Ten-year experience with pediatric laparoscopic appendectomy--are we getting better?
The purpose of this study was to compare our initial (1994-1997) and recent (2001-2003) experiences in laparoscopic appendectomy (LA). A 2-year (2001-2003) retrospective chart review of cases of appendicitis was performed and compared with data obtained from 1994 to 1997 cases. Operating and anesthetic times as well as postoperative outcomes were analyzed. Cases of conversion to open appendectomy were included in the analysis. Two hundred and thirty-three LA cases from 2001 to 2003 were compared with 119 cases from 1994 to 1997. Operating time decreased significantly from 58 to 47 minutes in acute appendicitis (AA) and from 80 to 58 minutes in perforated appendicitis (PA). Anesthetic time decreased significantly in both AA (82 to 71 minutes) and PA (106 to 84 minutes). There were significant decreases in the conversion rate in PA (23.4% to 3.5%), although no change was seen in AA. In PA, the incidence of postoperative abscess decreased from 36.2% to 16.5%. There was no significant decrease in length of stay, amount of analgesia used, time to resume regular diet, or incidence of wound infections and bowel obstructions. Ten years of experience in LA has resulted in decreases in anesthetic and operating times for AA and PA as well as decreases in the incidence of abscesses and conversion rates.


Direct and enantioselective organocatalytic alpha-chlorination of aldehydes.
The first direct enantioselective catalytic alpha-chlorination of aldehydes has been accomplished. The use of enamine catalysis has provided a new organocatalytic strategy for the enantioselective chlorination of aldehydes to generate alpha-chloro aldehydes, an important chiral synthon for chemical and medicinal agent synthesis. The use of imidazolidinone 3 as the asymmetric catalyst has been found to mediate the halogenation of a large variety of aldehyde substrates with the perchlorinated quinone 1 serving as the electrophilic chlorinating reagent. A diverse spectrum of aldehyde substrates can also be accommodated in this new organocatalytic transformation. The capacity of catalyst 3 to override the inherent bias of resident stereogenicity in the chlorination of enantiopure beta-chiral aldehydes is also described. Catalyst quantities of 5 mol % were generally employed in this study.


Relational utility as a moderator of guilt in social interactions.
The capacity to experience guilt is assumed to benefit individuals, as the rewards of repeated, cooperative interactions are likely to exceed the rewards of acting selfishly. If that assumption is true, the extent to which people experience guilt over interpersonal transgressions should at least partly depend on the utility of another person for the attainment of personal goal(s) through social interaction (relational utility). Three experiments confirmed the relational utility hypothesis by showing that people felt guiltier (a) over excluding someone from a fun game if this person could subsequently distribute more money in a dictator game, (b) over hypothetical social transgressions toward a person who was instrumental to the attainment of a salient goal than toward a person who was not instrumental to the attainment of that goal and toward the same person when no goal was salient, and (c) over a low contribution in a social dilemma game if they were more dependent on their group members for performing well in a subsequent debating contest. Closeness with the other person, differences in severity of the transgression, and strategic motives for expressing guilt were consistently excluded as alternative accounts of the effects. By showing that relational utility may affect guilt, these findings (a) provide support for the individual level function of guilt; (b) extend research on the antecedents of guilt in social interactions, which mainly focused on retrospective appraisals; and (c) bear implications for the status of guilt as a moral emotion.


Carbon Dioxide versus Saline Tissue Expanders: Does It Matter?
Implant-based breast reconstruction is the most common reconstructive technique in the United States. Despite its popularity, saline-based tissue expansion still has its limitations, including lengthy expansion times, large uncomfortable bolus dosing, and frequent percutaneous injections/expansion visits. Ideally, a novel technology would eliminate frequent, percutaneous saline injections and allow patients to perform expansion at home, reducing the disruptive experience of current tissue expansion. Within the past 6 years, the AeroForm tissue expander system has used remotely activated carbon dioxide release as the fill medium instead of saline, eliminating many limitations of traditional tissue expanders. In this article, the authors first review the relevant literature concerning carbon dioxide-based tissue expansion in animal and human models. The authors then analyze the similarities and differences between two groundbreaking human trials (i.e., Patient Activated Controlled Expansion and AirXpanders Patient Activated Controlled Tissue Expander) with carbon dioxide-based expanders and discuss the risks and benefits associated with this new technology. At their site, the authors have enrolled 34 patients using 36 experimental devices in total, and have found significantly shorter expansion and overall reconstruction times in the patient-controlled tissue expander group. The authors believe that carbon dioxide-based devices may play a significant role in the future of implant-based breast reconstruction, and may be widely applicable to other areas of plastic surgery that also involve tissue expansion.


Invasive techniques utilized in chronic pain management.
A multidisciplinary approach to the treatment of chronic pain has been one of the most effective means of restoring the ability of a patient to return to an increased level of function. Many techniques used for diagnostic and therapeutic means have been utilized as part of this approach. This paper will describe some of the more common invasive techniques used in the treatment of chronic pain.


Hepatic uptake of protein-bound ligands: effect of an unstirred Disse space.
Uptake of protein-bound substances by the liver was modeled considering concurrent depletion of unbound ligand (i.e., not bound to protein)along the length of a sinusoid as well as within a 0.5-micron unstirred boundary layer at the surface of the hepatic parenchymal cells. The development completes a previous exploration of Weisiger et al. [Am. J. Physiol. 261 (Gastrointest. Liver Physiol. 24): G872-G884, 1991]. Ligand is carried across the unstirred layer by albumin, producing a deviation from binding equilibrium inside and outside the unstirred layer. The resulting differential equations have a closed solution. In the case of tight binding, the unbound ligand in the sinusoid is in a quasi-steady state, and the unbound fraction becomes constant along the flow path, except for a very short section at its beginning. During hepatic oleate uptake, the unbound oleate concentration rises from 39% of the equilibrium value at 0.1 microM albumin and 0.01 microM oleate to 78% at 0.5 microM albumin and 0.05 microM oleate. diffusion through the unstirred layer and across the cell membrane was found, in the model, to contribute to the overall resistance to oleate uptake in a complementary fashion.


Bacterial contamination of the small intestine is an important cause of occult malabsorption in the elderly.
A study was conducted to examine the contribution that occult malabsorption makes to malnutrition among elderly patients admitted to an acute geriatric ward. Malnutrition was defined by anthropometric, haematological, and biochemical measurements. Out of 490 patients, 55--many of whom had presented with non-gastrointestinal symptoms--were found to be malnourished. In 31 poor diet alone was probably the cause, but in the remaining 24 patients previously unrecognised malabsorption was detected. Of these patients, 17 were found to have bacterial contamination of the small bowel (nine with duodenojejunal diverticula, four after gastric surgery, and four diagnosed as contamination with "no sump"). In 10 patients contamination was confirmed by culture of intestinal juice: Escherichia coli was predominant in nine cases, and anaerobic organisms in one. Small bowel bacterial overgrowth without a "blind loop" or obvious underlying cause has not previously been fully proved in the elderly. Coeliac disease was detected in two patients, and chronic pancreatitis in two. Occult malabsorption is an important cause of malnutrition in the elderly. Such malnutrition not infrequently occurs in geriatric patients presenting to hospital with non-specific symptoms of physical deterioration.


Clinical Outcomes of Prophylactic and Therapeutic Plasmapheresis in Adult Deceased-Donor Kidney Transplant Recipients With Primary Focal Segmental Glomerulosclerosis.
High recurrence and inferior graft survival rates have been reported for kidney transplant recipients with primary focal segmental glomerulosclerosis. Plasmapheresis is widely used to treat posttransplant relapsing focal segmental glomerulosclerosis, but the effectiveness of prophylactic plasmapheresis remains controversial. In this single-center retrospective study, 21 adult deceased-donor kidney transplant recipients who received prophylactic plasmapheresis were analyzed. Of these, 10 received posttransplant prophylactic plasmapheresis only (less-intensive regimen) and 11 received pre- and posttransplant prophylactic plasmapheresis (more-intensive regimen). Patients with recurrence were treated with steroids and plasmapheresis. Median follow-up was 45 months (interquartile range, 30-107 mo). At last visit, 20/21 patients (95%) were alive and 17/21 (81%) had functioning grafts. Cumulative focal segmental glomerulosclerosis recurrence rate was 38% (8/21): 30% (3/10) in the less-intensive and 45% (5/11) in the more-intensive group (P = .6594). Four of 8 patients (50%) with relapse eventually had graft loss due to recurrence: 100% (3/3) in the less-intensive and 20% (1/5) in the more-intensive group (P = .1429). Complete remission was observed in 25% (2/8) of recipients with recurrence: 0% (0/3) in the less-intensive and 40% (2/5) in the more-intensive group (P = .4643). Two of 8 patients (25%) remained plasmapheresis dependant: 0% (0/3) in the less-intensive and 40% (2/5) in the more-intensive group (P = .4643). Response rate (complete/partial) was higher in the more-intensive group (80% [4/5] vs 0% [0/3]; P = .1429); however, overall, the 2 regimens did not show significantly different outcomes. Comparison between this series and a historical control group of 52 patients with primary focal segmental glomerulosclerosis transplanted at our center and not receiving plasmapheresis prophylaxis did not demonstrate any advantages. No benefits from prophylactic plasmapheresis in deceased-donor kidney transplant recipients with primary focal segmental glomerulosclerosis were shown. Prospective randomized studies comparing alternative preemptive strategies are warranted.


On drug treatment and social control: Russian narcology's great leap backwards.
The medical discipline of narcology in Russia is a subspecialty of psychiatry from the Soviet era and it is given warrant to define the scope of health activities with regard to alcohol and other drug use, drug users, and related problems. Narcological practice is in turn constrained by the State. The emergence of widespread injection opiate use and associated HIV morbidities and mortalities during the first decade following the collapse of the Soviet Union has brought the contradictions in Russian narcological discourse into high relief. Narcology officials in the Russian Federation have consistently opposed substitution treatment for opiate dependence--the replacement of a short-acting illegal substance with a longer acting prescribed drug with similar pharmacological action but lower degree of risk. Thus, despite the addition of methadone and buprenorphine to WHO's list of essential medicines in 2005 and multiple position papers by international experts calling for substitution treatment as a critical element in the response to HIV (IOM, 2006; UNODC, UNAIDS, and WHO, 2005), methadone or buprenorphine remain prohibited by law in Russia. The authors detail Russian opposition to the prescription of methadone and buprenorphine, describing four phenomena: (1) the dominance of law enforcement and drug control policy over public health and medical ethics; (2) the conflation of Soviet era alcoholism treatment with treatment for opiate dependence; (3) the near universal representation of detoxification from drugs as treatment for dependence; and (4) a framework for judging treatment efficacy that is restricted to "cure" versus "failure to cure," and does not admit its poor outcomes or recognize alternative frameworks for gauging treatment of opiate dependence. In keeping with this position, Russian narcology officials have taken an implacable ideological stance toward illicit drug use, the people who use drugs, and their treatment. By adopting policies and practices totally unsupported by scientific evidence and inquiry, officials in Russia have rendered narcology (and medical practice) insensitive to the alarming rates and continued spread of HIV, with its dire morbidity and mortality rates in the Russian Federation, turning their backs on all the other health problems posed by opiate use and dependence itself.


Population variability under stressors is dependent on body mass growth and asymptotic body size.
The recruitment and biomass of a fish stock are influenced by their environmental conditions and anthropogenic pressures such as fishing. The variability in the environment often translates into fluctuations in recruitment, which then propagate throughout the stock biomass. In order to manage fish stocks sustainably, it is necessary to understand their dynamics. Here, we systematically explore the dynamics and sensitivity of fish stock recruitment and biomass to environmental noise. Using an age-structured and trait-based model, we explore random noise (white noise) and autocorrelated noise (red noise) in combination with low to high levels of harvesting. We determine the vital rates of stocks covering a wide range of possible body mass (size) growth rates and asymptotic size parameter combinations. Our study indicates that the variability of stock recruitment and biomass are probably correlated with the stock's asymptotic size and growth rate. We find that fast-growing and large-sized fish stocks are likely to be less vulnerable to disturbances than slow-growing and small-sized fish stocks. We show how the natural variability in fish stocks is amplified by fishing, not just for one stock but for a broad range of fish life histories.


Decanoyl lysophosphatidic acid induces platelet aggregation through an extracellular action. Evidence against a second messenger role for lysophosphatidic acid.
Platelets rapidly convert 1,2-didecanoyl-sn-glycerol into its corresponding phosphatidic acid and lysophosphatidic acid derivatives, thereby providing a means of introducing these two compounds into platelets. 1-Decanoyl-2-lyso-3-sn-phosphatidic acid, when added directly to platelets, induced platelet aggregation and raised intracellular Ca2+ levels at concentrations of 0.3 microM upwards, but was without effect when formed intracellularly from 1,2-didecanoylglycerol at an estimated concentration of approx. 47 microM. This indicates that the site of platelet activation by lysophosphatidic acid is extracellular. A concentration of thrombin (0.2 unit/ml), which produced maximal platelet aggregation, caused an estimated intracellular formation of 20 microM-lysophosphatidic acid in the presence of 2 mM-Ca2+; however, there was no detectable release of lysophosphatidic acid into the bathing medium. Lysophosphatidic acid, therefore, may not be an intracellular second messenger involved in platelet aggregation by thrombin.


Stokes Parameters for 1665-Megacycles-per-second Emission from OH near Source W3.
The Stokes parameters were measured as a function of frequency for the anonmalous 1665-megacycles-per-second OH emission originating near the thermal radio source W3. The emission is highly polarized, and the polarization parameters vary rapidly with frequency. The observed polarization can be described in terms of narrow, roughly Gaussian, emission features, all with uniform polarization but with several features overlapping without coherence near the center of the spectrum. Most of the individual features may be 100-percent polarized. Detailed examination of the brightest features suggest that they are not exactly Gaussian in shape.


[Electroneurography in the carpal tunnel syndrome--selective antidromic sensory and orthodromic measurement of the median nerve in the wrist-palm segment with surface electrodes].
In addition to standard electroneurographic parameters of the median nerve the antidromic sensory and orthodromic conduction velocity in the wrist-palm segment were recorded with surface electrodes. Statistics with stepwise discriminant analysis were based on the data of 102 hands from normal persons and 54 hands from patients with carpal tunnel syndrome. The most sensitive parameter in diagnosis of the mild carpal tunnel syndrome is the antidromic sensory conduction velocity in the wrist-palm segment.


The 9S RNA precursor of Escherichia coli 5S RNA has three structural domains: implications for processing.
The secondary structure of the 9S RNA precursor to ribosomal 5S RNA in Escherichia coli has been determined using chemical reagents and ribonucleases in combination with a reverse transcription procedure. The 9S RNA precursor was generated in vitro by T7 RNA polymerase, and the rrnB operon terminator, T1, was able to terminate the in vitro transcript. The secondary structure model exhibits three structural domains corresponding to a 5' region, a mature region and a terminator region. The mature domain is structurally identical to 5S RNA, and the ribosomal proteins L18 and L25 are able to bind to the precursor. The processing endoribonuclease RNase E cleaves between the structural domains. Moreover, an intramolecular refolding of the nascent transcript must take place if the current view of RNase III processing stems is correct.


Comparative Brucella abortus antibody prevalence in cattle under contrasting husbandry practices in Uganda.
A study was conducted in the Luwero and Nakasongola districts in central Uganda to determine and compare the prevalence and distribution of antibodies against Brucella abortus in cattle under contrasting husbandry practices, using two serological tests. Three hundred and fifteen serum samples were systematically sampled from 29 farms and subsequently tested using the Rose Bengal plate test (RBPT) and Indirect Antibody Enzyme Linked Immunosorbent Assay (I-ELISA). The overall prevalence of antibodies against Brucella abortus in the Nakasongola and Luwero districts was 2.4% and 4.7% on RBPT, compared with 1.2% and 3.34 % on I-ELISA. There was no significant difference between the results obtained by RBPT and indirect antibody ELISA (p > 0.05). It was noted that antibodies against Brucella abortus were widely spread over different farms regardless of the cattle grazing system (p > 0.05). Based on the findings, it is feasible to use RBPT as a cheaper screening alternative for brucellosis. A comprehensive national brucellosis study should be undertaken to study the epidemiology and prevalence of brucellosis in Uganda.


Adherence of group A streptococci to pharyngeal cells: a role in the pathogenesis of rheumatic fever.
We used an assay in vitro to investigate the possible role of streptococcal adherence to human pharyngeal cells in the pathogenesis of acute rheumatic fever. There was no difference in adherence of rheumatic fever-associated and non-associated strains of group A streptococci to pooled pharyngeal cells of normal people. Likewise, streptococci not associated with rheumatic fever adhered equally well to cells taken from normal people and from patients with rheumatic heart disease. However, the pharyngeal cells of all nine rheumatic heart disease patients tested had increased avidity for adherence for a rheumatic fever-associated strain of streptococcus compared to the pharyngeal cells obtained from age- and sex-matched controls. Increased streptococcal adherence to pharyngeal cells of rheumatic fever-prone patients may play a role in the pathogenesis of rheumatic fever.


Parasite worm antigens instruct macrophages to release immunoregulatory extracellular vesicles.
Emerging evidence suggests that immune cells not only communicate with each other through cytokines, chemokines, and cell surface receptors, but also by releasing small membranous structures known as extracellular vesicles (EVs). EVs carry a variety of different molecules that can be taken up by recipient cells. Parasitic worms are well known for their immunomodulatory properties, but whether they can affect immune responses by altering EV-driven communication between host immune cells remains unclear. Here we provide evidence that stimulation of bone marrow-derived macrophages (BMDMs) with soluble products of Trichuris suis (TSPs), leads to the release of EVs with anti-inflammatory properties. Specifically, we found that EVs from TSP-pulsed BMDMs, but not those from unstimulated BMDMs can suppress TNFα and IL-6 release in LPS-stimulated BMDMs and BMDCs. However, no polarization toward M1 or M2 was observed in macrophages exposed to EVs. Moreover, EVs enhanced reactive oxygen species (ROS) production in the exposed BMDMs, which was associated with a deregulated redox homeostasis as revealed by pathway analysis of transcriptomic data. Proteomic analysis identified cytochrome p450 (CYP450) as a potential source of ROS in EVs from TSP-pulsed BMDMs. Finally, pharmacological inhibition of CYP450 activity could suppress ROS production in those BMDMs. In summary, we find that TSPs can modulate immune responses not only via direct interactions but also indirectly by eliciting the release of EVs from BMDMs that exert anti-inflammatory effects on recipient cells.


Artificial neural network (ANN) approach for modeling of Pb(II) adsorption from aqueous solution by Antep pistachio (Pistacia Vera L.) shells.
A three-layer artificial neural network (ANN) model was developed to predict the efficiency of Pb(II) ions removal from aqueous solution by Antep pistachio (Pistacia Vera L.) shells based on 66 experimental sets obtained in a laboratory batch study. The effect of operational parameters such as adsorbent dosage, initial concentration of Pb(II) ions, initial pH, operating temperature, and contact time were studied to optimise the conditions for maximum removal of Pb(II) ions. On the basis of batch test results, optimal operating conditions were determined to be an initial pH of 5.5, an adsorbent dosage of 1.0 g, an initial Pb(II) concentration of 30 ppm, and a temperature of 30 degrees C. Experimental results showed that a contact time of 45 min was generally sufficient to achieve equilibrium. After backpropagation (BP) training combined with principal component analysis (PCA), the ANN model was able to predict adsorption efficiency with a tangent sigmoid transfer function (tansig) at hidden layer with 11 neurons and a linear transfer function (purelin) at output layer. The Levenberg-Marquardt algorithm (LMA) was found as the best of 11 BP algorithms with a minimum mean squared error (MSE) of 0.000227875. The linear regression between the network outputs and the corresponding targets were proven to be satisfactory with a correlation coefficient of about 0.936 for five model variables used in this study.


Impact of missing values on the ability of the acute physiology and chronic health evaluation III and Japan risk of death models to predict mortality.
This study assessed model performance of the Acute Physiology and Chronic Health Evaluation (APACHE) III and Japan Risk of Death (JROD) when degraded by the number and category of missing variables. We also examined the impact of missing data on predicted mortality for facilities with missing physiological variables. We obtained data from the Japanese Intensive care PAtient Database (JIPAD). We calculated observed and predicted mortality rates using the APACHE III and JROD and the standardized mortality ratio (SMR) by the number and category of missing variables. Smoothed spline curves were calculated for the SMR to the missing proportion of the facility. A total of 61,357 patients from 57 ICUs were included between April 2015 and March 2019. The APACHE III and JROD SMRs increased as the number of missing values increased. The SMR in the APACHE III model was elevated in facilities with a larger proportion of missing in each of the APS categories, arterial blood gas, albumin, glucose, and bilirubin. Facilities with a high proportion of missing albumin data preserved their SMRs in only the JROD model. An increased number of missing physiological variables resulted in falsely low predicted mortality rates and high SMRs.


HTD: Heterogeneous Task Decoupling for Two-Stage Object Detection.
Decoupling the sibling head has recently shown great potential in relieving the inherent task-misalignment problem in two-stage object detectors. However, existing works design similar structures for the classification and regression, ignoring task-specific characteristics and feature demands. Besides, the shared knowledge that may benefit the two branches is neglected, leading to potential excessive decoupling and semantic inconsistency. To address these two issues, we propose Heterogeneous task decoupling (HTD) framework for object detection, which utilizes a Progressive Graph (PGraph) module and a Border-aware Adaptation (BA) module for task-decoupling. Specifically, we first devise a Semantic Feature Aggregation (SFA) module to aggregate global semantics with image-level supervision, serving as the shared knowledge for the task-decoupled framework. Then, the PGraph module performs progressive graph reasoning, including local spatial aggregation and global semantic interaction, to enhance semantic representations of region proposals for classification. The proposed BA module integrates multi-level features adaptively, focusing on the low-level border activation to obtain representations with spatial and border perception for regression. Finally, we utilize the aggregated knowledge from SFA to keep the instance-level semantic consistency (ISC) of decoupled frameworks. Extensive experiments demonstrate that HTD outperforms existing detection works by a large margin, and achieves single-model 50.4%AP and 33.2% APs on COCO test-dev set using ResNet-101-DCN backbone, which is the best entry among state-of-the-arts under the same configuration. Our code is available at https://github.com/CityU-AIM-Group/HTD.


Tumours of the adrenal gland and paraganglia.
This classification is arranged in two parts in order to take into account the different origins, structures, and functions of the cortex and medulla. The tabular classification is a simplified version of that suggested for adrenal tumours in man, and includes cortical adenoma and carcinoma, phaeochromocytoma, chemodectoma, neurofibroma, ganglioneuroma and ganglioneuroblastoma, and neuroblastoma. A detailed functional classification is not given, since the hormonal activity of many adrenal tumours in animals is less well known than it is in man. Of the tumour-like lesions listed, cortical hyperplasia is particularly important in several species.


Lyophilized apple counteracts the development of hypercholesterolemia, oxidative stress, and renal dysfunction in obese Zucker rats.
Apples may have selective effects on abnormalities associated with the plurimetabolic syndrome. Therefore, the effects of 20% lyophilized apple supplementation on plasma and tissue lipids and on protection against susceptibility to oxidative stress and renal dysfunction were investigated in Zucker lean (Fa/-) or obese (fa/fa) rats. The experimental diets were equilibrated for sugar supply, contained 0.25 g/100 g cholesterol and provided only one third of the vitamin E requirement. Obese Zucker rats were hypercholesterolemic with cholesterol accumulation in LDL and HDL fractions. The apple diet lowered plasma and LDL cholesterol (-22 and -70%, respectively, P < 0.01) in obese Zucker rats and, in parallel, reduced triglyceride accumulation in heart and liver. Zucker rats fed the apple diet also had a larger intestinal pool and greater fecal excretion of bile acids. The heart concentration and urinary excretion of malondialdehyde were reduced by apple consumption in obese Zucker rats, suggesting better protection against peroxidation. Glucosuria and proteinuria in obese Zucker rats were also suppressed by the apple diet. In conclusion, despite their moderate fiber content, apples improve substantially the lipid status and peroxidative parameters in obese Zucker rats, suggesting that other plant constituents such as polyphenols are involved in these effects.


Effects of NS2B-NS3 protease and furin inhibition on West Nile and Dengue virus replication.
West Nile virus (WNV) and Dengue virus (DENV) replication depends on the viral NS2B-NS3 protease and the host enzyme furin, which emerged as potential drug targets. Modification of our previously described WNV protease inhibitors by basic phenylalanine analogs provided compounds with reduced potency against the WNV and DENV protease. In a second series, their decarboxylated P1-trans-(4-guanidino)cyclohexylamide was replaced by an arginyl-amide moiety. Compound 4-(guanidinomethyl)-phenylacetyl-Lys-Lys-Arg-NH2 inhibits the NS2B-NS3 protease of WNV with an inhibition constant of 0.11 µM. Due to the similarity in substrate specificity, we have also tested the potency of our previously described multibasic furin inhibitors. Their further modification provided chimeric inhibitors with additional potency against the WNV and DENV proteases. A strong inhibition of WNV and DENV replication in cell culture was observed for the specific furin inhibitors, which reduced virus titers up to 10,000-fold. These studies reveal that potent inhibitors of furin can block the replication of DENV and WNV.


pANCA, ASCA, and OmpC antibodies in patients with ankylosing spondylitis without inflammatory bowel disease.
Patients with ankylosing spondylitis (AS) can suffer concurrently from inflammatory bowel disease (IBD), as ulcerative colitis (UC) or Crohn's disease (CD). Serological markers have been described to diagnose IBD. We investigated IBD serological markers in AS patients without IBD and whether these antibodies enable differentiating patients with AS and IBD from those without IBD. Frequencies of perinuclear antineutrophil cytoplasmic antibodies (pANCA), antibodies to the cell-wall mannan of Saccharomyces cerevisiae (ASCA), and antibodies to porin protein C of Escherichia coli (OmpC) were evaluated in 179 patients: 52 with AS, 50 with UC, 51 with CD, and 26 with IBD and AS. Patient groups were matched for age and sex. All AS patients fulfilled the 1984 modified New York criteria. IBD was ascertained by clinical, endoscopic, and microscopic findings. In 55% of the AS patients without manifest IBD at least one antibody associated with IBD was observed. pANCA, ASCA (IgA and/or IgG), and OmpC antibodies were found in 21%, 30%, and 19% of the AS patients, respectively. pANCA was more frequently present in AS with concurrent UC than in AS alone (OR 8.2, 95% CI 1.2-55.6), thus being an indicator for UC in AS patients. Antibodies associated with IBD are detectable in more than half of AS patients without symptoms or signs of IBD. A relatively recent marker in this setting, OmpC antibodies, does not contribute to the differentiation between AS and type of IBD. Presence of pANCA, however, is significantly increased in AS patients who also have UC, and is an indicator to perform endoscopy. These results corroborate a pathophysiological link between AS and IBD.


A New Hybrid Spatio-Temporal Model For Estimating Daily Multi-Year PM2.5 Concentrations Across Northeastern USA Using High Resolution Aerosol Optical Depth Data.
The use of satellite-based aerosol optical depth (AOD) to estimate fine particulate matter (PM2.5) for epidemiology studies has increased substantially over the past few years. These recent studies often report moderate predictive power, which can generate downward bias in effect estimates. In addition, AOD measurements have only moderate spatial resolution, and have substantial missing data. We make use of recent advances in MODIS satellite data processing algorithms (Multi-Angle Implementation of Atmospheric Correction (MAIAC), which allow us to use 1 km (versus currently available 10 km) resolution AOD data. We developed and cross validated models to predict daily PM2.5 at a 1×1km resolution across the northeastern USA (New England, New York and New Jersey) for the years 2003-2011, allowing us to better differentiate daily and long term exposure between urban, suburban, and rural areas. Additionally, we developed an approach that allows us to generate daily high-resolution 200 m localized predictions representing deviations from the area 1×1 km grid predictions. We used mixed models regressing PM2.5 measurements against day-specific random intercepts, and fixed and random AOD and temperature slopes. We then use generalized additive mixed models with spatial smoothing to generate grid cell predictions when AOD was missing. Finally, to get 200 m localized predictions, we regressed the residuals from the final model for each monitor against the local spatial and temporal variables at each monitoring site. Our model performance was excellent (mean out-of-sample R2=0.88). The spatial and temporal components of the out-of-sample results also presented very good fits to the withheld data (R2=0.87, R2=0.87). In addition, our results revealed very little bias in the predicted concentrations (Slope of predictions versus withheld observations = 0.99). Our daily model results show high predictive accuracy at high spatial resolutions and will be useful in reconstructing exposure histories for epidemiological studies across this region.


Design, synthesis, and pharmacological properties of new heteroarylpyridine/heteroarylpyrimidine derivatives as CB(2) cannabinoid receptor partial agonists.
Recent developments indicate that CB(2) receptor ligands have the potential to become therapeutically important. To explore this potential, it is necessary to develop compounds with high affinity for the CB(2) receptor. Very recently, we have identified the oxazinoquinoline carboxamides as a novel class of CB(2) receptor full agonists. In this paper we describe the medicinal chemistry of a new series of heteroaryl-4-oxopyridine/7-oxopyrimidine derivatives. Some of the reported compounds showed high affinity and potency at the CB(2) receptor while showing only modest affinity for the centrally expressed CB(1) cannabinoid receptor. Moreover, we found that the functionality of these ligands is controlled by the nature of the heteroaryl function condensed with the pyridine ring. In 3,5-cyclic adenosine monophosphate (cAMP) assays, the novel series show dose-dependent effects on the modulation of forskolin-induced cAMP production, revealing different behaviors as full agonists, partial agonists, and inverse agonists.


Leg Fidgeting Improves Executive Function following Prolonged Sitting with a Typical Western Meal: A Randomized, Controlled Cross-Over Trial.
Prolonged uninterrupted sitting and a typical Western meal, high in fat and refined sugar, can additively impair cognitive and cerebrovascular functions. However, it is unknown whether interrupting these behaviours, with a simple desk-based activity, can attenuate the impairment. The aim of this study was to determine whether regular leg fidgeting can off-set the detrimental effects of prolonged sitting following the consumption of a typical Western meal, on executive and cerebrovascular function. Using a randomized cross-over design, 13 healthy males consumed a Western meal and completed 180-min of prolonged sitting with leg fidgeting of 1 min on/4 min off (intervention [INT]) and without (control [CON]). Cognitive function was assessed pre and post sitting using the Trail Maker Test (TMT) parts A and B. Common carotid artery (CCA) blood flow, as an index of brain flow, was measured pre and post, and cerebral (FP1) perfusion was measured continuously. For TMT B the CON trial significantly increased (worsened) completion time (mean difference [MD] = 5.2 s, d = 0.38), the number of errors (MD = 3.33, d = 0.68) and cognitive fatigue (MD = 0.73, d = 0.92). Compared to CON, the INT trial significantly improved completion time (MD = 2.3 s, d = 0.97), and prevented declines in cognitive fatigue and a reduction in the number of errors. No significant changes in cerebral perfusion or CCA blood flow were found. Leg fidgeting for 1-min on/4-min off following a meal high in fats and refined sugars attenuated the impairment in executive function. This attenuation in executive function may not be caused by alterations in CCA blood flow or cerebral perfusion.


Human sinus node responses to repetitive, ramped carotid baroreceptor stimuli.
When arterial pressure rises spontaneously, baroreceptor areas are presented with repetitive stimuli of progressively increasing intensities. We simulated rising arterial pressure in 18 healthy young adults by applying trains of repetitive, ramped, R-wave-coupled neck suction, and we related P-P interval responses to intensities of stimuli with least-squares linear regression. We found that the P-P interval response to the stimulus train we used is immediate and highly linear (most correlation coefficients were above 0.90). In studies in which the base-line heart rate was less than 75 beats/min, cardiac inhibition was maximal in the cardiac cycle in which the stimulus was delivered. Decay of inhibition commences rapidly after the end of baroreceptor stimulation and proceeds with time constants that are independent of maximum levels of inhibition. P-P interval shortening (cardioacceleration) comprises an integral feature of baroreflex responses, such that inhibitory stimuli set in motion oscillations of heart period above and below base-line levels. Our data suggest that the pattern of sinus node responses during transitions of arterial pressure results from a complex interplay among several factors, including baroreflex responsiveness, base-line heart rate, the rate decay of baroreflex inhibition, and the biphasic nature of sinus node responses to inhibitory cholinergic interventions.


Muscle function during fatigue in myoadenylate deaminase-deficient Dutch subjects.
Myoadenylate deaminase (MAD) is an enzyme active in skeletal muscle, probably during exercise of moderate intensity but certainly during vigorous exercise, when the deamination of AMP leads to increased levels of IMP and ammonia. There is controversy about the clinical significance of MAD deficiency. The main objective of the present study was to investigate the extent to which genetically confirmed MAD deficiency affects muscle function under conditions of maximal short-term electrically induced activation. The left hand was immobilized and adductor pollicis muscle function was investigated. To exclude the influence of central factors, such as the patient's motivation, the ulnar nerve was maximally electrically activated and force output was measured at the thumb. Sixty rapid shortening contractions resulted in a decrease of maximal power to 34.2+/-5.4% and 33.3+/-6.3% (means+/-S.D.) of the values for unfatigued muscle in the control and MAD-deficient subjects respectively (P>0.05; n=7). Maximal isometric forces and shortening velocities did not differ between groups in unfatigued, fatigued or recovered muscle. None of the subjects experienced exercise-related muscle aches or cramps. In conclusion, MAD deficiency does not appear to affect adductor pollicis muscle force, shortening velocity and relaxation, either during or after maximal short-term activation.


Analysis of intracellularly recorded phasic bursting by mammalian neuroendocrine cells.
Phasic bursting by magnocellular neuroendocrine cells (MNCs) in the mammalian supraoptic and paraventricular nuclei (SON and PVN) consists of successive periods of action potentials and inactivity. It has previously been correlated with increased release of vasopressin from the neurohypophysis. In the present studies we investigated the neuronal mechanisms underlying this firing pattern. Using coronal slices of rat hypothalamus, we recorded intracellularly from neurons that are considered to be MNCs, based on several criteria. Eight of the 29 cells in this study displayed phasic burst patterns similar to those previously recorded extracellularly from MNCs in intact animals. Among the eight phasic cells, low levels of steady current injection could dramatically alter burst periodicity. Steady hyperpolarization revealed patterned synaptic input in only one case; in the remainder of the cells, nonsynaptic mechanisms appeared to account for periodic bursting. The phasic burst pattern usually appeared to be spike dependent, each burst arising from one or several depolarizing after-potentials (DAPs). Summed DAPs formed a plateau potential, which provided a depolarizing drive for further spiking. Spike frequency decreased late in the burst, and then the plateau potential terminated. During the quiescent period, burst excitability appeared to increase coincident with a small slow depolarization. Spikes and their summating DAPs could then initiate another burst. In several silent MNCs, a brief supra-threshold current pulse could initiate a prolonged afterdischarge, which had the properties of a phasic burst. Two MNCs that fired with a fast-continuous pattern were tested with brief hyperpolarizing current pulses; after each pulse, spike activity ceased and a plateau potential was revealed. Therefore, it appears that a maintained plateau potential (summed DAPs) can drive fast-continuous firing. In one case a periodic bombardment of excitatory postsynaptic potentials (EPSPs) generated a phasic firing pattern. The dependence of the burst characteristics on membrane potential, the apparent lack of patterned synaptic input in most cells, and the ability to evoke bursts with brief stimuli support the hypothesis that bursting in some MNCs involves an endogenous mechanism. Furthermore, phasic firing may be driven by tonic excitatory input. The data on phasic, silent, and fast-continuous cells suggest that many MNCs can generate DAPs and plateau potentials.


Age at natural menopause in Beirut, Lebanon: the role of reproductive and lifestyle factors.
To determine the median age of natural menopause and factors associated with the timing of menopause in Beirut, Lebanon. RESEARCH DESGIN: A population-based sample of 298 women were interviewed using a semi-structured questionnaire. Logit analysis and logistic regression were used to estimate the median age and identify correlates of menopausal status. The median age of natural menopause in Beirut, Lebanon is estimated to be 49.3 years. Not being currently married (odds ratio (OR)=4.19, 95% CI: 1.53, 11.51) and smoking (OR = 1.02 for each year of smoking, 95% CI: 1.00, 1.05) are significantly associated with an earlier age at menopause. Women with menstrual bleeding longer than 5 days have later ages at menopause (OR = 0.50, 95% CI: 0.26, 0.97). Age at menarche, parity, education and socio-economic status are not statistically associated with the age at menopause. The age at natural menopause in Lebanon is comparable to median ages reported for women in industrialized countries (49.3-51.4). Our results emphasize the role of smoking in determining an earlier age at menopause and indicate that reproductive characteristics affect the timing of menopause.


Dysregulated Immunity to Clostridioides difficile in IBD Patients Without a History of Recognized Infection.
Clostridioides difficile is a toxin-secreting bacteria that is an urgent antimicrobial resistance threat, with approximately 25% of patients developing recurrent infections. Inflammatory bowel disease (IBD) patients are at increased risk of severe, recurrent C. difficile infection. To investigate a role for C. difficile infection in IBD pathogenesis, we collected peripheral blood and stool from 20 each of ulcerative colitis patients, Crohn's disease patients, and healthy control subjects. We used a flow cytometric activation induced marker assay to quantify C. difficile toxin-specific CD4+ T cells and 16S ribosomal RNA sequencing to study microbiome diversity. We found IBD patients had significantly increased levels of C. difficile toxin B-specific CD4+ T cells, but not immunoglobulin G or immunoglobulin A, compared with healthy control subjects. Within antigen-specific CD4+ T cells, T helper type 17 cells and cells expressing the gut homing receptor integrin β7 were reduced compared with healthy control subjects, similar to our previous study of non-IBD patients with recurrent C. difficile infection. Stool microbiome analysis revealed that gut homing, toxin-specific CD4+ T cells negatively associated with microbial diversity and, along with T helper type 17 cells, positively associated with bacteria enriched in healthy control subjects. These data suggest that IBD patients, potentially due to underlying intestinal dysbiosis, experience undiagnosed C. difficile infections that result in impaired toxin-specific immunity. This may contribute to the development of inflammatory T cell responses toward commensal bacteria and provide a rationale for C. difficile testing in IBD patients.


Infrahyoid myofascial flap transfer for the prevention of concave deformity and gustatory sweating after parotidectomy.
Concave deformities and gustatory sweating are the most common complications that cause substantial patient dissatisfaction after parotidectomy. Various surgical methods to prevent these complications have been described. However, effective techniques have not been established, especially in patients with medium- to large-sized parotidectomy defects. We evaluated the utility of infrahyoid myofascial flap reconstruction of parotidectomy defects for the prevention of these complications. We conducted a retrospective case series study in patients with a benign or malignant parotid tumor measuring over 4 cm who underwent immediate pedicle infrahyoid myofascial flap reconstruction after total or subtotal parotidectomy or total resection of either the superficial or deep parotid gland at our hospital. Subjective analyses of facial symmetry, postoperative concave deformities of the anterior neck, gustatory sweating, voice disorders, odynophagia, neck scarring in the parotid and anterior neck areas, sensory disorders, pain, and neck stiffness were performed using patient interview data. Objective evaluations of facial symmetry were made by the first or second author. Both analyses were performed after a follow-up of more than six months. Additionally, patient demographic data, clinicopathological factors, parotidectomy and skin incision types, flap survival, and postoperative complications were evaluated. We included eight patients (male, n=5; mean age, 69.3 years [range, 37-93 years]). Procedures included total or subtotal parotidectomy (n=4), superficial lobe parotidectomy (n=2), and deep lobe parotidectomy with partial superficial lobe parotidectomy (n=2). Infrahyoid myofascial flaps reached the cranial tip of the parotid defect without tension, and their volume sufficiently filled the parotidectomy defect in all patients. There were no local signs of insufficient blood flow within the transferred flaps. Objective and subjective assessments were made after a mean duration of 1.2 years (range, 0.6-1.8). Postoperatively, no patient subjectively reported facial asymmetry. Objectively, facial symmetry was "good" in four patients and "fair" in four patients. No distinctly visible concave deformity in the parotid or anterior neck area occurred in any patient. Gustatory sweating occurred in one patient; this individual had the largest parotidectomy defect. Only one patient experienced donor site morbidity (mild anterior neck stiffness) related to infrahyoid myofascial flap elevation. Although complete prevention of gustatory sweating was unsuccessful, infrahyoid myofascial flap reconstruction of medium- to large-sized parotidectomy defects led to postoperative facial symmetry with minimal donor site morbidity.


Spatial dynamics of carbon storage: a case study from Turkey.
Forest ecosystems have an important role in carbon cycle at both regional and global scales as an important carbon sink. Forest degradation and land cover changes, caused by deforestation and conversion to non-forest area, have a strong impact on carbon storage. The carbon storage of forest biomass and its changes over time in the Hartlap planning unit of the southeastern part of Turkey have been estimated using the biomass expansion factor method based on field measurements of forests plots with forest inventory data between 1991 and 2002. The amount of carbon storage associated with land use and land cover changes were also analyzed. The results showed that the total forested area of the Hartlap planning unit slightly increased by 2.1%, from 27,978.7 ha to 28,282.6 ha during the 11-year period, and carbon storage increased by 9.6%, from 390,367.6 to 427,826.9 tons. Carbon storage of conifer and mixed forests accounted for about 70.6% of carbon storage in 1991, and 67.8% in 2002 which increased by 14,274.6 tons. Land use change and increasing forest area have a strong influence on increasing biomass and carbon storage.


Gene expression signature for detection of gastric cancer in peripheral blood.
Gastric cancer (stomach cancer) is the fifth most common malignancy and the third leading cause of cancer-associated mortality worldwide. Identifying gastric cancer patients at an early and curable stage of the disease is essential if mortality rates for this disease are to decrease. A non-invasive blood-based test that is an indicator of gastric cancer risk would likely be of benefit in identifying gastric cancer patients at an early stage, and such a test may enhance clinical decision making. This study identified a four-gene expression signature in peripheral blood samples associated with gastric cancer. A total of 216 blood samples were collected, including those from 36 gastric cancer patients, 55 healthy controls and 125 patients with other carcinomas, and gene expression profiles were examined using an Affymetrix Gene Profiling microarray. Blood gene expression profiles were compared between patients with stomach cancer, healthy controls and patients affected with other malignancies. A four-gene panel was identified comprising purine-rich element binding protein B, structural maintenance of chromosomes 1A, DENN/MADD domain containing 1B and programmed cell death 4. The four-gene panel discriminated gastric cancer with an area under the receiver-operating-characteristic curve of 0.99, an accuracy of 95%, sensitivity of 92% and specificity of 96%. The non-invasive nature of the blood test, together with the relatively high accuracy of the four-gene panel may assist physicians in gastric cancer screening decision making.


Skin pentosidine and telomere length do not covary with age in a long-lived seabird.
The questions about why and how senescence occurs in the wild are among the most pertinent ones in evolutionary ecology. Telomere length is a commonly used marker for aging, while other biomarkers of aging have received considerably less attention. Here we studied how another potent indicator of aging-skin pentosidine concentration-relates to age and blood telomere length in a long-lived seabird with well-documented reproductive senescence. We found no associations between telomere length, skin pentosidine and chronological age in male common gulls (Larus canus), aging from 2 to 30 years. However, the variance in telomere length was 4.6 times higher among the birds older than 13 years, which hints at relaxed selection on telomere length among the birds that have passed their prime age of reproduction. These results suggest that physiological and chronological ages may be largely uncoupled in our study system. Furthermore, our findings do not support a hypothesis about the presence of a common physiological factor (e.g., such as oxidative stress) that would cause covariation between two independent markers of aging.


Floc stability and adhesion of green-fluorescent-protein-marked bacteria to flocs in activated sludge.
Wastewater is often treated using the activated sludge process. Flocculation and subsequent sedimentation of flocs are vital steps in this process that have direct influence on the quality of the effluent water from wastewater treatment plants. Since cells that remain free-living will decrease the quality of the effluent water it is important to understand the mechanisms of bacterial adhesion to flocs. The green fluorescent protein (GFP) was used as a cellular marker to study bacterial adhesion to activated sludge flocs in situ in sludge liquor. Cell surface hydrophobicity (CSH) was shown to be an important factor that determined the relative bacterial adhesion potential. High CSH correlated with high numbers of attached cells. However, the absolute adhesion of two test bacteria to different sludge flocs varied and could not be explained by the floc characteristics. Confocal laser scanning microscopy of GFP-marked cells showed their position in the floc matrix in situ. Hydrophobic cells attached not only on the surface but also within the floc, whereas hydrophilic cells did not. This indicates that cells may penetrate the flocs through channels and pores and increase the effective surface, which in turn makes the clarification of the wastewater effluent more efficient. The addition of polymers is common practice in wastewater treatment and was shown to increase bacterial adhesion to the flocs. A decrease in surface tension caused by addition of DMSO decreased adhesion, indicating the detrimental effect of surfactants on flocculation. An understanding of basic bacterial adhesion and aggregation mechanisms is important for the management and control of biotechnological wastewater treatment.


Maternal tobacco smoking, nicotine replacement and neurobehavioural development.
Abstract The adverse effects of prenatal cigarette smoke exposure on human reproductive outcomes are a major scientific and public health concern. In the United States, approximately 25% of women of childbearing age currently smoke cigarettes, and only a small percentage of these individuals quit after learning of their pregnancy. Women interested in smoking cessation during pregnancy have a number of options, including behavioural and pharmacological aids, but nicotine replacement therapy (NRT) is by far the most common approach. While NRT avoids exposure to the myriad compounds present in tobacco smoke, nicotine itself causes damage to the developing nervous system. The purpose of this article is to review the detrimental effects of developmental tobacco smoke exposure on short- and long-term outcomes with particular emphasis on neurobehavioural consequences. In conclusion based on the clear, adverse effects of nicotine on brain development observed in human and animal studies, we suggest that safer alternatives for smoking cessation in pregnancy are badly needed.


Membrane Wrapping Efficiency of Elastic Nanoparticles during Endocytosis: Size and Shape Matter.
Using coarse-grained molecular dynamics simulations, we systematically investigate the receptor-mediated endocytosis of elastic nanoparticles (NPs) with different sizes, ranging from 25 to 100 nm, and shapes, including sphere-like, oblate-like, and prolate-like. Simulation results provide clear evidence that the membrane wrapping efficiency of NPs during endocytosis is a result of competition between receptor diffusion kinetics and thermodynamic driving force. The receptor diffusion kinetics refer to the kinetics of receptor recruitment that are affected by the contact edge length between the NP and membrane. The thermodynamic driving force represents the amount of required free energy to drive NPs into a cell. Under the volume constraint of elastic NPs, the soft spherical NPs are found to have similar contact edge lengths to rigid ones and to less efficiently be fully wrapped due to their elastic deformation. Moreover, the difference in wrapping efficiency between soft and rigid spherical NPs increases with their sizes, due to the increment of their elastic energy change. Furthermore, because of its prominent large contact edge length, the oblate ellipsoid is found to be the least sensitive geometry to the variation in NP's elasticity among the spherical, prolate, and oblate shapes during the membrane wrapping. In addition, simulation results indicate that conflicting experimental observations on the efficiency of cellular uptake of elastic NPs could be caused by their different mechanical properties. Our simulations provide a detailed mechanistic understanding about the influence of NPs' size, shape, and elasticity on their membrane wrapping efficiency, which serves as a rational guidance for the design of NP-based drug carriers.


Renal Effects of Intensive Volume Removal in Heart Failure Patients With Preexisting Worsening Renal Function.
Background The relationship between intensive volume removal in acute decompensated heart failure patients with preexisting worsening renal function (WRF) and renal tubular injury, postdischarge renal function, and clinical outcomes is unknown. Methods and Results We used data from the multicenter CARRESS-HF trial (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) that randomized patients with acute decompensated heart failure and preexisting WRF to intensive volume removal with stepped pharmacological therapy or fixed rate ultrafiltration. Patients in the urinary renal tubular injury biomarker substudy (NAG [N-acetyl-b-D-glucosaminidase], KIM-1 [kidney injury molecule-1], and NGAL [neutrophil gelatinase-associated lipocalin]) were evaluated (N=105). The severity of prerandomization WRF was unrelated to baseline renal tubular injury biomarkers ( r=0.14; P=0.17). During randomized intensive volume removal, creatinine further worsened in 53% of patients. Despite a small to moderate magnitude increase in creatinine in most of these patients, postrandomization WRF was strongly associated with worsening in renal tubular injury biomarkers (odds ratio, 12.6; P=0.004). This observation did not differ by mode of volume removal (stepped pharmacological therapy versus ultrafiltration, Pinteraction=0.46). Increase in renal tubular injury biomarkers was associated with a higher incidence of hemoconcentration (odds ratio, 3.1; P=0.015), and paradoxically, better recovery of creatinine at 60 days ( P=0.01). Conclusions In acute decompensated heart failure patients with preexisting WRF, intensive volume removal resulted in a further worsening of creatinine approximately half of the time, a finding associated with a rise in tubular injury biomarkers. However, decongestion and renal function recovery at 60 days were superior in patients with increased tubular injury markers. These data suggest that the benefits of decongestion may outweigh any modest or transient increases in serum creatinine or tubular injury markers that occur during intensive volume removal. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00608491.


Epidermal Growth Factor Receptor (EGFR) Mutations and Anaplastic Lymphoma Kinase/Oncogene or C-Ros Oncogene 1 (ALK/ROS1) Fusions Inflict Non-Small Cell Lung Cancer (NSCLC) Female Patients Older Than 60 Years of Age.
BACKGROUND Lung cancer has become a leading disease for the tumor-induced mortality. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancers. The present research aimed to evaluate the correlation between the anaplastic lymphoma kinase/oncogene or c-ros oncogene 1 (ALK/ROS1) fusions or mutations of epidermal growth factor receptor (EGFR) and ages or gender of patients. MATERIAL AND METHODS Among 1449 NSCLC patients, 457 patients who were diagnosed as consecutive EGFR mutations or ALK/ROS1 fusions between November 2016 and February 2018 were involved in the present study. EGFR genes or ALK/ROS1 mutations were detected by using DNA sequencing technique and amplification-refractory mutation system (ARMS). The mRNAs of ROS1 and ALK fusion were examined by using polymerase chain reaction technique and fusion gene detection kit. RESULTS Females were more often inflicted by the EGFR mutations, especially for the exon 19 deletion and L858R mutation. There were significantly more ALK/ROS1 fusions in females compared to males (P<0.05) and significantly more ALK/ROS1 fusions in <60 years of age patients compared to patients older than 60 years of age (P<0.05). Exon 21 L858R and L861Q dominantly occurred in patients ≥60 years of age and exon 19 deletion in patients <60 years of age. EML-ALK-1 mainly existed in the female NSCLC patients. CONCLUSIONS EGFR mutations and ALK/ROS1 fusions mainly occurred in the NSCLC female patients who were older than 60 years of age.


Photoinduced Direct Electron Transfer between Quinoxalin-2(1H)-ones and Alkyl Carboxylic Acids for C-H Alkylation.
The progress of efficient and sustainable approaches for decarboxylative coupling reactions is synthetically appealing due to the structural diversity, lack of toxicity, and widespread commercial accessibility of carboxylic acids. However, the decarboxylation reaction still encounters challenges related to the utilization of oxidants, catalysts, and prefunctionalization conditions. We report herein a mild method that facilitates direct electron transfer between alkyl carboxylic acids and excited-state substrates for C-H alkylation of quinoxalin-2(1H)-ones without the involvement of any catalyst or additive.


"Ts and Blues" in pregnancy.
Data on the prenatal and postnatal effects of Talwin and Pyribenzamine ("Ts and Blues") abuse in pregnancy were compared with those from a control group. Anemia, syphilis, hepatitis and gonorrhea were more common in mothers abusing Ts and Blues. Their infants were more often growth retarded. Neonatal withdrawal was seen in 35%.


Scholarly Activity During Pediatric Fellowship.
The educational requirements for pediatric fellows include at least 12 months of scholarly activity and generation of a work product. Yet there lacks detailed guidance on how programs can best integrate scholarly activity training into fellowships. Our objectives were to understand the resources and barriers to training and identify factors associated with productivity. We surveyed pediatric fellowship program directors (FPDs) nationally in 2019. Data analysis included descriptive statistics, χ2 and Fisher's exact tests, and multivariable modeling to identify factors associated with high productivity (>75% of fellows in the past 5 years had an article from their fellowship accepted). A total of 499 of 770 FPDs responded (65%). A total of 174 programs (35%) were highly productive. The most frequent major barriers were a lack of funding for fellows to conduct scholarship (21%, n = 105) and lack of sufficient divisional faculty mentorship (16%, n = 79). The median number of months for scholarship with reduced clinical obligations scholarship was 17. A total of 40% (n = 202) of FPDs believed training should be shortened to 2 years for clinically oriented fellows. Programs with a T32 and a FPD with >5 publications in the past 3 years were twice as likely to be productive. Not endorsing lack of adequate Scholarship Oversight Committee expertise and a research curriculum as barriers was associated with increased productivity (odds ratio = 1.83-1.65). Despite significant protected fellow research time, most fellows do not publish. Ensuring a program culture of research may provide the support needed to take projects to publication. The fellowship community may consider reevaluating the fellowship duration, particularly for those pursing nonresearch focused careers.


Brain Emboli After Left Ventricular Endocardial Ablation.
Catheter ablation for ventricular tachycardia and premature ventricular complexes (PVCs) is common. Catheter ablation of atrial fibrillation is associated with a risk of cerebral emboli attributed to cardioversions and numerous ablation lesions in the low-flow left atrium, but cerebral embolic risk in ventricular ablation has not been evaluated. We enrolled 18 consecutive patients meeting study criteria scheduled for ventricular tachycardia or PVC ablation over a 9-month period. Patients undergoing left ventricular (LV) ablation were compared with a control group of those undergoing right ventricular ablation only. Patients were excluded if they had implantable cardioverter defibrillators or permanent pacemakers. Radiofrequency energy was used for ablation in all cases and heparin was administered with goal-activated clotting times of 300 to 400 seconds for all LV procedures. Pre- and postprocedural brain MRI was performed on each patient within a week of the ablation procedure. Embolic infarcts were defined as new foci of reduced diffusion and high signal intensity on fluid-attenuated inversion recovery brain MRI within a vascular distribution. The mean age was 58 years, half of the patients were men, half had a history of hypertension, and the majority had no known vascular disease or heart failure. LV ablation was performed in 12 patients (ventricular tachycardia, n=2; PVC, n=10) and right ventricular ablation was performed exclusively in 6 patients (ventricular tachycardia, n=1; PVC, n=5). Seven patients (58%) undergoing LV ablation experienced a total of 16 cerebral emboli, in comparison with zero patients undergoing right ventricular ablation (P=0.04). Seven of 11 patients (63%) undergoing a retrograde approach to the LV developed at least 1 new brain lesion. More than half of patients undergoing routine LV ablation procedures (predominately PVC ablations) experienced new brain emboli after the procedure. Future research is critical to understanding the long-term consequences of these lesions and to determining optimal strategies to avoid them.


[Organochlorine compounds: blood levels in mothers, newborns, and infants, in maternal milk and formula. Study in the province of Huelva].
We have studied the presence of organochlorine compounds (OCC), DDT, HCB, HCH and isomers alpha, beta and gamma or lindane, hepta-chloro-epoxide (HE) and polychlorobiphenyl compounds (PCB), in 50 mothers and their newborn babies. The samples studied included the umbilical cord blood, blood from the mothers during the delivery, blood from the baby at one and three months of age, and the milk fed to the babies at these periods (breast n = 30; bottle n = 20). The objectives of the study were: 1) To detect the levels of OCC in the different samples. 2) To discover the difference in levels between breast and bottle fed babies. 3) To quantify the variations of the levels in the different samples. 4) To check whether the acceptable daily intake (ADI) established for these OCC is exceeded among these babies. The analyses were done in the National Institute of Toxicology in Seville, by using the following methods, gas chromatography, electron capture detector and mass spectrometry. The statistical analysis was based on the Kruskal-Wallis, Shapiro-Wilks, Levene, Pooled and Separate tests. We have found significant levels of OCC in the samples analyzed. The PCBs are the compounds in our study which have the highest levels, indeed being one of the highest levels documented to date. We verify the decline in OCC of agricultural origin in relation to previous reports in our country, as has also been reflected in the international literature in recent years. The levels of OCC in breast fed babies are significantly higher than those in bottle fed babies.


Addressing Knowledge Gaps in the 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: a Review of Recent Coronary Artery Calcium Literature.
Coronary artery calcium (CAC) has been proposed as an integrator of information from traditionally measured, non-traditionally measured, and unmeasured risk factors for coronary atherosclerosis. The 2013 American College of Cardiology/American Heart Association Guideline on the Assessment of Cardiovascular Risk identified several knowledge gaps regarding CAC, including radiation risks, cost-effectiveness, and improving discrimination and reclassification of estimated risk over the Pooled Cohort Equations in the ACC/AHA Atherosclerotic Cardiovascular Disease Estimator. In this review, we focus on recent CAC literature addressing these knowledge gaps. We further highlight the potential for CAC to enrich future randomized controlled trials. The use of CAC allows for personalization of cardiovascular risk despite the presence or absence of traditional risk factors across many demographics. Avenues to reduce radiation exposure associated with CAC scanning include increasing the interval between scans for those with CAC scores of zero and estimating CAC from non-cardiac gated CT scans. While limited studies have suggested cost-effectiveness in cardiac risk assessment with the incorporation of CAC in screening algorithms, several studies have demonstrated the ability of CAC to identify non-traditional risk factors that may be used to expand cardiovascular risk personalization in other high-risk populations. Literature from the past 2 years further supports CAC as a strong marker to personalize cardiac risk assessment. While multiple potential avenues to reduce radiation are available and cost-effectiveness analyses are encouraging, further studies are necessary to clarify patient selection for CAC scanning given the interplay between CAC and other imaging modalities in risk personalization algorithms.


The burden of non-infectious intraocular inflammatory eye diseases: a systematic literature review.
Non-infectious inflammatory eye diseases (IEDs), although rare, are complex and varied and may result in detrimental effects. A systematic literature review was conducted on the clinical outcome and economic burden of IED. The Ovid search platform (Wolters Kluwer) was used to access scientific literature databases, including MEDLINE, Embase, Cochrane libraries, Health Technology Assessment and the NHS Economic Evaluation database. The search strategy targeted clinical and economic outcomes research in 2009-2016. Titles and abstracts resulting from inclusion criteria were screened, and two reviewers independently extracted relevant information from the selected full-text articles. Thirty-nine papers met the inclusion criteria - 21 clinical trials, 7 database analyses, 6 non-systematic literature reviews with expert commentary, 3 chart reviews, and 2 surveys - which assessed steroids, immunosuppressants, implants and biologics. Patients experienced considerable morbidity, much of which was associated with corticosteroid use. The average annual healthcare costs of patients with IED were $13,728 to $32,268 in 2009 US dollars, which amounted to 3.1 to 8.3 times that of patients without IED. Steroid-releasing intraocular implants were associated with higher up-front costs, close monitoring requirements, potential for implant removal and increased rates of adverse ocular events than systemic steroids. IEDs are rare and complex conditions that threaten eyesight and impose considerable morbidity as well as a substantial economic burden. This review confirms that further research is needed to more fully explore the burden of IED and treatment-related adverse events, as well as appropriate means for clinicians to intensify treatment.


Detection of Viruses in Clinical Samples by Use of Metagenomic Sequencing and Targeted Sequence Capture.
Metagenomic shotgun sequencing (MSS) is a revolutionary approach to viral diagnostic testing that allows simultaneous detection of a broad range of viruses, detailed taxonomic assignment, and detection of mutations associated with antiviral drug resistance. To enhance sensitivity for virus detection, we previously developed ViroCap, a targeted sequence capture panel designed to enrich nucleic acid from a comprehensive set of eukaryotic viruses prior to sequencing. To demonstrate the utility of MSS with targeted sequence capture for detecting clinically important viruses and characterizing clinically important viral features, we used ViroCap to analyze clinical samples from a diagnostic virology laboratory containing a broad range of medically relevant viruses. From 26 samples, MSS with ViroCap detected all of the expected viruses and 30 additional viruses. Comparing sequencing after capture enrichment with standard MSS, we detected 13 viruses only with capture enrichment and observed a consistent increase in the number and percentage of viral sequence reads as well as the breadth and depth of coverage of the viral genomes. Compared with clinical testing, MSS enhanced taxonomic assignment for 15 viruses, and codons associated with antiviral drug resistance in influenza A virus, herpes simplex virus (HSV), human immunodeficiency virus (HIV), and hepatitis C virus (HCV) could be analyzed. Overall, in clinical samples, MSS with targeted sequence capture provides enhanced virus detection and information of clinical and epidemiologic relevance compared with clinical testing and MSS without targeted sequence capture.


Designs for the evaluation of the endotoxin assay as a diagnostic test.
The comprehensive evaluation of the usefulness of a new diagnostic test should include a hierarchy of assessments ranging from reliability and validity to impact on clinical decision making and outcome. This paper reviews some of the design methodology appropriate for evaluation of an endotoxin assay such as the Limulus Amebocyte Lysate test. Primary focus is on the design and analysis of studies aimed at establishing diagnostic validity. However, suggestions are made for the design of clinical studies of management change and to determine the impact on patient outcome. Results from such studies must be combined into a cost-utility calculation eventually to determine societal benefit.


The benefits of child-parent psychotherapy to marital satisfaction.
Given the interdependent nature of relationships within the family system, the purpose of this study was to examine the potential role of child-parent psychotherapy (CPP) to extend its positive influence beyond the mother-child relationship within families challenged by maternal depression. Accordingly, we analyzed longitudinal associations between depressive symptoms and marital satisfaction over 3 years in order to evaluate if the benefits of CPP to mother-child attachment security might generalize within the family and indirectly benefit marital relationships. We tested our hypotheses in a randomized control trial of CPP (N = 159 families) to examine the intervention's efficacy in families with mothers with histories of depression since the target child's birth (Mage = 20.4 months, SD = 2.5; 56% boys). Using hierarchical linear modeling (HLM) with an actor-partner interdependence modeling (APIM) framework, the results supported our hypothesis as well as revealed significant associations between depressive symptoms and marital functioning. Specifically, shifts in mothers' depressive symptoms within specific waves of follow-up were associated with corresponding shifts in both their husbands' and their own relationship satisfaction in those same waves. After controlling for those effects, only mothers with a history of depression who received CPP demonstrated slight improvements in relationship satisfaction over the 3 years of the study, suggesting secondary benefits of CPP within the family system. Results are discussed in terms of the importance of examining therapeutic processes within the larger family system. Concerning future research, we also suggest examining potential mechanisms through which CPP might influence marital satisfaction. (PsycINFO Database Record


Molecular characterization and expression in Escherichia coli of three beta-1,3-glucanase genes from Lysobacter enzymogenes strain N4-7.
Lysobacter enzymogenes strain N4-7 produces multiple biochemically distinct extracellular beta-1,3-glucanase activities. The gluA, gluB, and gluC genes, encoding enzymes with beta-1,3-glucanase activity, were identified by a reverse-genetics approach following internal amino acid sequence determination of beta-1,3-glucanase-active proteins partially purified from culture filtrates of strain N4-7. Analysis of gluA and gluC gene products indicates that they are members of family 16 glycoside hydrolases that have significant sequence identity to each other throughout the catalytic domain but that differ structurally by the presence of a family 6 carbohydrate-binding domain within the gluC product. Analysis of the gluB gene product indicates that it is a member of family 64 glycoside hydrolases. Expression of each gene in Escherichia coli resulted in the production of proteins with beta-1,3-glucanase activity. Biochemical analyses of the recombinant enzymes indicate that GluA and GluC exhibit maximal activity at pH 4.5 and 45 degrees C and that GluB is most active between pH 4.5 and 5.0 at 41 degrees C. Activity of recombinant proteins against various beta-1,3 glucan substrates indicates that GluA and GluC are most active against linear beta-1,3 glucans, while GluB is most active against the insoluble beta-1,3 glucan substrate zymosan A. These data suggest that the contribution of beta-1,3-glucanases to the biocontrol activity of L. enzymogenes may be due to complementary activities of these enzymes in the hydrolysis of beta-1,3 glucans from fungal cell walls.


Comparison of intraocular pressure fluctuations before and after ab interno trabeculectomy in pseudoexfoliation glaucoma patients.
Ab interno trabeculectomy (AIT) with the Trabectome has been shown to reduce intraocular pressure (IOP) in eyes with pseudoexfoliation (PEX) glaucoma. Here, we examined the change of IOP fluctuations before and after only AIT or AIT with cataract surgery in PEX patients using the contact lens sensor Triggerfish®. This was a prospective open-label study. Twenty-four consecutive patients with PEX glaucoma were included. Twelve patients underwent cataract surgery and AIT (triple-surgery group), and 12 patients underwent only AIT (single-surgery group). In each eye, IOP fluctuations over 24 h were measured with the contact lens sensor before and at 3 months after the surgery. We compared the change of IOP fluctuation before and after operation. We also evaluated the difference in IOP changes between the triple- and single-surgery groups. At 3 months after the surgeries, the mean IOP was significantly reduced from 23.5±6.5 mmHg to 14.6±2.8 mmHg in the single-surgery group and from 22.5±3.0 mmHg to 11.5±2.9 mmHg in the triple-surgery group. The mean IOP reduction rate was significantly higher in the triple-surgery group compared to the single-surgery group (p=0.0358). In both groups, the mean range of IOP fluctuations was significantly decreased during nocturnal periods. The mean range of 24 h IOP fluctuations was decreased in the triple-surgery group (p=0.00425), not in the single-surgery group (p=0.970). Triple surgery could decrease IOP value and the IOP fluctuations to a greater extent than single surgery in PEX glaucoma patients.


Pulmonary toxicity of instilled silver nanoparticles: influence of size, coating and rat strain.
Particle size and surface chemistry are potential determinants of silver nanoparticle (AgNP) respiratory toxicity that may also depend on the lung inflammatory state. We compared the effects of intratracheally-administered AgNPs (20 nm and 110 nm; polyvinylpyrrolidone (PVP) and citrate-capped; 0.1 mg/Kg) in Brown-Norway (BN) and Sprague-Dawley (SD) rats. In BN rats, there was both a neutrophilic and eosinophilic response, while in SD rats, there was a neutrophilic response at day 1, greatest for the 20 nm citrate-capped AgNPs. Eosinophilic cationic protein was increased in bronchoalveolar lavage (BAL) in BN and SD rats on day 1. BAL protein and malondialdehyde levels were increased in BN rats at 1 and 7 days, and BAL KC, CCL11 and IL-13 levels at day 1, with increased expression of CCL11 in lung tissue. Pulmonary resistance increased and compliance decreased at day 1, with persistence at day 7. The 20 nm, but not the 110 nm, AgNPs increased bronchial hyperresponsiveness on day 1, which continued at day 7 for the citrate-capped AgNPs only. The 20 nm versus the 110 nm size were more proinflammatory in terms of neutrophil influx, but there was little difference between the citrate-capped versus the PVP-capped AgNPs. AgNPs can induce pulmonary eosinophilic and neutrophilic inflammation with bronchial hyperresponsiveness, features characteristic of asthma.


A comparative study of the surface structure, acidity, and catalytic performance of tungstated zirconia prepared from crystalline zirconia or amorphous zirconium oxyhydroxide.
Tungstated zirconias prepared from W deposition on zirconium oxyhydroxide are reportedly active for alkane isomerization, whereas solids synthesized by impregnation of zirconia are inactive. The origin of the differences between the two preparations is not fully understood. The present paper examines the influence of W surface density and the nature of the support on the surface structure, development of the acidity, and catalytic performance of WO(x)()/ ZrO(2) catalysts. Two series of catalysts containing W surface densities up to 5.2 at. W/nm(2) were prepared by pore volume impregnation of two different supports: zirconium oxyhydroxide and predominantly tetragonal zirconia (65% tetragonal, 35% monoclinic). The texture and structure of the catalysts were investigated by BET measurements, X-ray diffraction, Raman and infrared spectroscopy. The catalytic activity was tested for 2-propanol dehydration and n-hexane isomerization. For catalysts obtained by impregnation of Zr oxyhydroxide, Raman results showed that W was present as a surface phase. Infrared spectra indicated an increase in the degree of polymerization of W species with increasing W surface density. The development of the acidity was monitored by lutidine adsorption and desorption at 523 K, followed by infrared spectroscopy. The results indicated the presence of a threshold of W surface density at 1.3 at. W/ nm(2) for the detection of these acid sites, followed by a progressive increase in their abundance with increasing W surface density. The development of Brønsted acidity correlated with the evolution of the infrared bands attributed to "extensively" polymerized W species. A direct relationship was observed between the abundance of Brønsted acid sites and the catalytic activity for 2-propanol dehydration. For n-hexane isomerization, compared to 2-propanol dehydration, a higher threshold of W surface densities (3.4 at. W/ nm(2)) for the development of activity was observed. The difference was attributed to stronger Brønsted acid sites required for n-hexane isomerization. The catalysts prepared by impregnation of zirconia exhibited comparable behavior. For a given W surface density, the crystalline composition of the support (tetragonal/monoclinic zirconia), the W surface structure, abundance of Brønsted acid sites, and catalytic performance were similar. Thus, in an apparent variance with some of the results reported in the literature with respect to the influence of preparation methods, no significant effect of the initial form of the support (Zr oxyhydroxide versus predominantly tetragonal zirconia) was evidenced.


A PILOT PROJECT IN TRAINING FOR MENTAL HEALTH LIBRARIANSHIP.
In an effort to recruit and train competent personnel for its medical library, Central Louisiana State Hospital undertook a pilot project in preprofessional training in mental health librarianship. Students received an introduction to the library as it operates in the hospital setting through a survey of the mental health sciences and the needs for library resources and services with special emphasis upon the librarian as a member of the hospital team.


Overview of mitral regurgitation in Europe: results from the European Registry of mitral regurgitation (EuMiClip).
To determine the prevalence of mitral regurgitation (MR) in a large cohort of consecutive patients undergoing clinically indicated echocardiography and to examine the distribution of primary and secondary MR. All patients undergoing an echocardiographic study in 19 European centres within a 3-month period were prospectively included. MR assessment was performed as recommended by the European Association of Cardiovascular Imaging (EACVI). MR was classified according to mechanism as primary or secondary and aetiologies were reported. A total of 63 463 consecutive echocardiographic studies were reviewed. Any degree of MR was described in 15 501 patients. Concomitant valve disease of at least moderate grade was present in 28.5% of patients, being tricuspid regurgitation the most prevalent. In the subgroup of moderate and severe MR (n = 3309), 55% of patients had primary MR and 30% secondary MR. Both mechanisms were described in 14% of the studies. According to Carpentier's classification, 26.7% of MR were classified as I, 19.9% of MR as II, 22.4% of MR as IIIa, and 31.1% of MR as IIIb. To date, this is the largest echocardiography-based study to analyse the prevalence and aetiology distribution of MR in Europe. The burden of secondary MR was higher than previously described, representing 30% of patients with significant MR. In our environment, degenerative disease is the most common aetiology of primary MR (60%), whereas ischaemic is the most common aetiology of secondary MR (51%). Up to 70% of patients with severe primary MR may have a Class I indication for surgery. However, the optimal therapeutic approach for secondary MR remains uncertain.


Early rearing interacts with temperament and housing to influence the risk for motor stereotypy in rhesus monkeys (Macaca mulatta).
Laboratory and zoo housed non-human primates sometimes exhibit abnormal behaviors that are thought to reflect reduced wellbeing. Previous research attempted to identify risk factors to aid in the prevention and treatment of these behaviors, and focused on demographic (e.g. sex or age) and experience-related (e.g. single housing or nursery rearing) factors. However, not all animals that display abnormal behavior possess these risk factors and some individuals that possess a risk factor do not show behavioral abnormalities. We hypothesized that other aspects of early experience and individual characteristics might identify animals that were more likely to display one specific abnormal behavior, motor stereotypy (MS). Using logistic regression we explored the influence of early rearing (involving four different types of rearing conditions), and variation in temperament, on likelihood of displaying MS while controlling for previously identified risk factors. Analyses indicated that having a greater proportion of life lived indoors, a greater proportion of life-indoors singly-housed, and a greater number of anesthesias and blood draws significantly increased the risk of displaying MS (P < 0.001). Rearing condition failed to independently predict the display of MS; however significant interactions indicated that single housing had a greater impact on risk for indoor-reared animals versus outdoor-reared animals, and for indoor mother-reared animals versus nursery-reared animals. There were no main effects of temperament, although interactions with rearing were evident: scoring high on Gentle or Nervous was a risk factor for indoor-reared animals but not outdoor-reared animals. The final model accounted for approximately 69.3 % of the variance in the display of MS, and correctly classified 90.6% of animals. These results indicate that previously identified risk factors may impact animals differently depending on the individual's early rearing condition. These results are also the first in non-human primates to demonstrate that individual difference factors, like temperament, could be additional tools to identify animals at highest risk for motor stereotypy.


Appropriateness Criteria for Neuroimaging of Adult Headache Patients in the Emergency Department: How Are We Doing?
The American College of Radiology (ACR) developed Appropriateness Criteria (ACR-AC) for diagnostic imaging to reduce overuse and promote high-yield, cost-effective, evidence-based decision-making. For adult headaches, there are 16 variants with specific imaging recommendations. Headache accounts for 4.5% of emergency department (ED) visits, and 61% are chronic. Imaging for headaches has increased in the past 2 decades, with intracranial pathology diagnoses going down. Evidence suggests that there is poor knowledge of the ACR-AC among advanced practice nurses (APNs) and nonradiologist physicians. The ACR-AC recommendations were examined using the Health Care Cost and Utilization Project State Emergency Department Data (HCUP SEDD) from Maryland in 2013. Imaging proportions were examined, as well as differences between residency program hospitals and hospitals that have APNs in the ED. Of the 11,109 chronic headache visits, a quarter underwent computed tomography ([CT]; 26.9%) and 3.6% underwent magnetic resonance imaging (MRI); the ACR-AC does not recommend use of either of these in patients with chronic headache. There were significant practice differences related to hospital teaching and whether APNs were employed in the ED or not. For patients with posttraumatic headache, there were no significant differences in practice. Computed tomography was used in 76.4% of posttraumatic headache visits. It is unknown whether the ACR-AC are being used in the ED, and there is variability in following the recommendations. Posttraumatic headache protocol is well established in the ED, but chronic headache continues to be a problem in imaging overuse despite recommendations. Radiological education, including the ACR-AC, as well as radiation dosing and exposure information should be part of APN, physician, and registered nurse education, as well as continuing education. Continuing education is critical for adherence to the ACR-AC, as the recommendations are complex and continuously evolving. In addition, to minimize overuse of CT in headaches, the ACR-AC should be integrated into clinical decision support to promote best imaging practices.


Visit preferences of middle-aged vs older critically ill patients.
To differentiate between middle-aged and older adults' visiting preferences in critical care settings. Patients' preferences for visiting, perceptions of illness severity and extent of fatigue associated with visiting and an objective measurement of illness severity while in critical care were surveyed within 3 days after transfer from the critical care unit. Interviews occurred on the transitional care units with patients who transferred from either the coronary care or surgical intensive care units in a large Northeast teaching hospital. Fifty-three middle-aged (35 through 65 years) and 46 older (over 65 years) patients were surveyed (N = 99). Both middle-aged and older patients consistently wanted to limit the number of visitors to two or three persons per visit. Compared with middle-aged patients, a greater proportion of older patients preferred to limit visits to once a day and wanted the visit length to be unlimited. A greater proportion of older coronary care unit patients preferred to limit visits to two times a day than older surgical unit patients. Middle-aged and older patients differed in their preferences for visits, with sufficient variation in responses to warrant tailoring visits to the unique preferences of patients based on age and clinical setting.


Radiomics in head and neck cancer: from exploration to application.
In the context of clinical oncology, a fundamental goal of radiomics is the extraction of large amounts of quantitative features whose subsequent analysis can be used for decision support towards personalized and actionable cancer care. Head and neck cancers present a unique set of diagnostic and therapeutic challenges by nature of its complex anatomy and heterogeneity. Radiomics holds the potential to address these barriers, but only if as a collective field we direct future effort towards investigating specific oncologic function and oncologic outcomes, with external validation and collaborative multi-institutional efforts to begin standardizing and refining radiomic signatures. Here we present an overview of radiomic texture analysis methods as well as the software infrastructure, review the developments of radiomics in head and neck cancer applications, discuss unmet challenges, and propose key recommendations for moving the field forward.


Risk factors for cross-country horse falls at one-day events and at two-/three-day events.
The cross-country phase of eventing competitions has been associated with injuries and fatalities to horses and riders. A case-control study was carried out to identify variables that were associated with increased or decreased risk of a horse fall on the cross-country phase at event competitions. After initial analysis, the dataset was split according to the categories of one-day events as compared to two- or three-day events to establish whether significant risk factors varied between the different types of eventing competitions. Data were collected for 121 cases (horse falls) at one-day events, 59 cases at two- or three-day events and for their 540 matched controls. The data were analysed using conditional logistic regression. The variables of no previous refusals on the course, fences with a landing in water and the combined variable of the angle and the spread of the fence were significantly associated with the risk of a horse fall in both datasets. Additional risk factors for one-day event falls were: fences requiring a take-off from water, a drop landing, the rider's knowledge of their position before the cross-country phase and if the rider received cross-country tuition. Three-day event risk factors in the multivariable model included: the camber of the fence and participation in non-equestrian sports by the rider. This study identified variables that were significantly associated with an increase or a decrease in the risk of a horse fall during the cross-country phase of different types of eventing competitions. Some of these variables are modifiable and the results of this study have been reported to the governing body of the sport of eventing in the UK so that possible interventions might be considered.


Cellular localization of protein arginine methyltransferase-5 correlates with grade of lung tumors.
Protein arginine methyltransferase-5 (PRMT5) is a chromatin-modifying enzyme capable of methylating histone and non-histone proteins, and is involved in a wide range of cellular processes that range from transcriptional regulation to organelle biosynthesis. As such, its overexpression has been linked to tumor suppressor gene silencing, enhanced tumor cell growth and survival. Quantitative real-time polymerase chain reaction, Western immunoblot and immunohistochemistry were used to characterize PRMT5 expression in lung cancer cell lines and human tumors. Clinicopathological findings of tissue microarray based samples from 229 patients with non-small cell lung carcinomas (NSCLC) and 133 cases with pulmonary neuroendocrine tumors (NET) were analyzed with regard to nuclear and cytoplasmic PRMT5 expression. There was statistically significant difference in PRMT5 messenger RNA expression between tumors and nonneoplastic lung tissues. Immunoblot experiments showed abundant expression of PRMT5 and its symmetric methylation mark H4R3 in lung carcinoma but not in non-neoplastic human pulmonary alveolar and bronchial epithelial cell lines. More than two thirds of lung tumors expressed PRMT5. High levels of cytoplasmic PRMT5 were detected in 20.5% of NSCLC and in 16.5% of NET; high levels of nuclear PRMT5 were detected in 38.0% of NSCLC and 24.0% of NET. Cytoplasmic PRMT5 was associated with high grade in both NSCLC and pulmonary NET while nuclear PRMT5 was more frequent in carcinoid tumors (p < 0.05). The observed findings support the role of PRMT5 in lung tumorigenesis and reflect its functional dichotomy in cellular compartments. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1611895162102528.


Ectomycorrhizal symbiosis can enhance plant nutrition through improved access to discrete organic nutrient patches of high resource quality.
It is known that roots can respond to patches of fertility; however, root proliferation is often too slow to exploit resources fully, and organic nutrient patches may be broken down and leached, immobilized or chemically fixed before they are invaded by the root system. The ability of fungal hyphae to exploit resource patches is far greater than that of roots due to their innate physiological and morphological plasticity, which allows comprehensive exploration and rapid colonization of resource patches in soils. The fungal symbionts of ectomycorrhizal plants excrete significant quantities of enzymes such as chitinases, phosphatases and proteases. These might allow the organic residue to be tapped directly for nutrients such as N and P. Pot experiments conducted with nutrient-stressed ectomycorrhizal and control willow plants showed that when high quality organic nutrient patches were added, they were colonized rapidly by the ectomycorrhizal mycelium. These established willows (0.5 m tall) were colonized by Hebeloma syrjense P. Karst. for 1 year prior to nutrient patch addition. Within days after patch addition, colour changes in the leaves of the mycorrhizal plants (reflecting improved nutrition) were apparent, and after I month the concentration of N and P in the foliage of mycorrhizal plants was significantly greater than that in non-mycorrhizal plants subject to the same nutrient addition. It seems likely that the mycorrhizal plants were able to compete effectively with the wider soil microbiota and tap directly into the high quality organic resource patch via their extra-radical mycelium. We hypothesize that ectomycorrhizal plants may reclaim some of the N and P invested in seed production by direct recycling from failed seeds in the soil. The rapid exploitation of similar discrete, transient, high-quality nutrient patches may have led to underestimations when determining the nutritional benefits of ectomycorrhizal colonization.