Stress-related alcohol consumption in heavy drinkers correlates with expression of miR-10a, miR-21, and components of the TAR-RNA-binding protein-associated complex.
Alterations in stress-related gene expression may play a role in stress-related drinking and the risk of alcohol dependence. Microarrays were used to measure changes in gene expression in peripheral blood in nonsmoking, social drinking subjects exposed to 3 types of personalized imagery: neutral, stressful (but not alcohol related), and alcohol-related cues. Gene expression was measured at baseline, immediately after, and 1 hour after stimulus presentation. Subjects were allowed to drink up to 750 cc of beer in a "taste test" following stimulus presentation in each imagery condition, and the amount of beer consumed was recorded. Gene-expression levels were compared in 2 groups of nonsmoking subjects (n = 11/group): heavy drinkers (HD; defined as regular alcohol use over the past year of at least 8 standard drinks per week for women and at least 15 standard drinks per week for men), and moderate drinkers (MD; defined as up to 7 standard drinks per week for women and 14 standard drinks per week for men). Expression of microRNA-10a (miR-10a) and microRNA-21 (miR-21) was assessed by quantitative real-time polymerase chain reaction. After correction for multiple testing (false discovery rate < 0.05), 79 genes were identified that changed by >1.3-fold in the HD group, but not the MD group, following exposure to stress. No changes were observed for any of these genes in either group following exposure to neutral or alcohol-related imagery. Pathway analysis suggested that many of these genes, form part of the transactivation responsive (TAR)-RNA-binding protein (TRBP)-associated complex and are positively regulated by miR-10a and miR-21. Expression of both miR-10a and miR-21 was up-regulated following psychological stress in HD, but not MD subjects; however, the differences between groups were not statistically significant. Expression levels of both microRNAs was correlated (miR-10a, R(2) = 0.59, miR-21 R(2) = 0.57) with amount drunk in HD, but not MD subjects. Expression of miR-10a, miR-21, and several of their target genes is regulated by acute psychological stress and is correlated with stress-induced drinking in a laboratory setting. Alterations in miRNA expression may be one mechanism linking psychological stress with changes in gene expression and increased alcohol intake in binge/HD.


Patterns of visits to physicians' offices, 1980 to 2003.
In the past quarter century, the number of office visits to physicians in the United States increased from 581 million per year to 838 million per year, with slightly more than one half of total visits since 1980 being made to primary care physicians. Most visits to primary care physicians were made to family physicians (FPs) and general practitioners (GPs) until the mid 1990s, when visits to general internists and general pediatricians exceeded visits to FPs and GPs.


Species synchrony and its drivers: neutral and nonneutral community dynamics in fluctuating environments.
Independent species fluctuations are commonly used as a null hypothesis to test the role of competition and niche differences between species in community stability. This hypothesis, however, is unrealistic because it ignores the forces that contribute to synchronization of population dynamics. Here we present a mechanistic neutral model that describes the dynamics of a community of equivalent species under the joint influence of density dependence, environmental forcing, and demographic stochasticity. We also introduce a new standardized measure of species synchrony in multispecies communities. We show that the per capita population growth rates of equivalent species are strongly synchronized, especially when endogenous population dynamics are cyclic or chaotic, while their long-term fluctuations in population sizes are desynchronized by ecological drift. We then generalize our model to nonneutral dynamics by incorporating temporal and nontemporal forms of niche differentiation. Niche differentiation consistently decreases the synchrony of species per capita population growth rates, while its effects on the synchrony of population sizes are more complex. Comparing the observed synchrony of species per capita population growth rates with that predicted by the neutral model potentially provides a simple test of deterministic asynchrony in a community.


Competition between suppression and production of Fermi acceleration.
The behavior of the average velocity for a classical particle in the one-dimensional Fermi accelerator model under sawtooth external force is considered. For elastic collisions, it is known that the average velocity of the particle grows unlimitedly because of the discontinuities of the derivative of the moving wall's position with respect to time. However, and contrary to what was expected to be observed, the introduction of a friction force generated from a slip of a body against a rough surface leads to a boundary separating different regions of the phase space that yields the particle to either experience unlimited energy growth or suppression of Fermi acceleration. The Fermi acceleration is described by using scaling arguments. The formalism presented can be extended to two-dimensional time-dependent billiards as well as to higher-order mappings.


PEO-PPO Diblock Copolymers Protect Myoblasts from Hypo-Osmotic Stress In Vitro Dependent on Copolymer Size, Composition, and Architecture.
Poloxamer 188, a triblock copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), protects cellular membranes from various stresses. Though numerous block copolymer variants exist, evaluation of alternative architecture, composition, and size has been minimal. Herein, cultured murine myoblasts are exposed to the stresses of hypotonic shock and isotonic recovery, and membrane integrity was evaluated by quantifying release of lactate dehydrogenase. Comparative evaluation of a systematic set of PEO-PPO diblock and PEO-PPO-PEO triblock copolymers demonstrates that the diblock architecture can be protective in vitro. Short PPO blocks hinder protection with >9 PPO units needed for protection at 150 μM and >16 units needed at 14 μM. Addition of a tert-butyl end group enhances protection at reduced concentration. When the end group and PPO length are fixed, increasing the PEO length improves protection. This systematic evaluation establishes a new in vitro screening tool for evaluating membrane-sealing amphiphiles and provides mechanistic insight to guide future copolymer design for membrane stabilization in vivo.


Tuberculous retinal vasculitis.
A case of central retinal vasculitis associated with culture proven active pulmonary tuberculosis is presented. The ocular condition responded dramatically to systemic isoniazid and ethambutol. The clinical picture of central retinal vein occlusion should alert the physician to the possibility of an inflammatory etiology. Appropriate studies to rule out treatable inflammatory conditions should be ordered.


[Antitumor Chemical Entities of Cordyceps taii Mycelia Powder from Guizhou].
To seperate and identify the chemicals from the antitumor fraction of Cordyceps taii mycelia powder. The mycelia of Cordyceps taii were prepared by the submerged fermentation technique. Chemical entities in the antitumor fraction of Cordyceps taii were isolated and purified by using different column chromatographies (silica gel, Sephadex LH-20 and MCI), and semi-preparative HPLC method. Theirs chemical structures were then identified by different spectrum techniques such as EI, ESI and 1D/2D-NMR, etc. The cytotoxic activity was investigated by the Sulforhodamine B (SRB) assay. Six compounds, such as 5α,8α-epidioxyergosta-6,22-dien-3β-ol (1), ergosterol (2), adenine nucleoside (3), helvolic acid (4), deacetylcytochalasin C (5) and zygosporin D (6), were identified. The IC50 value of compound 2 against human gastric cancer cell line SGC-7901 was 5.99 μmol/L, which was less than the half value of cisplatin, and had lower cytotoxicity to normal cells in comparison with cisplatin. Six compounds have been isolated from the antitumor fraction of Cordyceps taii mycelia powder,of which compounds 1, 5 and 6 are isolated from Cordyceps taii for the first time. Compounds 1, 2 and 4 have cytotoxic activities against cancer cells, and should be the main antitumor compounds of Cordyceps taii.


Utilization Trends of Nerve Autograft Alternatives for the Reconstruction of Peripheral Nerve Defects.
Autologous nerve grafting is the time-honored reconstruction method for peripheral nerve gaps. However, it is associated with donor site morbidities. A growing number of studies have demonstrated the effective use of decellularized nerve allograft and synthetic conduits, which are convenient options with no donor deficit. The specific aim of this study was to characterize changes in practice trends for peripheral nerve defect reconstruction. We queried the 2015-2020 Truven MarketScan database for patients who underwent nerve autograft, allograft, synthetic conduit, and/or vein graft reconstruction. Patient demographic data (i.e. location, indication) and hospital characteristics (i.e. facility, provider type) were recorded. Regression analysis identified changes in trends over the study period. 4331 patients underwent one or more nerve gap reconstructive procedures over the study period. Since the introduction of allograft CPT code in 2018, segmented mixed effect longitudinal modeling revealed allograft utilization significantly increased from 21.5% to 29.6% after 2018 (p<0.001), whereas nerve autograft utilization decreased from 18.6% to 15.8% and conduit utilization decreased from 60% to 54.7% (p=0.09 and p=0.03, respectively). When stratifying autograft by size, use of autograft ≥4cm significantly decreased from 10.6% to 7.7% after 2018 (p=0.03), and autograft >4cm did not. When stratifying by state, there is heterogeneity in utilizati. After creation of a designated allograft CPT code in 2018, there was an increase in allograft use with concomitant decrease in conduit and short length autograft use, suggesting that allograft replaced a portion of procedures used in short nerve gap reconstruction.


Evaluating the accuracy of a density functional theory of polymer solutions with additive hard sphere diameters.
We assess the accuracy of a density functional theory for athermal polymer solutions, consisting of solvent particles with a smaller radius than that of the monomers. The monomer and solvent density profiles in a slit bound by hard, flat, and inert surfaces are compared with those obtained by a Metropolis Monte Carlo simulation. At the relatively high density at which the comparison is performed, there are considerable packing effects at the walls. The density functional theory introduces a simple weight function to describe nonlocal correlations in the fluid. A recent study of surface forces in polymer solutions used a different weighting scheme to that proposed in this article, leading to less accurate results. The implications of the conclusions of that study are discussed.


Myocardial stress after competitive exercise in professional road cyclists.
Based on the determination of cardiac troponin (cTnT), brain natriuretic peptide (BNP), and echocardiographic measurements, recent investigations have reported myocardial damage and reversible cardiac dysfunction after prolonged endurance exercise in apparently healthy subjects. In the present study, we investigated the myocardial stress reaction in professional endurance athletes after strenuous competitive physical exercise. Eleven highly trained male professional road cyclists (age 27 +/- 4 yr; .VO2peak 67 +/- 5 mL.kg-1.min-1; training workload 34,000 +/- 2,500 km.yr-1) were examined. The following parameters were determined before and after one stage of a 5-d professional cycling race: BNP, cTnT (third-generation assay that shows no cross reactivity with skeletal TnT), creatine kinase (CK), creatine kinase MB (CKMB), myoglobin (Myo), and urea. All participants were submitted to a careful cardiac examination including echocardiography and stress ECG. None of the athletes showed pathological findings in the cardiac examination. CK (P < 0.01), CKMB (P < 0.05), and Myo (P < 0.01) were increased after the race. Normal postexercise cTnT levels indicate that the increase in CK, CKMB, and Myo was of noncardiac origin. In contrast, BNP rose significantly from 47.5 +/- 37.5 to 75.3 +/- 55.3 pg.mL-1 (P < 0.01). Pre- and postexercise values of BNP as well as the individual exercise-induced increase in BNP were significantly correlated with age (R2 = 0.68, R2 = 0.66, and R2 = 0.58, respectively; P < 0.05). Strenuous endurance exercise in professional road cyclists does not result in structural myocardial damage. The rise in BNP in older athletes may reflect a reversible, mainly diastolic left ventricular dysfunction. This needs to be confirmed by larger trials including different intensities, sports, and age groups.


New species of Dictyochaetopsis and Paraceratocladium from Brazil.
Two new conidial fungi, Dictyochaetopsis brasiliensis and Paraceratocladium bacilliformis, both isolated from plant debris collected in Brazil, are described and illustrated. Dictyochaetopsis brasiliensis differs from the previously described species of the genus mainly by small, fusiform conidia with a very thin apical setula, absence of setae, and lateral, discrete conidiogenous cells with usually numerous sympodial proliferations. Paraceratocladium bacilliformis is characterized by small, bacilliform and aseptate conidia.


Getting to the Heart of the Story: Using Talanoa to Explore Pacific Mental Health.
Talanoa is an established format for generating discussion about complex topics used throughout the Pacific. Pacific researchers use talanoa to gather data with migrant Pacific Island populations, in countries such as the United States of America, Australia, and Aotearoa/New Zealand (A/NZ). Using talanoa in this way, changes the way that the approach is used as, on the one hand it is out of its original context, and on the other hand, extends its use to gather data with Pacific Islanders. In this article, we discuss the implementation of talanoa in an explorative qualitative research project, and discuss its effectiveness and usefulness for getting to the heart of the story about Tongan interpretations of mental illness and distress.


Molecular cloning and expression of Chinese hamster ovary cell heparan-sulfate 2-sulfotransferase.
Heparan-sulfate 2-sulfotransferase (HS2ST), which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to L-iduronic acid at position 2 in heparan sulfate, was purified from cultured Chinese hamster ovary (CHO) cells to apparent homogeneity (Kobayashi, M., Habuchi, H., Habuchi, O., Saito, M., and Kimata, K. (1996) J. Biol. Chem. 271, 7645-7653). The internal amino acid sequences were obtained from the peptides after digestion of the purified protein with a combination of endoproteinases. Mixed oligonucleotides based on the peptide sequences were used as primers to obtain a probe fragment by reverse transcriptase-polymerase chain reaction using CHO cell poly(A)+ RNA as template. The clone obtained from a CHO cDNA library by screening with the probe is 2.2 kilobases in size and contains an open reading frame of 1068 bases encoding a new protein composed of 356 amino acid residues. The protein predicts a type II transmembrane topology similar to other Golgi membrane proteins. Messages of 5.0 and 3.0 kilobases were observed in Northern analysis. Evidence that the cDNA clone corresponds to the purified HS2ST protein is as follows. (a) The predicted amino acid sequence contains all five peptides obtained after endoproteinase digestion of the purified protein; (b) the characteristics of the predicted protein fit those of the purified protein in terms of molecular mass, membrane localization, and N-glycosylation; and (c) when the cDNA containing the entire coding sequence of the enzyme in a eukaryotic expression vector was transfected into COS-7 cells, the HS2ST activity increased 2.6-fold over controls, and the FLAG-HS2ST fusion protein purified by affinity chromatography showed the HS2ST activity alone.


Erratum: Novel Genetic Associations Between Lung Cancer and Indoor Radon Exposure.
[This corrects the article on p. 234 in vol. 22, PMID: 29302581.].


Topiramate treatment in bulimia nervosa patients: a randomized, double-blind, placebo-controlled trial.
The aim of the current study was to test the influence of topiramate on behavior, body weight, and health-related quality of life (HRQOL) in bulimic patients. Thirty patients with bulimia nervosa were treated with topiramate in a 10-week randomized, double-blind, placebo-controlled study. The subjects were randomly assigned to receive topiramate (topiramate group [TG]; n = 30) or a placebo (control group [CG]; n = 30). Primary outcome measures were changes in the frequency of binging/purging, in body weight, and on the SF-36 Health Survey (SF-36) scales. In comparison to the CG group (according to the intent-to-treat principle), significant changes in the frequency of binging/purging (a > 50% reduction: TG, n = 11 [36.7%]; CG, n = 1 [3.3%]; p < .001), body weight (difference in weight loss between the two groups: 3.8 kg, 95% confidence interval [CI] = -5.4 to -2.1; p < .001), and SF-36 (all ps < .001) could be seen. All patients tolerated topiramate well. Topiramate appears to safe and effective in influencing the frequency of binging/purging, body weight, and HRQOL in bulimic patients.


Relationship of self-concept during late pregnancy to neonatal perception and parenting profile.
Thirty-one gravidas were studied to examine the relationship between a woman's feelings about herself during late pregnancy, her perception of her newborn, and her profile of parenting. The Tennessee Self-Concept Scale was completed during the third trimester of pregnancy, the Neonatal Perception Inventory I at one-to-two days postpartum, and the Neonatal Perception Inventory II and the Michigan Screening Profile of Parenting at four-to-six weeks postpartum. When considered separately, no positive significant relationships were found between scores on these variables. However, all subjects with negative scores on both self-concept and neonatal perception had negative scores on at least two subscales of the parenting profile.


Exploiting the PIR Sensor Analog Behavior as Thermoreceptor: Movement Direction Classification Based on Spiking Neurons.
Pyroelectric infrared sensors (PIR) are widely used as infrared (IR) detectors due to their basic implementation, low cost, low power, and performance. Combined with a Fresnel lens, they can be used as a binary detector in applications of presence and motion control. Furthermore, due to their features, they can be used in autonomous intelligent devices or included in robotics applications or sensor networks. In this work, two neural processing architectures are presented: (1) an analog processing approach to achieve the behavior of a presynaptic neuron from a PIR sensor. An analog circuit similar to the leaky integrate and fire model is implemented to be able to generate spiking rates proportional to the IR stimuli received at a PIR sensor. (2) An embedded postsynaptic neuron where a spiking neural network matrix together with an algorithm based on digital processing techniques is introduced. This structure allows connecting a set of sensors to the post-synaptic circuit emulating an optic nerve. As a case study, the entire neural processing approach presented in this paper is applied to optical flow detection considering a four-PIR array as input. The results validate both the spiking approach for an analog sensor presented and the ability to retrieve the analog information sent as spike trains in a simulated optic nerve.


Consistency of covid-19 trial preprints with published reports and impact for decision making: retrospective review.
To assess the trustworthiness (ie, complete and consistent reporting of key methods and results between preprint and published trial reports) and impact (ie, effects of preprints on meta-analytic estimates and the certainty of evidence) of preprint trial reports during the covid-19 pandemic. Retrospective review. World Health Organization covid-19 database and the Living Overview of the Evidence (L-OVE) covid-19 platform by the Epistemonikos Foundation (up to 3 August 2021). Comparison of characteristics of covid-19 trials with and without preprints, estimates of time to publication of covid-19 preprints, and description of differences in reporting of key methods and results between preprints and their later publications. For the effects of eight treatments on mortality and mechanical ventilation, the study comprised meta-analyses including preprints and excluding preprints at one, three, and six months after the first trial addressing the treatment became available either as a preprint or publication (120 meta-analyses in total, 60 of which included preprints and 60 of which excluded preprints) and assessed the certainty of evidence using the GRADE framework. Of 356 trials included in the study, 101 were only available as preprints, 181 as journal publications, and 74 as preprints first and subsequently published in journals. The median time to publication of preprints was about six months. Key methods and results showed few important differences between trial preprints and their subsequent published reports. Apart from two (3.3%) of 60 comparisons, point estimates were consistent between meta-analyses including preprints versus those excluding preprints as to whether they indicated benefit, no appreciable effect, or harm. For nine (15%) of 60 comparisons, the rating of the certainty of evidence was different when preprints were included versus being excluded-the certainty of evidence including preprints was higher in four comparisons and lower in five comparisons. No compelling evidence indicates that preprints provide results that are inconsistent with published papers. Preprints remain the only source of findings of many trials for several months-an unsuitable length of time in a health emergency that is not conducive to treating patients with timely evidence. The inclusion of preprints could affect the results of meta-analyses and the certainty of evidence. Evidence users should be encouraged to consider data from preprints.


How important is stimulation of alpha-adrenoceptors for melatonin production in rat pineal glands?
The objective of this study was to determine the role of alpha-adrenoceptors in melatonin production by rat pineal gland. Pineal glands were isolated from adult male rats and maintained in organ baths. The perfusate was sampled every 5 min, stored, and later assayed for melatonin. Exposure to norepinephrine (10 microM) or the beta-adrenoceptor agonist orciprenaline (2-10 microM) increased the glands' production of melatonin. The time courses of melatonin production in response to these agonists were unaffected by the rats' pretreatment in vivo with the alpha-adrenoceptor antagonist prazosin (2 mg/kg i.p., three times). Rats that had had their superior cervical ganglia removed were primed with either orciprenaline (2 mg/kg i.p) or both orciprenaline and phenylephrine (1 mg/kg i.p) 1 hr before decapitation. Exposure of the pineal glands from these rats to orciprenaline evoked melatonin release that was similar in each group. These results lend weight to the suggestion that the marked potentiation by alpha-adrenoceptor agonists of the stimulation of cAMP and N-acetyltransferase (NAT) by beta-adrenoceptor agonists, demonstrated most readily in cultured glands or dispersed rat pinealocytes, does not carry over into significant augmentation of melatonin production in intact pineal glands.


Isolated lateral ventricular asymmetry in very low-birth-weight infants: a left-sided lesion?
We prospectively performed serial cranial ultrasonography to determine the incidence of asymmetry of the lateral ventricles in very low-birth-weight (VLBW) infants (500-1500 g) who did not have evidence of other intracranial pathology. Of the 490 babies scanned, 354 were free of other pathology and 41 (11.6%) had isolated ventricular asymmetry. In 10 infants, the asymmetry was seen on the initial scan and in 31, it developed subsequently. In 19 infants, the ventricular asymmetry resolved and in 22 infants it persisted until hospital discharge. In no case was progressive enlargement of the ventricles noted. There was a striking tendency of the larger ventricle to be on the left side (33 L>R, 8 R>L). Compared with a control group of babies matched for birth weight and gestational age who had persistently negative scans, there were no differences in Apgar scores, cesarean section rate, gender distribution, prenatal steroid exposure, or complications of prematurity except for an increased incidence of respiratory distress syndrome requiring surfactant in the group with ventricular asymmetry (63% vs. 29%, p = 0.04). Ventricular asymmetry is common in VLBW infants, but whether it is an incidental finding or represents subtle brain injury is unknown.


The glycopatterns of Pseudomonas aeruginosa as a potential biomarker for its carbapenem resistance.
Multidrug-resistant (MDR) Pseudomonas aeruginosa infections pose a significant challenge to effective treatment. Although carbapenems were once considered the primary therapeutic option for MDR P. aeruginosa, the clinical use of these antibiotics has become increasingly limited, and the exploration of alternative antimicrobial strategies remains necessary. Bacterial surface glycans are critical in response to antibiotics and represent an attractive therapeutic target. However, the understanding of the role of glycan structures in bacterial resistance is currently quite limited. In this study, we used lectin microarrays to analyze the differences in glycan alterations between 53 drug-sensitive P. aeruginosa (DSPA) strains and 57 carbapenem-resistant P. aeruginosa (CRPA) strains obtained from clinical isolates, with the goal of identifying important glycopatterns associated with carbapenem resistance. The results revealed significant differences in the expression levels of glycan structures [e.g., Fucα1-6GlcNAc, α-d-Man, and Fucα1-3(Galβ1-4)GlcNAc] recognized by 20 lectins (e.g., LCA, PSA, and AAL) on the bacterial surface. Furthermore, we applied K-fold cross-validation to determine the optimal parameters and constructed the DSPA and CRPA models using gradient boosting decision tree (GBDT) algorithm. The GBDT model presented the best performance in an independent test cohort, demonstrating that the screened glycopatterns could serve as potential biomarkers for differentiating bacterial resistance. Our study is the first to apply lectin microarrays to monitor carbapenem resistance in clinical P. aeruginosa isolates, and we hope that the methodology used in this work will serve as an important tool for exploring the association of bacterial resistance with glycosylation mechanisms.IMPORTANCEBacterial surface glycans are an attractive therapeutic target in response to antibiotics; however, current knowledge of the corresponding mechanisms is rather limited. Antimicrobial susceptibility testing, genome sequencing, and MALDI-TOF MS, commonly used in recent years to analyze bacterial resistance, are unable to rapidly and efficiently establish associations between glycans and resistance. The discovery of new antimicrobial strategies still requires the introduction of promising analytical methods. In this study, we applied lectin microarray technology and a machine-learning model to screen for important glycan structures associated with carbapenem-resistant P. aeruginosa. This work highlights that specific glycopatterns can be important biomarkers associated with bacterial antibiotic resistance, which promises to provide a rapid entry point for exploring new resistance mechanisms in pathogens.


Identifying the learning curve for total ankle replacement using a mobile bearing prosthesis.
Total ankle arthroplasty remains a technically demanding surgery highly influenced by the operator experience. However, no consensus exists regarding the ideal number of cases that need to be performed before a surgeon is considered proficient. The aim of this study was to identify the learning curve of a specific replacement system with regards to intraoperative and postoperative outcomes. The first 31 patients undergoing total ankle arthroplasty were examined. No additional procedures were performed at the time of the TAA. Intraoperative characteristics, postoperative complications, as well as clinical and radiologic outcomes were assessed with 24-month follow-up. Learning curves, examining the relationship between surgeon experience and patient outcomes, were determined using the Moving Average Method. The operatory time, and the risk of intraoperative fractures decreased with increasing surgeon experience with the learning curve stabilizing after the 14th and 24th patient, respectively. Furthermore, there appeared to be a learning curve associated with most of the important clinical and radiological outcomes. The number of patients required to stabilize the learning curve for the VAS, ROM, and AOFAS was 11, 14 and 28, respectively. Radiographically, there appeared to be a learning curve of 22 patients required to stabilize the tibio-talar ratio. There was no learning curve associated with the SF-12 PCS and MCS as well as the α-, β-, and γ-angle. This study demonstrates that a surgical learning curve does indeed exist when performing TAA. Most of the operative variables as well as clinical and radiological outcomes stabilize after a surgeon has performed 28 cases.


Immunomodulatory Activity of Octenyl Succinic Anhydride Modified Porang (Amorphophallus oncophyllus) Glucomannan on Mouse Macrophage-Like J774.1 Cells and Mouse Primary Peritoneal Macrophages.
Porang is a local plant of Indonesia, which has a high content of glucomannan. In this study, porang glucomannan (PG) was esterified with octenyl succinic anhydride (OSA) to enhance emulsion properties to be widely used in food industry. OSA-modified PG (OSA-PG) enhanced the phagocytosis activity of macrophage-like J774.1 cells and mouse peritoneal macrophages. In addition, OSA-PG increased the production of IL-6 and TNF-α by enhancing their gene expression. Immunoblot analysis displayed that OSA-PG tended to activate both nuclear factor-κB and mitogen-activated protein kinase cascades. Treatment of OSA-PG with polymyxin B revealed that cytokine production induced by OSA-PG was not caused by endotoxin contamination. Our findings also indicated that OSA-PG activates macrophages through not only Toll-like receptor (TLR) 4, but another receptor. Overall findings suggested that OSA-PG has a potential as an immunomodulatory food factor by stimulating macrophages.


Weight and survival after deep brain stimulation for Parkinson's disease.
Weight loss in Parkinson's disease (PD) is common and associated with increased mortality. The clinical significance of weight changes following deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) is unclear. To address (1) whether PD patients exhibit progressive weight loss, (2) whether staged DBS surgery is associated with weight changes, and (3) whether survival after DBS correlates with post-DBS weight. This is a single-center, longitudinal, retrospective cohort study of 1625 PD patients. We examined trends in weight over time and the relationship between weight and years survival after DBS using regression and mixed model analyses. There was a decline in body weight predating motor symptom onset (n = 756, 0.70 ± 0.03% decrease per year, p < 0.001). Weight decline accelerated in the decade preceding death (n = 456, 2.18 ± 0.31% decrease per year, p < 0.001). DBS patients showed a weight increase of 2.0 ± 0.33% at 1 year following the first DBS lead implant (n = 455) and 2.68 ± 1.1% at 3 years if a contralateral DBS lead was placed (n = 249). The bilateral STN DBS group gained the most weight after surgery during 6 years of follow up (vs bilateral GPi, 3.03 ± 0.45% vs 1.89 ± 0.31%, p < 0.01). An analysis of the DBS cohort with date of death available (n = 72) revealed that post-DBS weight (0-12 months after the first or 0-36 months after the second surgery) was positively associated with survival (R2 = 0.14, p < 0.001). Though PD is associated with significant weight loss, DBS patients gained weight following surgery. Higher post-operative weight was associated with increased survival. These results should be replicated in other cohorts.


Prophylactic Antiepileptic Drug Use and Outcome in the Ethnic/Racial Variations of Intracerebral Hemorrhage Study.
The role of antiepileptic drug (AED) prophylaxis after intracerebral hemorrhage (ICH) remains unclear. This analysis describes prevalence of prophylactic AED use, as directed by treating clinicians, in a prospective ICH cohort and tests the hypothesis that it is associated with poor outcome. Analysis included 744 patients with ICH enrolled in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study before November 2012. Baseline clinical characteristics and AED use were recorded in standardized fashion. ICH location and volume were recorded from baseline neuroimaging. We analyzed differences in patient characteristics by AED prophylaxis, and we used logistic regression to test whether AED prophylaxis was associated with poor outcome. The primary outcome was 3-month modified Rankin Scale score, with 4 to 6 considered poor outcome. AEDs were used for prophylaxis in 289 (39%) of the 744 subjects; of these, levetiracetam was used in 89%. Patients with lobar ICH, craniotomy, or larger hematomas were more likely to receive prophlyaxis. Although prophylactic AED use was associated with poor outcome in an unadjusted model (odds ratio, 1.40; 95% confidence interval, 1.04-1.88; P=0.03), this association was no longer significant after adjusting for clinical and demographic characteristics (odds ratio, 1.11; 95% confidence interval, 0.74-1.65; P=0.62). We found no evidence that AED use (predominantly levetiracetam) is independently associated with poor outcome. A prospective study is required to assess for a more modest effect of AED use on outcome after ICH.


Variation in the Resistance of Japanese Soybean Cultivars to Phytophthora Root and Stem Rot during the Early Plant Growth Stages and the Effects of a Fungicide Seed Treatment.
Soybean cultivars susceptible to Phytophthora root and stem rot are vulnerable to seed rot and damping-off of seedlings and young plants following an infection by Phytophthora sojae. In this study, the disease responses of Japanese soybean cultivars including currently grown main cultivars during the early growth stages were investigated following infections by multiple P. sojae isolates from Japanese fields. The extent of the resistance to 17 P. sojae isolates after inoculations at 14, 21, and 28 days after seeding varied significantly among 18 Japanese and two US soybean cultivars. Moreover, the disease responses of each cultivar differed significantly depending on the P. sojae isolate and the plant age at inoculation. Additionally, the treatment of 'Nattosyo-ryu' seeds with three fungicidal agrochemicals provided significant protection from P. sojae when plants were inoculated at 14-28 days after seeding. These results indicate that none of the Japanese soybean cultivars are completely resistant to all tested P. sojae isolates during the first month after sowing. However, the severity of the disease was limited when plants were inoculated during the later growth stages. Furthermore, the protective effects of the tested agrochemicals were maintained for at least 28 days after the seed treatment. Japanese soybean cultivars susceptible to Phytophthora root and stem rot that are grown under environmental conditions favorable for P. sojae infections require the implementation of certain practices, such as seed treatments with appropriate agrochemicals, to ensure they are protected from P. sojae during the early part of the soybean growing season.


The application research of xTAG GPP multiplex PCR in the diagnosis of persistent and chronic diarrhea in children.
Persistent and chronic diarrhea is difficult to treat, and infection is still the main cause. In this study, we investigate the application value of xTAG gastrointestinal pathogen panel (xTAG GPP) multiplex PCR in the early diagnosis of persistent and chronic diarrhea in children and to understand the epidemiology of intestinal diarrhea pathogens. One hundred ninety-nine specimens were collected from Nanjing Children's Hospital Affiliated to Nanjing Medical University (Nanjing, China). We compared the xTAG GPP multiplex PCR assay with traditional methods (culture, rapid enzyme immunoassay chromatography, and microscopic examination) and performed a statistical analysis. The positive rate of the xTAG GPP multiplex PCR assay of diarrhea specimens from 199 patients was 72.86% (145/199). The virus detection rate was 48.7%, and rotavirus A was the most common organism detected (34.67%), concentrated in winter, and was common in children. The second most common organism detected was norovirus GI/GII (20.6%). The positive rate of this bacteria was 40.2%, and Campylobacter (22.11%, 44/199) was most frequently detected. C. difficile toxins A/B and Salmonella was detected in 44 and 17 samples, respectively. Infections with Shigella occurred 4 times, and E. coli O157 was only detected once. Three samples were parasitic (1.51%), two samples were positive for Entamoeba histolytica, and one was positive for Cryptosporidium. Adenovirus 40/41, STEC, ETEC, Giardia, Yersinia enterocolitica and Vibrio cholerae were not detected. In total, 86 (43.2%) infected specimens with a single pathogen were detected. There were 59 coinfections (29.65% of the samples) of viruses and/or bacteria and/or parasites. Coinfections involved 49 double infections (24.62%), 9 triple infections (4.52%) and 1 quadruple infections (0.5%). Norovirus GI/GII was found to have the highest involvement, with 32 coinfections (16.08%). The xTAG GPP multiplex PCR assay is simple, sensitive, and specific and can be used as a quick way to diagnose persistent and chronic diarrhea in children.


Effect of lighting programs during the pullet phase on skeletal integrity of egg-laying strains of chickens.
Egg-laying strains of chickens are highly susceptible to osteoporosis, a noninfectious disease characterized by a decrease in structural bone as hens age. To minimize the onset of osteoporosis, it was hypothesized that a delay in sexual maturity may allow a pullet to develop a stronger skeletal frame before egg laying, leading to improved skeletal mineralization at end of lay. One management tool that can easily be implemented by pullet growers to delay sexual maturity is length of photoperiod. The objective of the current study was to determine whether lighting programs used during the pullet phase of egg-laying strains of chickens can be manipulated to allow for improved skeletal mineralization in laying hens at end of lay. Two experiments were conducted in which 1,000 pullets/experiment were exposed to 1 of 3 varying step-down lighting programs (2 to 17 wk of age), referred to as rapid, moderate, and slow. For both experiments, 2 strains of chickens were used. Experiment 1 compared the Hy-Line W-36 with the Hy-Line W-98, and experiment 2 compared the Hy-Line Brown with the Hy-Line W-98. At 66 wk of age, all hens remaining in the study were weighed individually and the drum stick and wing were retrieved for determination of bone mineralization and bone size traits. Bone data were analyzed using an analysis of covariance with BW as the covariant, and BW was analyzed as an ANOVA. Skeletal frame development was affected by lighting regimen. Pullets exposed to the slow lighting photoperiod had longer bones and more bone area (experiment 2) than those exposed to the rapid photoperiod, most likely because of a delay in bone growth plate closure, which occurs at sexual maturity. However, this delay in sexual maturity, as indicated by longer bones, did not improve bone mineralization at 66 wk of age. It was concluded that pullet lighting regimen had little effect on bone mineralization at end of lay.


[Clinical outcomes of stenting for malignant bowel obstruction in terminally ill cancer patients].
We evaluated the effects of stenting for malignant bowel obstruction in terminally ill cancer patients. Six terminally ill cancer patients with malignant bowel obstruction underwent gastrointestinal stenting at our department from November 2010 to October 2012. Stent insertion was successful and abdominal symptoms improved in all cases. Oral intake improved in 4 cases. Descending colon perforation occurred in 1 case. The survival time ranged between 10 and 184 days( median, 71.5 days). The palliative performance status (PPS) improved in 4 cases, and the survival time was extended as assessed by the palliative prognostic index (PPI). In cases with a PPI of were more than 6.0, namely cases for which the estimated survival time was less than 3 weeks, survival time and oral intake did not change. These findings suggest that gastrointestinal stenting is clinically useful for malignant obstruction and improving the PPS and prognosis in terminally ill patients with malignant bowel obstruction.


Interleukin-1beta mediates endotoxin- and tumor necrosis factor alpha-induced RGS16 protein expression in cultured cardiac myocytes.
Endotoxin (LPS)-induced cardiac failure is associated with an up-regulation of RGS16 protein expression and repression of phospholipase C activity in vivo. Since the release of pro-inflammatory cytokines plays an important role in mediating LPS-induced myocardial dysfunction, we examined the effect of recombinant cytokines on the expression of RGS16 protein in neonatal cardiac myocytes. Myocytes in culture were treated with 50 ng/ml recombinant tumor necrosis factor alpha (TNFalpha), 2 ng/ml interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interferon gamma (IFNgamma) or diluent (NaCl) for 24 h. Before stimulation with LPS (4 micro g/ml for 24 h) cells were treated with 200 ng/ml interleukin 1-receptor antagonist (IL-1ra), 500 ng/ml soluble TNF receptor (sTNFr), or NaCl for 1 h. Isolated membrane proteins were used for Western blot analysis. Cell-associated and secreted IL-1beta and TNFalpha protein content were determined in myocyte protein homogenates and cell culture supernatants by ELISA immunoblotting 3, 6, 24, 48 and 72 h after treatment with LPS. IL-1beta (1.75-fold) and TNFalpha (1.62-fold) but not IL-6 and IFNgamma induced RGS16 protein expression. LPS stimulated intracellular IL-1beta expression within 6 h (847.1+/-172.9 pg/3x10(6) cells) followed by an increase in extracellular secretion up to 70.8+/-8.1 pg/3x10(6) cells after 48 h. In contrast, intracellular protein concentrations of TNFalpha were almost not detectable (0.03+/-0.01 pg/3x10(6) cells), but extracellular secretion was induced by LPS with a maximum at 6 h (653.9+/-36.3 pg/3x10(6) cells). The LPS-induced increase in RGS16 (1.6-fold) was blunted by IL-1ra but not by TNFalpha scavenging. Interestingly, both, the IL-1beta- and TNFalpha-effect could be blocked by IL-1ra, indicating that also the TNFalpha-induced RGS16 expression is mediated by IL-1. We therefore conclude that LPS induces RGS16 protein expression by activation of the cytokine IL-1beta in cardiac myocytes. Our data substantiate the role of IL-1beta as an important mediator in LPS-induced cardiac failure.


Real-time monitoring on the adsorption process of salicylic acid onto chitosan membrane using dielectric spectroscopy: macroscale concentration polarization and dynamics.
The adsorption process of salicylic acid (SA) onto chitosan membrane is monitored in real time by the dielectric relaxation spectroscopy (DRS) method. A unique dielectric relaxation, which is related to the macroscale concentration polarization layers (CPLs) in the SA solution caused by the adsorption, is observed. By modeling the measured systems composed of the membrane, the CPLs, and the SA solution, the dielectric spectra are analyzed systematically on the basis of the interfacial polarization theory. The parameters about the constituent phases, i.e., the dielectric constant εm and the conductivity κm of the chitosan membrane, the conductivity distribution (κ1 to κ2), and the thickness dCPL of the CPL, are obtained. The time-dependent εm and κm give insight into the microstate of the chitosan membrane during the adsorption. Furthermore, the time evolution of the conductivity gradient of the CPL, Δκ/dCPL, is combined to interpret the adsorption mechanism. It is suggested that the noninvasive dielectric monitoring may be applied to many adsorption and release processes.


Directional tortuosity as a predictor of modulus damage for vertebral cancellous bone.
There are many methods used to estimate the undamaged effective (apparent) moduli of cancellous bone as a function of bone volume fraction (BV/TV), mean intercept length(MIL), and other image based average microstructural measures. The MIL and BV/TV are both only functions of the cancellous microstructure and, therefore, cannot directly account for damage induced changes in the intrinsic trabecular hard tissue mechanical properties. Using a nonlinear finite element (FE) approximation for the degradation of effective modulus as a function of applied effective compressive strain, we demonstrate that a measurement of the directional tortuosity of undamaged trabecular hard tissue strongly predicts directional effective modulus (r2>0.90) and directional effective modulus degradation (r2>0.65). This novel measure of cancellous bone directional tortuosity has the potential for development into an anisotropic approach for calculating effective mechanical properties as a function of trabecular level material damage applicable to understanding how tissue microstructure and intrinsic hard tissue moduli interact to determine cancellous bone quality.


[Ultrasonography in the diagnosis of hepatic malignant cystic tumors].
To evaluate the clinical application of gray scale and color Doppler sonography in the diagnosis of hepatic malignant cystic tumors. Characteristics of gray scale and color Doppler sonography were studied in 16 cases of malignant hepatic tumors confirmed by pathology. Tumor size, shape, number of lesion, thickness of cystic wall and echogenecity of the lesion were observed with gray scale sonography. Blood supply of the tumor and its velocity were observed with Color Doppler sonography. One single lesion was common in primary malignancy while multiple lesions signified metastasis. Sonographic findings revealed that the shape of the tumor was spheroid in 8 cases, irregular in 5 and leaf-shaped in 3, with the diameter varying from 1.9 cm to 13.6 cm. Sonography showed malignant cystic tumor with irregular thick wall in 15 cases, multiple septa in 7 cases and papillary projections in 6 on gray scale. Color Doppler flow signal was detected in the irregular thick wall, multiple septa or papillary projections in 14 cases, of which the arterial blood flow signals were demonstrated in 13. Color Doppler is able to clearly detect the blood flow signals in the irregular thick wall, multiple septa or papillary projections, providing an important sign for the diagnosis of hepatic malignant cystic tumors.


Differences in orofacial muscle strength according to age and sex in East Asian healthy adults.
The purpose of this study was to identify differences in orofacial muscle strength according to age and sex in healthy East Asian adults. A total of 382 subjects participated in this study (age range, 20-93 yrs). They were divided into two groups according to sex (male, n = 192; female, n = 190). The two groups were further divided on the basis of age into young (20-39 yrs), middle-aged (40-59 yrs), old (60-79 yrs), and very old (>80 yrs) groups. Assessments were performed using the Iowa Oral Performance Instrument. Measures included the anterior tongue elevation pressure, posterior tongue elevation pressure, buccodental pressure, and lip pressure. All measures were higher in the male than in the female subjects (P < 0.001). The male subjects showed noticeably lower tongue strength in the old and very old groups relative to the young and middle-aged groups (P < 0.01); the female subjects showed a similar result in the very old group as compared with all younger groups. Significant age-related differences in orofacial muscle strength were observed mainly of the tongue musculature. The male subjects had significantly lower tongue strength in the seventh decade or older as compared with the younger individuals, whereas in the female subjects, a similar result was noted, although tongue strength was not significantly lower until the ninth decade.


An ERP investigation of location invariance in masked repetition priming.
In an experiment combining masked repetition priming and the recording of event-related potentials (ERPs) the location of prime stimuli relative to centrally located target words was manipulated. Prime words could appear at the same location as targets or shifted one letter position to the right or to the left. Repetition priming effects (amplitude differences across the repeat vs. unrelated prime conditions) were found in a series of ERP components starting at around 100 msec posttarget onset. The earliest of these, the N/P150 component, was found to be sensitive to prime location. Repetition priming was only apparent with centrally located primes in this component. Repetition priming effects in later components (N250 and N400), on the other hand, were not affected by prime location. The results are interpreted in terms of location-specific letter detectors that map onto a higher level, location-invariant orthographic code for printed words.


What Is Wrong with Pertussis Vaccine Immunity? Why Immunological Memory to Pertussis Is Failing.
Memory responses seen after whole-cell pertussis (wP) and acellular pertussis (aP) vaccine priming are different and reflect better long-term protection against pertussis disease seen with the whole-cell vaccines. Although acellular vaccines generate higher levels of antigen-specific IgG to the antigens included in the aP vaccines, there are many more pertussis antigens included in whole-cell vaccines. Acellular vaccine priming is associated with skewing of the immune response to a more Th2-like response, whereas whole-cell priming is associated with a Th1/Th17 response. Repeated booster doses of acellular vaccine in children primed with acellular vaccine has been shown to result in progressively shorter duration of protection against disease. This may be explained by the generation of higher levels of antigen-specific IgG4, which does not bind complement and leads to a suboptimal inflammatory response and impaired phagocytosis and antimicrobial defense. In contrast, whole-cell priming followed by aP vaccine boosters results in better opsonization, phagocytosis, and complement mediated killing through the preferential induction of IgG1.


Hypoxia-Inducible Factor and Oxygen Biology in the Kidney.
Kidney tissue hypoxia is detected in various kidney diseases and is considered to play an important role in the pathophysiology of both AKI and CKD. Because of the characteristic vascular architecture and high energy demand to drive tubular solute transport, the renal medulla is especially prone to hypoxia. Injured kidneys often present capillary rarefaction, inflammation, and fibrosis, which contribute to sustained kidney hypoxia, forming a vicious cycle promoting progressive CKD. Hypoxia-inducible factor (HIF), a transcription factor responsible for cellular adaptation to hypoxia, is generally considered to protect against AKI. On the contrary, consequences of sustained HIF activation in CKD may be either protective, neutral, or detrimental. The kidney outcomes seem to be affected by various factors, such as cell types in which HIF is activated/inhibited, disease models, balance between two HIF isoforms, and time and methods of intervention. This suggests multifaceted functions of HIF and highlights the importance of understanding its role within each specific context. Prolyl-hydroxylase domain (PHD) inhibitors, which act as HIF stabilizers, have been developed to treat anemia of CKD. Although many preclinical studies demonstrated renoprotective effects of PHD inhibitors in CKD models, there may be some situations in which they lead to deleterious effects. Further studies are needed to identify patients who would gain additional benefits from PHD inhibitors and those who may need to avoid them.


Ampullary carcinoma associated with multiple duodenal villous adenomas.
A 39-year old Asian with multiple duodenal villous adenomas and an adenocarcinoma arising from one of these tumors is described. The rarity of villous adenomas at this site is stressed and their tendency to undergo malignant change reviewed. Immunoperoxidase studies using carcinoembryonic antigen (CEA) antiserum were positive in high dilutions (1 in 8,000) in the carcinoma and the largest adenoma. This stain would appear to show functional malignancy before histological evidence of malignancy is found.


Million-fold Relaxation Time Enhancement across a Series of Phosphino-Supported Erbium Single-Molecule Magnets.
Maintaining strong magnetic anisotropy in the presence of collective spin interactions has become a defining challenge in the advancement of single-molecule magnet (SMM) research. Herein we demonstrate effective decoupling of these often competing design goals in a series of new phosphino-supported SMMs containing the anisotropic [Er(COT)]+ (COT2- = cyclooctatetraene dianion) subunit. Across this series, a magnetic nuclearity increase from 1 to 2 and subsequent optimization of the relative local anisotropy axis orientation results in dramatic improvements to the long time scale behavior. Specifically, we observe a 6 orders of magnitude increase in relaxation time at 2 K and a consequent open magnetic hysteresis up to 6 K. This drastic scaling of the magnetic dynamics tracks monotonically with the introduction and approach to parallel of the angle between intramolecular anisotropy axes. These results illustrate the powerful implications of fully controlling direction and magnitude of anisotropy in the design of scalable SMMs.


Reducing the use of carcinogens: the Massachusetts experience.
Toxics use reduction (TUR) is one part of a comprehensive cancer prevention strategy. TUR emphasizes reducing the use of cancer-causing chemicals by improving manufacturing processes and identifying and adopting safer alternatives. This analysis draws on 20 years of data collected from industries reporting to the Massachusetts Toxics Use Reduction Act (TURA) program to assess trends in the use and release of chemicals associated with cancer. We used a master list of known and suspected carcinogens developed from authoritative sources and a list of carcinogens grouped by their association with 11 cancer sites to analyze trends in use and release of chemicals by industrial facilities reporting to the TURA program from 1990 to 2010. The trend analysis shows that reported use and releases of carcinogens by these Massachusetts companies have decreased dramatically over time. Reported use declined 32% from 1990 to 2010, and reported releases declined 93% from 1991 to 2010 (1991 is when additional industrial sectors, including electric utilities, were phased into the program). Particularly large reductions were achieved in the use of trichloroethylene, perchloroethylene and cadmium and cadmium compounds. The analysis of groups of chemicals associated with specific cancer sites shows similar trends. Important opportunities for further reductions in many carcinogens, including formaldehyde, hexavalent chromium, and a variety of halogenated compounds are identified. Continued work to minimize the use of carcinogens can help to reduce the burden of cancer in Massachusetts and elsewhere.


Characterization of insulin-like growth factor-binding protein in ovine amniotic fluid.
We have characterized an insulin-like growth factor (IGF)-binding protein present in ovine amniotic fluid. Using an activated charcoal-binding assay, whole amniotic fluid specifically bound approximately 20-30% of 125I-labelled human (h) IGF-II added, while the binding of 125I-labelled hIGF-I was minimal. Radioimmunoassay for IGF-I or -II in ovine biological fluids showed that values in amniotic fluid were 9- to 13-fold less than in fetal plasma, while gel filtration of amniotic fluid on Sephadex G-50 eluted with 1 mol acetic acid/l revealed no additional binding activity which had been complexed to IGFs at neutral pH. Together, these observations suggest that the binding activity in amniotic fluid is largely unsaturated. Competition studies for the displacement of 125I-labelled IGF-II binding to amniotic fluid by increasing amounts of unlabelled IGF-I or -II, using the charcoal assay, showed that IGF-II was 30-fold more potent than IGF-I. Scatchard analysis revealed a single class of binding site for IGF-II, with a binding affinity of 0.68 +/- 0.18 litres/nmol (mean +/- S.D., n = 3). Ligand blot analysis of amniotic fluid by separation on 8% SDS-PAGE, transfer to nitrocellulose membranes, incubation with 125I-labelled IGF-II and autoradiography revealed a single band of IGF-binding protein with approximate molecular size of 38 kDa. Additional IGF-binding species of 20, 28, 48 and greater than 180 kDa were present in ovine fetal plasma. Separation of amniotic fluid on Concanavalin A-Sepharose revealed that it had little carbohydrate content. These results show that ovine amniotic fluid contains an unsaturated, non-glycosylated IGF-binding protein with high affinity for IGF-II.(ABSTRACT TRUNCATED AT 250 WORDS)


Early cochlear implantation in children allows normal development of central auditory pathways.
The goal of this study was to determine whether there is a sensitive period during early development when a cochlear implantation can occur into a minimally degenerate and/or highly plastic central auditory system. Our measure of central auditory deprivation was latency of the P1 auditory evoked potential, whose generators include auditory thalamocortical areas. Auditory evoked potentials were recorded in 18 congenitally deaf children who were fitted with cochlear implants by 3.5 years of age. The P1 latencies of the children with implants were compared with the P1 latencies of their age-matched peers with normal hearing. There was no significant difference between the P1 latencies of the children with implants and the children with normal hearing. The present results suggest that early implantation occurs in a central auditory system that is minimally degenerate and/or highly plastic. Studies are ongoing to assess the consequences to the developing central auditory system of initiating electrical stimulation at later ages.


Cost-effective analysis of unilateral vestibular weakness investigation.
To evaluate the cost-effectiveness of obtaining a magnetic resonance imaging (MRI) in patients with abnormal electronystagmography (ENG) or videonystagmography (VNG) results. Retrospective chart review. Academic specialty center. Patients presenting with vertigo between January 1, 2010, and August 30, 2013. Patients who fit the following abnormal criteria were included in the study: unilateral caloric weakness (≥20%), abnormal ocular motor testing, and nystagmus on positional testing. Patients with abnormal findings who then underwent MRI with gadolinium were evaluated. Of the 1,996 charts reviewed, there were 1,358 patients who met the inclusion criteria. The average age of these patients was 62 years (12-94 yr). The male:female ratio was approximately 1:2. Of the 1,358 patients, 253 received an MRI with the following pathologies: four vestibular schwannomas, three subcortical/periventricular white matter changes suspicious for demyelinating disease, four acute cerebellar/posterior circulation infarct, two vertebral artery narrowing, one pseudomeningocele of internal auditory canal, and two white matter changes indicative of migraines. The positive detection rate on MRI was 5.5% based on MRI findings of treatable pathologies causing vertigo. Average cost of an MRI is $1,200, thereby making the average cost of identifying a patient with a positive MRI finding $15,180. In our study, those patients with a positive MRI had a constellation of symptoms and findings (asymmetric sensorineural hearing loss, tinnitus, vertigo, and abnormal ENG/VNG). Cost-effectiveness can be improved by ordering an MRI only when clinical examination and VNG point toward a central pathology. Clinical examination and appropriate testing should be factored when considering the cost-effectiveness of obtaining an MRI in patients with abnormal ENG/VNG findings.


Laparoendoscopic single-site surgery in inguinal hernia repair.
Laparoendoscopic single-site surgery (LESS) for laparoscopic inguinal hernia repair (IHR) offers the potential for excellent cosmetic outcomes and maximization of the inherent advantages of minimally invasive surgery. LESS IHR is associated with a steep learning curve, which is attributable to both the IHR technique itself and the single-site technique. The technical obstacles in the single-site technique may be mitigated by employing certain maneuvers and strategies that minimize clashing between instruments and improve freedom of movement. The current literature consistently points out the inherent challenges in LESS IHR, with its longer operative time compared to that of conventional laparoscopic IHR. LESS IHR performed by capable operators has comparable complication rates, duration of hospital stay, and incidence of recurrence as conventional laparoscopic IHR. LESS IHR is both feasible and safe. Given its excellent cosmetic outcome, it is likely to be sought by younger patients who are concerned with scar formation. The use of robotics may bypass the technical challenges in LESS, but cost considerations in their usage will likely persist.


Successful management of H1N1 related severe acute respiratory distress syndrome with noninvasive positive pressure ventilation.
Acute respiratory distress syndrome (ARDS) is a life threatening complication of H1N1 pneumonia. According to the Berlin conference guidelines, severe ARDS requires management with early invasive mechanical ventilation. Whether noninvasive positive pressure ventilation (NIPPV) should be attempted in patients with H1N1 pneumonia is still a matter of debate. We report the case of one patient with severe ARDS without other organ failure. The patient was managed successfully using NIPPV. Endotracheal intubation was avoided and the patient was discharged from the intensive care unit (ICU) after 10 days with a successful outcome. NIPPV can be useful in patients with isolated severe H1N1 ARDS provided early improvement of the oxygenation parameters is achieved. Patients with multiple organ failure or with persistent severe hypoxemia under noninvasive ventilation should be electively intubated and started on invasive mechanical ventilation.


Fabrication of Polymer-Protein Hybrids.
Rapid developments in organic chemistry and polymer chemistry promote the synthesis of polymer-protein hybrids with different structures and biofunctionalities. In this feature article, recent progress achieved in the synthesis of polymer-protein conjugates, protein-nanoparticle core-shell structures, and polymer-protein nanogels/hydrogels is briefly reviewed. The polymer-protein conjugates can be synthesized by the "grafting-to" or the "grafting-from" approach. In this article, different coupling reactions and polymerization methods used in the synthesis of bioconjugates are reviewed. Protein molecules can be immobilized on the surfaces of nanoparticles by covalent or noncovalent linkages. The specific interactions and chemical reactions employed in the synthesis of core-shell structures are discussed. Finally, a general introduction to the synthesis of environmentally responsive polymer-protein nanogels/hydrogels by chemical cross-linking reactions or molecular recognition is provided.


International collaboration to enhance the fight against HIV/AIDS: report of a consultative meeting between the University of Buea in Cameroon and the Goldfarb School of Nursing in the USA.
HIV/AIDS is a major public health pandemic affecting the development, survival and life of young people both in Cameroon and the USA. Youths are more adaptive to change and less hindered by prejudice than adults. Student-to-student peer mentoring is a non-formal way for students to learn new life skills and different cross-cultural values. We report on a two-day consultative meeting in 2010 on developing international collaboration for the fight against HIV/AIDS between Cameroonian and USA nursing students. We used adult learning approaches consisting of presentations, discussions, questions and answer sessions, role plays and demonstrations. Deliberations and resolutions from the consultative meeting enabled the Vice-Chancellor of the University of Buea to sign a memorandum of understanding with the Goldfarb School of Nursing in the USA on HIV/AIDS international collaboration paving the way forward for more developmental health projects in this domain.


Agenesis of the corpus callosum and gyral malformations are frequent manifestations of nonketotic hyperglycinemia.
A 2-week-old infant who presented with myoclonic encephalopathy had biochemical abnormalities consistent with nonketotic hyperglycinemia. Cranial CT showed agenesis of the corpus callosum, gyral malformation, and ventricular enlargement. Similar brain abnormalities occurred in 9 of 15 previously reported patients. Including this patient, agenesis of the corpus callosum appeared in 6 of 15 patients, gyral malformation in 6 of 14, ventricular enlargement in 5 of 15, and cerebellar hypoplasia in 2 of 16. Nonketotic hyperglycinemia thus joins a growing list of inborn errors of metabolism associated with brain malformations.


Thirty years of polyamine-related approaches to cancer therapy. Retrospect and prospect. Part 1. Selective enzyme inhibitors.
As soon as the natural polyamines (PAs), putrescine (Put), spermidine (Spd) and spermine (Spm), were recognized as ubiquitous constituents of eukaryotic cells, their involvement in growth-related processes attracted particular interest. The high activities of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) in rapidly growing tissues and cells, particularly in tumour cells, suggested PA biosynthesis as a target for antineoplastic therapy. In the course of the years selective inhibitors have been developed for literally all enzymes of PA metabolism. Some became important as tools in the elucidation of the PA metabolic system, but only few of them were efficient as inhibitors of tumour growth. A major reason for the inefficacy of selective enzyme inhibitors as anticancer drugs is the sophistication of the system, which regulates intracellular PA pools. Selective blockade of a single enzyme induces changes of metabolism and transport, which compensate for the deficit. The selective impairment of tumour growth is in addition hampered by the ubiquitous occurrence of the PAs, their importance in normal functions of nearly all mammalian cells, and the ability or the mammalian organism to utilize exogenous (gastrointestinal) PAs. Among the inhibitors of PA-related enzymes, the ODC inactivator (R, S)-2-(difluoromethyl)ornithine (DFMO) became most famous. Although it was disappointing in most therapeutic attempts to use it as single drug, it has--based on its low toxicity--considerable potential in cancer chemoprevention, and it turned out to be a highly efficient anti-trypanosome agent. Very likely DFMO is suitable to improve the efficacy of some of the current cytotoxic drugs, and it may allow one to create new therapies in combination with other PA-directed drugs. Some of the less selective enzyme inhibitors, particularly those, which inhibit two or more enzymes of PA metabolism, appear to have had a chance to become practically useful, but they have not been developed energetically. Disregarding DFMO, the AdoMetDC inhibitor SAM486A is the only compound for which clinical trials were published. The future of this drug is unclear at present; presumably phase III clinical trials have been discontinued. One of the lessons that had to be learned from the work on selective enzyme inhibitors was that PA metabolism is a much more difficult target, than has been expected on the basis of the simplicity of the PA structures, and the simple reactions involved in their biosynthesis. In order to inhibit tumour growth several reactions or regulatory functions of PA metabolism have to be impaired at the same time. Recent efforts devoted to the development new types of anticancer drugs, which are based on the perturbation of PA metabolism by structural analogues of the natural PAs, take this message into account. These approaches are the topic of the 2nd part of this overview.


A Crosslinked Nucleic Acid Nanogel for Effective siRNA Delivery and Antitumor Therapy.
Functional siRNAs are employed as cross-linkers to direct the self-assembly of DNA-grafted polycaprolactone (DNA-g-PCL) brushes to form spherical and nanosized hydrogels via nucleic acid hybridization in which small interfering RNAs (siRNAs) are fully embedded and protected for systemic delivery. Owing to the existence of multivalent mutual crosslinking events inside, the crosslinked nanogels with tunable size exhibit not only good thermostability, but also remarkable physiological stability that can resist the enzymatic degradation. As a novel siRNA delivery system with spherical nucleic acid (SNA) architecture, the crosslinked nanogels can assist the delivery of siRNAs into different cells without any transfection agents and achieve the gene silencing effectively both in vitro and in vivo, through which a significant inhibition of tumor growth is realized in the anticancer treatment.


The Emerging Role of Ferroptosis in Sepsis.
Ferroptosis is a novel form of cell death characterized by the iron-dependent accumulation of lipid peroxides and is different from other types of cell death. The mechanisms of ferroptosis are discussed in the review, including System Xc-, Glutathione Peroxidase 4 pathway, Ferroptosis Suppressor Protein 1 and Dihydroorotate Dehydrogenase pathway. Ferroptosis is associated with the occurrence of various diseases, including sepsis. Research in recent years has displayed that ferroptosis is involved in sepsis occurrence and development. Iron chelators can inhibit the development of sepsis and improve the survival rate of septic mice. The ferroptotic cells can release damage-associated molecular patterns and lipid peroxidation, which further mediate inflammatory responses. Ferroptosis inhibitors can resist sepsis-induced multiple organ dysfunction and inflammation. Finally, we reviewed ferroptosis, an iron-dependent form of cell death that is different from other types of cell death in biochemistry, morphology, and major regulatory mechanisms, which is involved in multiple organ injuries caused by sepsis. Exploring the relationship between sepsis and ferroptosis may yield new treatment targets for sepsis.


Migration and Precipitation of Platinum in Anion-Exchange Membrane Fuel Cells.
Despite the recent progress in increasing the power generation of Anion-exchange membrane fuel cells (AEMFCs), their durability is still far lower than that of Proton exchange membrane fuel cells (PEMFCs). Using the complementary techniques of X-ray micro-computed tomography (CT), Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray (EDX) spectroscopy, we have identified Pt ion migration as an important factor to explain the decay in performance of AEMFCs. In alkaline media Pt+2 ions are easily formed which then either undergo dissolution into the carbon support or migrate to the membrane. In contrast to PEMFCs, where hydrogen cross over reduces the ions forming a vertical "Pt line" within the membrane, the ions in the AEM are trapped by charged groups within the membrane, leading to disintegration of the membrane and failure. Diffusion of the metal components is still observed when the Pt/C of the cathode is substituted with a FeCo-N-C catalyst, but in this case the Fe and Co ions are not trapped within the membrane, but rather migrate into the anode, thereby increasing the stability of the membrane.


Immune response in bovine neosporosis: Protection or contribution to the pathogenesis of abortion.
Neospora caninum is a protozoan parasite with a preference for cattle and dogs as hosts. When N. caninum infection occurs in cattle it induces abortion, bovine neosporosis being a main cause of abortion worldwide. In dairy cattle, the economic burden of neosporosis-associated abortion is so great that it might results in closure of a farm. However, not all infected cows abort and it is not yet understood why this occurs. At present there is no effective treatment or vaccine. This review provides insights on how immune response against the parasite determines protection or contribution to abortion. Aspects on markers of risk of abortion are also discussed. Humoral immune responses are not protective against N. caninum but seropositivity and antibody level can be good markers for a diagnosis of bovine neosporosis and its associated abortion risk. In addition, humoral mechanisms against N. caninum infection and abortion differ in pure-breed and cross-breed pregnant dairy and beef cattle. Concentrations of Pregnancy Associated glycoprotein -2 (PAG-2) can also be used to predict abortion. A partially protective immune response encompasses increased IFN-γ expression, which has to be counterbalanced by other cytokines such as IL-12 and IL-10, especially towards the end of pregnancy. Although IFN-γ is required to limit parasite proliferation a critical threshold of the IFN-γ response is also required to limit adverse effects on pregnancy. In clinical terms, it may be stated that IFN-γ production and cross-breed pregnancy can protect Neospora-infected dairy cows against abortion.


Emerging drugs for epilepsy and other treatment options.
Epilepsies are amongst the most frequent chronic neurological conditions. Patients suffer from spontaneously recurring seizures because of sudden extensive electrical gray matter discharges. Although the current drug therapy allows many patients at least some degree of a satisfying course of the disease, a substantial number of patients remain without adequate seizure control. Reasons are either refractoriness to anticonvulsant drugs or intolerable drug-related side effects. Epilepsy surgery should be considered in these cases as possible treatment option. Nevertheless, a considerable rate of patients will not be suitable candidates or continue to have seizures despite surgery. Therefore there is a substantial need for better antiepileptic drugs. The aim of this review is to highlight currently emerging different treatment approaches which may ameliorate the perspectives of patients with difficult-to-treat epilepsies.


Promising new causal explanations for obesity and obesity-related diseases.
Current explanations for obesity center around a predisposition in genotype and phenotype, possibly triggered by an inflammatory process or event, and exacerbated by environmental and psychological factors. It is likely that a variety of physiologic factors may act in combination to produce clinical obesity. Leptin resistance may be an important neurochemical cause of obesity; elevated leptin levels have been correlated with weight gain over extended time periods. Genetic studies support the postulate that a gene originating with our cave-dwelling ancestors, critical to survival when food was scare, has evolved into a trigger for obesity and related diseases. A variety of biochemical markers are prevalent in obesity and obesity-linked disease states. C-reactive protein, interleukin-6, and others are elevated in obesity, supporting the hypothesis that inflammation plays a role in the condition. Tumor necrosis factor-alpha is overexpressed in obesity and diabetes, suggesting that it may be part of the link between the 2 conditions.


An Evaluation of the Content of Canadian Radiology Fellowship Websites.
Prospective radiology fellows utilize the internet to apply for radiology fellowship programs. The aim of this study was to analyze the online content of Canadian radiology fellowship websites. The content of all active Canadian radiology fellowship websites were evaluated using 30 criteria in the following domains: application, recruitment, education and research, clinical work and benefits. Fellowships without websites were excluded from the study. The prevalence of assessed elements was compared to geography and Canadian medical school ranking. We identified 107 active Canadian radiology fellowship programmes, of which 102 university fellowships (95.3%) had dedicated fellowship websites available for analysis. Of these 102 programs, the median score was 13/30 (43.0%). Websites of fellowship programs affiliated with top ranked medical schools contained more of the assessed criteria than middle and lower ranked schools (17.0 vs 13.0 vs 9.0, p < 0.0001)). Geographical difference was identified across Canada with Atlantic and Central Canada fellowship programs having significantly more criteria than Western programs (15.5 vs 16.0 vs 10.0, p < 0.001). Most Canadian radiology fellowship websites are devoid of content pertinent to prospective radiology fellows. Addressing deficiencies in online content may assist programs to inform and recruit residents into radiology fellowship programs.


Association of Body Mass Index and Body Mass Index Change with Mortality in Incident Peritoneal Dialysis Patients.
Although high body mass index (BMI) appears to confer a survival advantage in hemodialysis patients, the association of BMI with mortality in continuous ambulatory peritoneal dialysis (CAPD) patients is uncertain. We enrolled incident CAPD patients and BMI was categorized according to World Health Organization classification for Asian population. BMI at baseline and one year after the initiation of peritoneal dialysis (PD) treatment was assessed to calculate the BMI change (∆BMI). Patients were split into four categories according quartiles of ∆BMI. Kaplan-Meier method and Cox regression proportional hazard analysis were performed to assess the association of BMI on outcomes. A total of 1263 CAPD patients were included, with a mean age of 47.8 ± 15.0 years, a mean BMI of 21.58 ± 3.13 kg/m². During a median follow-up of 25.3 months, obesity was associated with increased risk for cardiovascular diseases (CVD) death (adjusted hazard ratio (AHR) 2.01; 95% CI 1.14, 3.54), but not all-cause mortality. Additionally, patients with more BMI decline (>0.80%) during the first year after CAPD initiation had an elevated risk for both all-cause (AHR: 2.21, 95% CI 1.23-3.95) and CVD mortality (AHR 2.31, 95% CI 1.11, 4.84), which was independent of baseline BMI values.


Effect of surface segregation on the methanol oxidation reaction in carbon-supported Pt-Ru alloy nanoparticles.
Ru and Pt-Ru (Pt:Ru = 1:1) nanoparticles supported on carbon black were prepared by the borohydride reduction method using oleylamine as a stabilizer in an anhydrous ethanol solvent. We investigated the effect of Pt segregation to the surface of alloy nanoparticles on the methanol oxidation reaction (MOR). As-prepared Pt(1)Ru(1)/C showed a narrow size distribution and a relatively uniform particle distribution on a carbon support. However, its electrocatalytic activity toward the MOR was poor due to the high surface concentration of Ru. As duration time of heat treatment at 200 degrees C was increased up to 2 h, the surface composition of Pt atoms was increased without significant particle growth due to thermally induced segregation of Pt atoms, which were revealed by TEM images, X-ray photoelectron spectroscopy (XPS) analysis, changes in the potentials of zero total charge (pztc), and increase in the oxidation charge of "reduced CO(2)". In particular, from the combination of CO adlayer oxidation and "reduced CO(2)" oxidation charges, the increased surface concentration of Pt of alloy catalysts was relatively quantified when compared to its as-prepared state. Cyclic voltammograms in 0.1 M HClO(4) solution with 0.5 M methanol showed that Pt(1)Ru(1)/C annealed for 2 h at 200 degrees C in a flow of mixture gas of Ar and H(2) (5 vol %) had a less positive onset potential for the MOR. These results demonstrate a definitive contribution from segregation of Pt atoms to the MOR activity.


Clinical significance of subcutaneous fat and fascial involvement in juvenile dermatomyositis.
Objectives: Subcutaneous involvement, including calcinosis and panniculitis, is a more common complication in juvenile dermatomyositis (JDM) than in adult dermatomyositis. Magnetic resonance imaging (MRI) is useful for evaluating disease distribution. We investigated the clinical significance of subcutaneous involvement in JDM. Methods: Thighs and hips in 18 newly diagnosed JDM patients were evaluated with fat-suppression MRI. Bilateral muscle, fascial and subcutaneous fat involvement were scored from 0 to 8 points according to the severity of distribution on MRI. Associations between clinical manifestations, serum muscle enzymes, and MRI scores were also evaluated. Results: Abnormal MRI findings in muscle, fascia and subcutaneous fat were observed in 18, 18, and 10 patients, respectively. Subcutaneous fat scores were significantly higher in early-diagnosed JDM patients (diagnosed less than 2 months from onset) than in late-diagnosed JDM patients (diagnosed later) (p = .025). Serum aldolase was elevated in all patients, although only eight demonstrated elevated serum creatine phosphokinase. Serum aldolase was significantly correlated with MRI scores for subcutaneous fat (p < .0001, ρ = .787) and fascia (p = .013 ρ = 0.574), but not muscle. Additionally, serum aldolase was significantly correlated with serum triglycerides (p = .009, ρ = 0.629). Conclusion: Subcutaneous fat involvement is a characteristic finding in early-diagnosed JDM and correlates with elevated serum aldolase.


Two Cases of Catastrophic AAA Rupture in Young Women with Systemic Lupus Erythematosus.
We present two cases of young women with a past medical history significant for systemic lupus erythematosus (SLE), who presented to the Emergency Department with a ruptured abdominal aortic aneurysm (AAA). These cases are of particular interest because the patients did not fit the typical demographic for patients who present with a ruptured AAA. Based on these cases and a review of the relevant literature, ED providers should maintain a higher index of suspicion for AAA rupture in patients with autoimmune diseases, especially SLE.


Personnel Scheduling during the COVID-19 Pandemic: A Probabilistic Graph-Based Approach.
Effective personnel scheduling is crucial for organizations to match workload demands. However, staff scheduling is sometimes affected by unexpected events, such as the COVID-19 pandemic, that disrupt regular operations. Limiting the number of on-site staff in the workplace together with regular testing is an effective strategy to minimize the spread of infectious diseases like COVID-19 because they spread mostly through close contact with people. Therefore, choosing the best scheduling and testing plan that satisfies the goals of the organization and prevents the virus's spread is essential during disease outbreaks. In this paper, we formulate these challenges in the framework of two Mixed Integer Non-linear Programming (MINLP) models. The first model aims to derive optimal staff occupancy and testing strategies to minimize the risk of infection among employees, while the second is aimed only at optimal staff occupancy under a random testing strategy. To solve the problems expressed in the models, we propose a canonical genetic algorithm as well as two commercial solvers. Using both real and synthetic contact networks of employees, our results show that following the recommended occupancy and testing strategy reduces the risk of infection 25-60% under different scenarios. The minimum risk of infection can be achieved when the employees follow a planned testing strategy. Further, vaccination status and interaction rate of employees are important factors in developing scheduling strategies that minimize the risk of infection.


[Development of bacterial flora in leg ulcer].
In the present study of the microbiological flora of 284 ulcera crurum we found 452 various bacterial strains. 174 (61.3%) of the 284 ulcera crurum were found in women, 110 (38.7%) in men with a predominance in the age group between 70-79 years. Staphylococcus aureus were the most frequent bacteria, with an isolation rate of 22,4%. Furthermore, gram-negative bacteria like pseudomonas (14.6%), proteus (10.2%) were isolated. Besides these other species of the group of enterobacteriaceae must be taken into consideration--especially Enterobacter and Klebsiella. In comparison to the results of bacterial isolation rates reported in the literature of the last 15 years, it is obvious that staph. aureus is most common in the bacterial invasion of ulcera crurum . An increase of isolation rates of pseudomonas and proteus and other gram-negative germs could not be found during the last 10 years. The variety of bacterial species on leg ulcers and the frequent occurrence of mixed flora give evidence of the importance of microbiological diagnostic and antibacterial therapy.


Multiwalled Carbon Nanotubes of Varying Size Lead to DNA Methylation Changes That Correspond to Lung Inflammation and Injury in a Mouse Model.
Diversity in physicochemical properties of engineered multiwalled carbon nanotubes (MWCNTs) increases the complexity involved in interpreting toxicity studies of these materials. Studies indicate that epigenetic changes could be at least partially involved in MWCNTs-induced pro-inflammatory and fibrotic lung pathology. Therefore, we examined distinct methylation changes in response to MWCNTs of varied sizes to identify potential epigenetic biomarkers of MWCNTs exposure and disease progression. C57BL/6 mice were exposed via oropharyngeal instillation to a single dose (50 μg) to one of three differently sized MWCNTs: "narrow short" (NS), "wide short" (WS), and "narrow long" (NL). Vehicle-treated control mice received dispersion media (DM) only. Whole lung lavage fluid (LLF) and lung tissue were collected 24 h and 7 days postexposure to evaluate pro-inflammatory cytokines, epigenetic, or histological responses at acute and subchronic intervals, respectively. Luminometric methylation assay and pyrosequencing were used to measure global DNA methylation as well as promoter methylation of inflammation and fibrosis-related genes, respectively. Pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured using enzyme-linked immunosorbant assay, while airway thickening and interstitial collagen accumulation were measured in 7-day lung tissue using laser scanning cytometry. Distinct patterns of methylation (i.e., IL-1ß, IL-6, and TNF-α) among the different sized MWCNTs at 24 h postexposure corresponded to some pro-inflammatory cytokine measurements from whole LLF. Fibrosis-related gene, Thy-1, was significantly hypermethylated after exposures to WS and NL MWCNTs, while only NL MWCNTs induced significantly lower global DNA methylation. After 7 days, a hierarchy in airway thickness and interstitial collagen deposition was observed: NS < WS < NL. However, only airway thickness was significantly greater in the WS and NL MWCNTs-exposed groups than the DM-exposed group. These data suggest that methylation changes could be involved in the initial immune response of inflammation and tissue remodeling that precedes lung disease in response to different MWCNTs sizes.


Neural control of lower airway vasculature. Involvement of classical transmitters and neuropeptides.
1. SP- and CGRP-IR fibres of presumably sensory origin were abundantly located around the vasculature and glands in the laryngotracheal and bronchial mucosae of the pig. A sparse presence of CGRP- and SP-IR nerves in the tracheobronchial smooth muscle layer as well as an atropine-sensitive bronchoconstrictor response to electrical field stimulation suggested that neuropeptides locally released from sensory nerves may be related to vascular or exocrine gland function rather than to bronchial smooth muscle control. In the tracheal mucosa, many VIP-positive perivascular nerve fibres, likely to be of local parasympathetic origin, were present, whereas very few or no such fibres were found in the bronchial mucosa or in the pulmonary vascular bed. A dense innervation of the tracheobronchial and pulmonary vasculature by NPY/DBH-containing perivascular fibres suggested that the sympathetic control of these vascular beds may not only involve NA as transmitter. 2. Mainly sensory axon reflex mechanisms occurred upon systemic capsaicin injection in the pig after pretreatment with a combination of autonomic blocking agents, as revealed by plasma elevations of CGRP- and NKA-LI but not NPY-LI or catecholamines. Repeated capsaicin injections, in the presence of autonomic blocking agents, caused a marked reduction in the elevation of plasma CGRP- and NKA-LI with a clear-cut fall in the bronchial vascular response, suggesting development of tachyphylaxis for local sensory mechanisms. 3. Vasodilatory vagal mechanisms involved different neurotransmitters in the lower airway vasculature of the pig. Thus, local blood flow in the laryngo-tracheal circulation was regulated by cholinergic and non-cholinergic parasympathetic mechanisms and a small capsaicin-sensitive sensory component, while the vagal control of the bronchial circulation seemed to mainly involve capsaicin-sensitive sensory nerves. VIP and ACh were more potent as vasodilators in the laryngo-tracheal compared to the bronchial circulation. Exogenous SP was the most potent vasodilator peptide in the lower airway mucosa. SP and CGRP mimicked capsaicin-induced vasodilatation in the laryngo-tracheal and bronchial circulations. In the pulmonary circulation, vagal activation evoked atropine-sensitive vasoconstriction, probably due to sympathetic reflexes, but not vasodilatation. 4. Both NA and NPY had potent vasoconstrictor effects in the airway mucosa.(ABSTRACT TRUNCATED AT 400 WORDS)


The use of self-gripping (Progrip™) mesh during laparoscopic total extraperitoneal (TEP) inguinal hernia repair: a prospective feasibility and long-term outcomes study.
The use of self-gripping mesh during laparoscopic TEP inguinal hernia repairs may eliminate the need for any additional fixation, and thus reduce post-operative pain without the added concern for mesh migration. Long-term outcomes are not yet prospectively studied in a controlled fashion. Under IRB approval, from January 2011-April 2013, 91 hernias were repaired laparoscopically with self-gripping mesh without additional fixation. Patients were followed for at least 1 year. Demographics and intraoperative data (defect location, size, and mesh deployment time) are recorded. VAS is used in the recovery room (RR) to score pain, and the Carolinas Comfort Scale ™ (CCS), a validated 0-5 pain/quality of life (QoL) score where a mean score of >1.0 means symptomatic pain, is employed at 2 weeks and at 1 year. Morbidities, narcotic usage, days to full activity and return to work, and CCS scores are reported. Sixty two patients, with 91 hernias repaired with self-gripping mesh, completed follow-up at a mean time period of 14.8 months. Seventeen hernias were direct defects (average size 3.0 cm). Mesh deployment time was 193.7 s. RR pain was 1.1/10 using a VAS. Total average oxycodone/acetaminophen (5 mg/325 mg) usage = 5.0 tablets, days to full activity was 1.6, and return to work was 4.2 days. Thirteen small asymptomatic seromas were palpated without any recurrences or groin tenderness, and all seromas resolved by the 6 month visit. Transient testis discomfort was reported in five patients. Urinary retention was 3.2%. Mean CCS™ scores at the first visit for groin pain laying, bending, sitting, walking, and step-climbing were 0.2, 0.5, 0.4, 0.3, and 0.3, respectively. At the first post op visit, 4.8% had symptomatic pain (CCS > 1). At 14.8 months, no patients reported symptomatic pain with CCS scores for all 62 patients averaging 0.02, (range 0-0.43). There are no recurrences thus far. Self-gripping mesh can be safely used during laparoscopic TEP inguinal hernia repairs; our cohort had a rapid recovery, and at the 1-year follow-up visit, there were no recurrences and no patients reported any chronic pain as defined by a CCS™ > 1.


Orthodontics with Customized versus Noncustomized Appliances: A Randomized Controlled Clinical Trial.
This randomized controlled trial aimed to evaluate the duration and outcome quality of orthodontic treatment with a customized fixed appliance system versus a noncustomized system. Patients ( n = 180) were randomized and received orthodontic treatment with the Insignia customized orthodontic system or the Damon Q noncustomized orthodontic system. The allocation sequence was concealed using identical, sequentially numbered, opaque, sealed envelopes. Patients with nonextraction treatment plans were treated by 2 equally experienced orthodontists. Pretreatment and posttreatment plaster casts were made for each patient, and the models were rated using the Peer Assessment Rating (PAR) score. Planning time, treatment duration, and numbers of loose brackets, visits, and complaints were recorded. The examined null hypothesis was that the customized appliance system was not associated with significantly ( P < 0.05) shorter treatment duration compared to a noncustomized appliance. We analyzed 85 patients in the customized group and 89 in the noncustomized group. Treatment duration was 1.29 ± 0.35 y in the customized group and 1.24 ± 0.37 y in the noncustomized group. In the customized group, the PAR score was 23.32 ± 9.15 pretreatment and 5.38 ± 3.75 posttreatment. In the noncustomized group, the PAR score was 21.84 ± 7.95 pretreatment and 5.93 ± 3.58 posttreatment. None of these outcomes significantly differed between groups. On the other hand, the orthodontist had a significant effect on treatment duration, quality of treatment outcome, and number of visits ( P < 0.05). A higher PAR score pretreatment was associated with increased treatment duration, posttreatment PAR, and number of visits ( P < 0.05). Compared to the noncustomized group, the customized group had more loose brackets, a longer planning time, and more complaints ( P < 0.05). The customized orthodontic system was not associated with significantly reduced treatment duration, and treatment quality was comparable between the 2 systems ( ClinicalTrials.gov : NCT01268852).


Manual asymmetry for temporal and spatial parameters in sensorimotor synchronization.
Previous studies suggest a right hemisphere advantage for temporal processing and a left hemisphere advantage for planning of motor actions. In the present study, we studied sensorimotor synchronization of hand reaching movements with an auditory rhythm. Blindfolded right-handed participants were asked to synchronize left and right hand movements to an auditory rhythm (40 vs. 60 vs. 80 bpm) and simultaneously reproduce the amplitude of a previously shown movement. Constant and variable asynchronies and movement amplitude errors were measured. The results showed that (a) constant asynchrony was lesser with the left hand than the right hand and (b) constant and variable amplitude errors were lesser with the right hand than the left hand. We suggest that when hand reaching movements are synchronized with an auditory rhythm, the left hand/right hemisphere system appears relatively specialized in temporally adhering to the rhythm and the right hand/left hemisphere system in performing spatially accurate movements.


The Stroke Self-Efficacy Questionnaire: measuring individual confidence in functional performance after stroke.
The aim was to develop a questionnaire for use by practitioners working in stroke care to measure self-efficacy judgements in specific domains of functioning relevant to individuals following stroke. The prevalence of stroke is set to rise across the developed world especially amongst the elderly population. Recovery and adjustment in the longer term can be affected by many different factors. Current objective measures of functional performance used in many stroke programmes may not fully explain the extent of personal levels of confidence that could ultimately influence outcome. Three separate studies were conducted to develop the Stroke Self-Efficacy Questionnaire. A total of 112 stroke survivors, between 2 and 24 weeks, poststroke participated in the study. Development of the scale was undertaken between 2004 and 2006. The final 13-item Stroke Self-Efficacy Questionnaire was found to have good face validity and feasibility to use in the recovery period following stroke. Cronbach Alpha was 0.90 suggesting good internal consistency, and criterion validity was high compared with the Falls Efficacy Scale, r = 0.803, p < 0.001. The Stroke Self-Efficacy Questionnaire was also able to discriminate between those participants walking and not walking. Preliminary psychometric testing of the new Stroke Self-Efficacy Questionnaire has indicated that it is a valid measure of confidence for functional performance and aspects of self-management relevant for individuals recovering from stroke. The Stroke Self-Efficacy Questionnaire could assist clinicians and researchers working in acute stroke care and rehabilitation to screen levels of confidence of stroke survivors in relation to functional performance and self-management. The Stroke Self-Efficacy Questionnaire could be used as part of battery of stroke outcome measures to provide a more comprehensive overview of factors influencing performance in the individuals recovering from a stroke.