at high altitude with no preceding symptoms of acute mountain sickness. Computed tomography of the head was obtained in a hospital at lower altitude where the patient was taken promptly. The findings of the scan revealed probable focal cerebral edema in the left parietal lobe in keeping with his temporary right-sided weakness. Possible treatment modalities on the mountain for this problem are also discussed.


Efficient adenoviral vector-directed expression of a foreign gene to neurons and sustentacular cells in the mouse olfactory neuroepithelium.
Replication deficient recombinant adenoviral vectors are efficient gene transfer agents for postmitotic cells, including neurons and glial cells. In this paper we have examined the effectiveness of adenoviral vector-mediated gene transfer to the olfactory epithelium of adult mice. We show that Ad-LacZ, a prototype first generation adenoviral vector containing an expression cassette for the reporter gene LacZ, directs transgene expression to mature and immature olfactory neurons and to sustentacular cells. The technique to apply the vector to the nasal cavity and the amount of viral vector per mouse are important variables that determine the success of viral vector-mediated gene transfer to the mouse olfactory neuroepithelium. Slow infusion of the viral vector solution in fully anaesthetized mice yields the best result in terms of the number of epithelial cells transduced. Infection of the olfactory neuroepithelium with a moderate amount of viral vector (10(9) plaque-forming units (PFU)) results in transgene expression in many cells throughout the epithelium for 8-12 days, followed by a decline in transduced cells at 25 days postinstillation of the virus This decrement in transgene expression is consistent with the natural turnover process that occurs in the epithelium throughout adulthood. At high viral loads (1.3 x 10(10) PFU) extinction of transgene expression occurs as early as 8 days postinjection and is accompanied by epithelial degeneration indicating that the vector dose used should be carefully chosen. Taken together, the current observations demonstrate that adenoviral vectors are effective tools to genetically modify the adult mouse olfactory neuroepithelium in vivo.