A retrospective study on dioxins and dioxin-like polychlorinated biphenyls in milk and dairy products from the Latium region (Italy) over a 7-year study period (2011-2017).
This study reports the data of polychlorinated dibenzo-p-dioxins (PCDDs), -furans (PCDFs), and polychlorinated biphenyls dioxin-like (dl PCBs) measured in a total of 260 samples of the dairy supply chain collected over a period of 7 years (2011-2017) in the Latium region (Italy). Levels and average profiles of congeners were reported for each group of the analyzed dairy matrices, and any differences between different sampling strategies were considered (around likely pollutant sources or casual sampling). Of the samples, 95.4% resulted compliant with the regulated levels; only samples belonging to the "sheep bulk milk" matrix were found to be above either the action levels or the maximum levels (tot. 12 samples). Raw milk of the sheep species showed the highest averages (PCDD/F 0.248 and dl PCB 0.966 WHO TEQ pg/g of fat) compared to the milk of other species. The buffalo milk showed a content of dl PCB significantly lower (dl PCB: 0.371 WHO TEQ pg/g of fat) than the sheep milk (p<0.05). Dioxins were found to be superior to furans in almost all dairy products, except in the noncompliant samples where furans were higher. The OCDD was found to be the most abundant congener in almost all dairy products. This study provides a first list of reference values for background contamination of the dairy supply chain in the Latium region. These pre-existing values will be useful in all cases of environmental pollution to identify critical situations.


Specialized primary care medical home: A positive impact on continuity of care among autistic adults.
There is a nationally recognized need for innovative healthcare delivery models to improve care continuity for autistic adults as they age out of pediatric and into adult healthcare systems. One possible model of care delivery is called the "medical home". The medical home is not a residential home, but a system where a patient's healthcare is coordinated through a primary care physician to ensure necessary care is received when and where the patient needs it. We compared the continuity of care among autistic adult patients at a specialized primary care medical home designed to remove barriers to care for autistic adults, called the CAST, to matched national samples of autistic adults with private insurance or Medicare. Continuity of primary care among CAST patients was significantly better than that of matched national samples of autistic adult Medicare beneficiaries and similar to that of privately insured autistic adults. Our findings suggest that medical homes, like CAST, are a promising solution to improve healthcare delivery for the growing population of autistic adults.


Risk factors associated with extended-spectrum β-lactamase-producing Enterobacteriaceae carriage at admission in an infant cohort at a tertiary teaching hospital in France.
We describe risk factors associated with extended-spectrum β-lactamase-producing Enterobacteriaceae fecal carriage at admission in an infant population. 12.6% were carrying extended-spectrum β-lactamase-producing Enterobacteriaceae. Klebsiella pneumoniae, and Escherichia coli were the most frequently identified species. Prior antibiotic therapy (P = .016; odds ratio, 4.07; 95% confidence interval: 1.29-12.81) and the presence tracheostomy or gastrostomy (P = .018; odds ratio, 3.62; 95% confidence interval: 1.24-10.53) were independently associated with carriage at admission.


Plasmodium chabaudi antigens synthesized in an mRNA-dependent cell-free translation system.
Intact RNAs were isolated from Plasmodium chabaudi growing synchronously in mice at different stages of the erythrocytic cycle. Translation of the mRNAs using rabbit reticulocyte lysate showed stage-specific patterns comparable to those observed in vivo. Many antigens of P. chabaudi are produced by translation in the rabbit reticulocyte lysate. Some other antigens are predominantly synthesized at a particular stage, indicating that the mRNA populations differ from one stage to another.


Dietary Intake Patterns Are Consistent Across Seasons in a Cohort of Healthy Adults in a Metropolitan Population.
Current literature provides conflicting data regarding seasonal variability in dietary intake. Our aim was to examine seasonal variation in dietary intake in healthy adults from the metropolitan Washington, DC, area. This study utilized an observational cohort design. Male and female healthy volunteers (n=103) between the ages of 18 and 75 years were recruited from the metropolitan Washington, DC, area to participate in a clinical study at the National Institutes of Health Clinical Center from February 2011 to June 2014. Three- to seven-day food records were collected from subjects (n=76) at three time points (12 to 15 weeks apart). Subjects were excluded from analysis (n=27) if they completed less than three time points. Food records were reviewed by nutrition staff, assigned to a season, and coded in Nutrient Data System for Research for energy, macronutrient, micronutrient, and food-group serving analysis. Multivariate general linear models were run on energy, macronutrient, micronutrient, and food-group intakes, while being adjusted for age, sex, race, and body mass index (calculated as kg/m(2)). Subjects had a mean±standard deviation body mass index of 25±3.9 and age of 34±12.4 years. Subject demographics were 71.1% white, 9.2% black/African American, 13.2% Asian, and 6.6% unknown race, with 44.7% males and 55.3% females. Mean intake of energy across seasons was 2,214.6±623.4 kcal with 17.3%±4.1%, 33.6%±5.5%, 46.6%±8.0%, and 2.7%±3.2% of calories from protein, fat, carbohydrate, and alcohol, respectively. Intakes of energy, macronutrients, micronutrients, and food groups did not differ between seasons. People living in the metropolitan Washington, DC, area did not exhibit seasonal variation in dietary intake. Therefore, when designing studies of nutrient intake in a metropolitan population, these findings suggest that investigators do not need to consider the season during which diet is examined.


The prevalence of treatment-emergent central sleep apnea with mandibular advancement device therapy.
Treatment-emergent central sleep apnea (TECSA) describes the appearance or persistence of central sleep apnea while undergoing treatment for obstructive sleep apnea. TECSA is well studied in continuous positive airway pressure therapy with an estimated prevalence of 8%. Based on a few case reports, mandibular advancement devices (MAD) may also provoke TECSA. This study aims to gain insight into the prevalence of TECSA with MAD therapy. This retrospective study includes a total of 129 patients with moderate to severe obstructive sleep apnea who were treated with a custom-made titratable MAD. Baseline and follow-up sleep studies were compared to identify patients with TECSA. Since different diagnostic criteria to define TECSA are used in literature, prevalence was calculated according to three definitions (TECSA-1, -2, and -3). Demographics, MAD treatment variables, and findings of the diagnostic polysomnography were compared between TECSA and non-TECSA patients to identify possible predictors. Depending on the definition used, TECSA was found in 3.1%-7.8% of patients undergoing MAD therapy. TECSA patients had a higher apnea index (9.2 vs 2.0 events/h, P = .042), central apnea-hypopnea index (4.1 vs 0.2 events/h, P = .045) and oxygen desaturation index (23.9 vs 16.3 events/h, P = .018) at baseline compared to non-TECSA patients. No differences were found in demographics and treatment variables. These findings demonstrate that TECSA also occurs in patients starting MAD treatment. Patients with TECSA had a higher apnea index, central apnea-hypopnea index, and oxygen desaturation index at baseline compared to non-TECSA patients. Hellemans S, Van de Perck E, Braem MJ, Verbraecken J, Dieltjens M, Vanderveken OM. The prevalence of treatment-emergent central sleep apnea with mandibular advancement device therapy. J Clin Sleep Med. 2023;19(12):2035-2041.


In-situ X-ray fluorescence to investigate iodide diffusion in opalinus clay: Demonstration of a novel experimental approach.
During the last two decades, the Mont Terri rock laboratory has hosted an extensive experimental research campaign focusing on improving our understanding of radionuclide transport within Opalinus Clay. The latest diffusion experiment, the Diffusion and Retention experiment B (DR-B) has been designed based on an entirely different concept compared to all predecessor experiments. With its novel experimental methodology, which uses in-situ X-ray fluorescence (XRF) to monitor the progress of an iodide plume within the Opalinus Clay, this experiment enables large-scale and long-term data acquisition and provides an alternative method for the validation of previously acquired radionuclide transport parameters. After briefly presenting conventional experimental methodologies used for field diffusion experiments and highlighting their limitations, this paper will focus on the pioneer experimental methodology developed for the DR-B experiment and give a preview of the results it has delivered thus far.


Duration of the protective immune response after prime and booster vaccination of yearlings with a live modified cold-adapted viral vaccine against equine influenza.
We previously created a live vaccine against equine influenza based the new reassortant cold-adapted (Ca) strain A/HK/Otar/6:2/2010. The live vaccine contains surface proteins (HA, NA) from the wild-type virus A/equine/Otar/764/2007 (Н3N8; American Lineage Florida Clade 2), and internal proteins (PB2, PB1, PA, NP, M, NS) from the attenuated Ca donor virus A/Hong Kong/1/68/162/35CA (H3N2). To determine the safety and duration of the protective immune responses, 90 yearlings were intranasally vaccinated in single mode, double mode at an interval of 42 days (10(7.0) EID50/animal for both vaccinations), or with PBS (control group). Ten animals from each group were challenged with the homologous wild-type virus A/equine/Otar/764/07 (Н3N8) at 1, 2, 3, 4, 5, 6, 9 and 12 months after vaccination. Similarly, 10 animals from each group were challenged with the heterologous wild-type virus A/equine/Sydney/2888-8/07 (Н3N8; American Lineage Florida Clade 1) 12 months after vaccination. The vaccine was completely safe, and single intranasal vaccination of yearlings was capable of inducing statistically significant (from P=0.03 to P<0.0001) clinical and virological protection against the homologous virus; however, only double mode vaccination generated significant (from P=0.02 to P<0.0001) protection against the heterologous virus at 12 months (observation period). Interestingly, this vaccine enables the differentiation of infected and vaccinated animals. On this basis of this study, we recommend double intranasal administration of this vaccine at an interval of 42 days in veterinary practice.


Managing patients with dengue fever during an epidemic: the importance of a hydration tent and of a multidisciplinary approach.
Dengue fever is one of the most common tropical diseases worldwide. Early detection of the disease, followed by intravenous fluid therapy in patients with dengue hemorrhagic fever (DHF) or with warning signs of dengue has a major impact on the prognosis. The purpose of this study is to describe the care provided in a hydration tent, including early detection, treatment, and serial follow-up of patients with dengue fever. The analysis included all patients treated in the hydration tent from April 8 to May 9, 2008. The tent was set up inside the premises of the 2nd Military Firemen Group, located in Meier, a neighborhood in Rio de Janeiro, Brazil. The case form data were stored in a computerized database for subsequent assessment. Patients were referred to the tent from primary care units and from secondary city and state hospitals. The routine procedure consisted of an initial screening including vital signs (temperature, blood pressure, heart rate, and respiratory rate), tourniquet test and blood sampling for complete blood count. Over a 31-day period, 3,393 case recordings were seen at the hydration tent. The mean was 109 patients per day. A total of 2,102 initial visits and 1,291 return visits were conducted. Of the patients who returned to the hydration tent for reevaluation, 850 returned once, 230 returned twice, 114 returned three times, and 97 returned four times or more. Overall, 93 (5.3%) patients with DHF seen at the tent were transferred to a tertiary hospital. There were no deaths among these patients. As the epidemics were already widespread and there were no technical conditions for routine serology, all cases of suspected dengue fever were treated as such. Implementing hydration tents decrease the number of dengue fever hospitalizations.


The wonderful and masterful G protein-coupled receptor (GPCR): A focus on signaling mechanisms and the neuroendocrine control of fertility.
Human GnRH deficiency, both clinically and genetically, is a heterogeneous disorder comprising of congenital GnRH deficiency with anosmia (Kallmann syndrome), or with normal olfaction [normosmic idiopathic hypogonadotropic hypogonadism (IHH)], and adult-onset hypogonadotropic hypogonadism. Our understanding of the neural mechanisms underlying GnRH secretion and GnRH signaling continues to increase at a rapid rate and strikingly, the heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) continue to emerge as essential players in these processes. GPCRs were once viewed as binary on-off switches, where in the "on" state they are bound to their Gα protein, but now we understand that view is overly simplistic and does not adequately characterize GPCRs. Instead, GPCRs have emerged as masterful signaling molecules exploiting different physical conformational states of itself to elicit an array of downstream signaling events via their G proteins and the β-arrestins. The "one receptor-multiple signaling conformations" model is likely an evolved strategy that can be used to our advantage as researchers have shown that targeting specific receptor conformations via biased ligands is proving to be a powerful tool in the effective treatment of human diseases. Can biased ligands be used to selectively modulate signaling by GPCR regulators of the neuroendocrine axis in the treatment of IHH? As discussed in this review, the grand possibility exists. However, while we are still very far from developing these treatments, this exciting likelihood can happen through a much greater mechanistic understanding of how GPCRs signal within the cell.


Tumor induced osteomalacia secondary to anaplastic thyroid carcinoma: A case report and review of the literature.
Tumor induced osteomalacia related to anaplastic thyroid cancer has never been reported. We describe a case of tumor induced osteomalacia (TIO) in a patient with a fibroblast growth factor 23 (FGF-23) secreting anaplastic thyroid carcinoma. The current imaging modalities are reviewed. Clinical, biochemical, and radiological assessments were done, including computer tomography (CT) of the neck and skull to thigh positron emission tomography (PET)/CT. The patient underwent surgical tumor debulking three days after presentation due to airway compromise. Molecular studies of the resected tissue were performed using reverse transcriptase-polymerase chain reaction (RT-PCR) and gel electrophoresis for the phosphaturic mesenchymal tumor FGF-23. Resected tissue demonstrated features of anaplastic thyroid cancer with positive markers for FGF-23 protein, consistent with a FGF-23 secreting paraneoplastic tumor. The patient's metastatic burden rapidly progressed as demonstrated by a dramatic rise in serum FGF-23 levels and worsening hypophosphatemia in concert with progression of the metastatic lesions on PET/CT. We believe that our patient's rapidly progressive anaplastic thyroid cancer was responsible for persistent hypophosphatemia and osteomalacia, substantiated by the finding of FGF-23 protein within the thyroid tumor cells. Our case indicates that anaplastic thyroid cancer can cause TIO.


Effects of maintained weight loss on sleep dynamics and neck morphology in severely obese adults.
The goals of the study were to determine if moderate weight loss in severely obese adults resulted in (i) reduction in apnea/hypopnea index (AHI), (ii) improved pharyngeal patency, (iii) reduced total body oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) during sleep, and (iv) improved sleep quality. The main outcome was the change in AHI from before to after weight loss. Fourteen severely obese (BMI > 40 kg/m(2)) patients (3 males, 11 females) completed a highly controlled weight reduction program which included 3 months of weight loss and 3 months of weight maintenance. At baseline and postweight loss, patients underwent pulmonary function testing, polysomnography, and magnetic resonance imaging (MRI) to assess neck morphology. Weight decreased from 134 +/-6.6 kg to 118 +/- 6.1 kg (mean +/- s.e.m.; F = 113.763, P < 0.0001). There was a significant reduction in the AHI between baseline and postweight loss (subject, F = 11.11, P = 0.007). Moreover, patients with worse sleep-disordered breathing (SDB) at baseline had the greatest improvements in AHI (group, F = 9.00, P = 0.005). Reductions in VO(2) (285 +/- 12 to 234 +/-16 ml/min; F = 24.85, P < 0.0001) and VCO(2) (231 +/- 9 to 186 +/- 12 ml/min; F = 27.74, P < 0.0001) were also observed, and pulmonary function testing showed improvements in spirometry parameters. Sleep studies revealed improved minimum oxygen saturation (minSaO(2)) (83.4 +/- 61.9% to 89.1 +/- 1.2%; F = 7.59, P = 0.016), and mean SaO(2) (90.4 +/- 1.1% to 93.8 +/- 1.0%; F = 6.89, P = 0.022), and a significant increase in the number of arousals (8.1 +/- 1.4 at baseline, to 17.1 +/- 3.0 after weight loss; F = 18.13, P = 0.001). In severely obese patients, even moderate weight loss (approximately 10%) boasts substantial benefit in terms of the severity of SDB and sleep dynamics.


Bacterial aneurysm of the intracavernous carotid artery secondary to suppurative otitis media. A case report.
A case of an intracavernous carotid aneurysm, with ophthalmoplegia, secondary to cavernous sinus thrombophlebitis is reported. The necessity of angiography when this condition persists despite adequate antibiotic therapy is stressed.


Objectives to direct the training of emergency medicine residents on off-service rotations: traumatology, Part 3.
This is the thirty-second article in a continuing series of objectives to direct emergency medicine resident experiences on off-service rotations. Instruction during rotations in traumatology may be conducted at the bedside in difficult and demanding clinical settings. Yet, residents must not only obtain an essential fund of knowledge, but also become comfortable with a variety of life-saving and diagnostic procedures. It is essential for residents to have specific goals and objectives to guide their acquisition of knowledge and skills required to manage major trauma effectively.


TADMaster: a comprehensive web-based tool for the analysis of topologically associated domains.
Chromosome conformation capture and its derivatives have provided substantial genetic data for understanding how chromatin self-organizes. These techniques have identified regions of high intrasequence interactions called topologically associated domains (TADs). TADs are structural and functional units that shape chromosomes and influence genomic expression. Many of these domains differ across cell development and can be impacted by diseases. Thus, analysis of the identified domains can provide insight into genome regulation. Hence, there are many approaches to identifying such domains across many cell lines. Despite the availability of multiple tools for TAD detection, TAD callers' speed, flexibility, result inconsistency, and reproducibility remain challenges in this research area. In this work, we developed a computational webserver called TADMaster that provides an analysis suite to directly evaluate the concordance level and robustness of two or more TAD data on any given genome region. The suite provides multiple visual and quantitative metrics to compare the identified domains' number, size, and various comparisons of shared domains, domain boundaries, and domain overlap. TADMaster is an efficient and easy-to-use web application that provides a set of consensus and unique TADs to inform the choice of TADs. It can be accessed at http://tadmaster.io and is also available as a containerized application that can be deployed and run locally on any platform or operating system.


The effect of trimoprostil (trimethyldesoxy prostaglandin E2) on the intrauterine pressure in women.
Prostaglandin E2 is uterotonic. Trimoprostil, a prostaglandin E2 analog, is a gastric antisecretory and cytoprotective agent. The effects of single doses of 0, 0.125, 0.75, and 3.0 mg trimoprostil on intrauterine pressure were measured in a double-blind, crossover study in eight surgically sterile women. The 3 mg dose was not tolerated because of abdominal cramps. The other doses caused a dose-related increase in resting uterine tone and peak pressure with peak effect occurring between 30 and 60 minutes after administration with a duration of about 120 minutes. No effects on the frequency of uterine contractions occurred. Peak mean tone increased from 11.0 to 71.2 mm Hg (p less than 0.01) and peak pressure from 24.6 to 125.1 mm Hg (p less than 0.01) after placebo compared with the 1.5 mg dose. Adverse reactions included abdominal pain that correlated with an increase in intrauterine pressure and tone.


Prediction of N2O emission from local information with Random Forest.
Nitrous oxide is a potent greenhouse gas, with a global warming potential 298 times greater than that of CO2. In agricultural soils, N2O emissions are influenced by a large number of environmental characteristics and crop management techniques that are not systematically reported in experiments. Random Forest (RF) is a machine learning method that can handle missing data and ranks input variables on the basis of their importance. We aimed to predict N2O emission on the basis of local information, to rank environmental and crop management variables according to their influence on N2O emission, and to compare the performances of RF with several regression models. RF outperformed the regression models for predictive purposes, and this approach led to the identification of three important input variables: N fertilization, type of crop, and experiment duration. This method could be used in the future for prediction of N2O emissions from local information.


Sonographic measurement of the volume of the left lateral segment of the liver.
The aim of this study was to evaluate the accuracy of sonography for measuring the volume of the left lateral segment of the liver. The volume of the left lateral segment of the liver was measured with sonography in 101 consecutive patients who were hospitalized between December 1998 and January 2000 for hepatic, biliary, or pancreatic disease or who were donors for a living related liver transplantation. The results were compared with those obtained using CT. The mean calculated volume of the left lateral segment of the liver +/- standard deviation was 261 +/- 118 cm(3) by sonography compared with 274 +/- 123 cm(3) by CT. The relationship between the results of both imaging modalities was linear and statistically significant (r = 0.93; p < 0.0001). Our study demonstrated that sonography has an acceptable level of accuracy and reliability for routine measurement of the volume of the left lateral segment of the liver.


Scaling of resting and maximum hopping metabolic rate throughout the life cycle of the locust Locusta migratoria.
The hemimetabolous migratory locust Locusta migratoria progresses through five instars to the adult, increasing in size from 0.02 to 0.95 g, a 45-fold change. Hopping locomotion occurs at all life stages and is supported by aerobic metabolism and provision of oxygen through the tracheal system. This allometric study investigates the effect of body mass (Mb) on oxygen consumption rate (MO2, μmol h(-1)) to establish resting metabolic rate (MRO2), maximum metabolic rate during hopping (MMO2) and maximum metabolic rate of the hopping muscles (MMO2,hop) in first instar, third instar, fifth instar and adult locusts. Oxygen consumption rates increased throughout development according to the allometric equations MRO2=30.1Mb(0.83±0.02), MMO2=155Mb(1.01±0.02), MMO2,hop=120Mb(1.07±0.02) and, if adults are excluded, MMO2,juv=136Mb(0.97±0.02) and MMO2,juv,hop=103Mb(1.02±0.02). Increasing body mass by 20-45% with attached weights did not increase mass-specific MMO2 significantly at any life stage, although mean mass-specific hopping MO2 was slightly higher (ca. 8%) when juvenile data were pooled. The allometric exponents for all measures of metabolic rate are much greater than 0.75, and therefore do not support West, Brown and Enquist's optimised fractal network model, which predicts that metabolism scales with a 3⁄4-power exponent owing to limitations in the rate at which resources can be transported within the body.


Seeing is believing: the nocturnal malarial mosquito Anopheles coluzzii responds to visual host-cues when odour indicates a host is nearby.
The immediate aim of our study was to analyse the behaviour of the malarial mosquito Anopheles coluzzii (An. gambiae species complex) near a human host with the ultimate aim of contributing to our fundamental understanding of mosquito host-seeking behaviour and the overall aim of identifying behaviours that could be exploited to enhance sampling and control strategies. Based on 3D video recordings of individual host-seeking females in a laboratory wind-tunnel, we found that despite being a nocturnal species, An. coluzzii is highly responsive to a visually conspicuous object, but only in the presence of host-odour. Female mosquitoes approached and abruptly veered away from a dark object, which suggests attraction to visual cues plays a role in bringing mosquitoes to the source of host odour. It is worth noting that the majority of our recorded flight tracks consisted of highly stereotyped 'dipping' sequences near the ground, which have been mentioned in the literature, but never before quantified. Our quantitative analysis of female mosquito flight patterns within ~1.5 m of a host has revealed highly relevant information about responsiveness to visual objects and flight height that could revolutionise the efficacy of sampling traps; the capturing device of a trap should be visually conspicuous and positioned near the ground where the density of host-seeking mosquitoes would be greatest. These characteristics are not universally present in current traps for malarial mosquitoes. The characterisation of a new type of flight pattern that is prevalent in mosquitoes suggests that there is still much that is not fully understood about mosquito flight behaviour.


A novel approach for efficient extrication of overlapping chromosomes in automated karyotyping.
Since the introduction of the automated karyotyping systems, segmentation and classification of touching and overlapping chromosomes in the metaphase images are major challenges. The earlier reported techniques for disentangling the chromosome overlaps have limited success and use only color information in case of multispectral imaging. Most of them are restricted to separation of single overlap of two chromosomes. This paper introduces a novel algorithm to extricate overlapping chromosomes in a metaphase image. The proposed technique uses Delaunay triangulation to automatically identify the number of overlaps in a cluster followed by the detection of the appropriate cut-points. The banding information on the overlapped region further resolves the set of overlapping chromosomes with the identified cut-points. The proposed algorithm has been tested with four data sets of 60 overlapping cases, obtained from publically available databases and private genetic labs. The experimental results provide an overall accuracy of 75–100 % for resolving the cluster of 1–6 overlaps.


Dietary High Glycinin Reduces Growth Performance and Impairs Liver and Intestinal Health Status of Orange-Spotted Grouper (Epinephelus coioides).
The aim of the study was to investigate whether the negative effects of dietary glycinin are linked to the structural integrity damage, apoptosis promotion and microbiota alteration in the intestine of orange-spotted grouper (Epinephelus coioides). The basal diet (FM diet) was formulated to contain 48% protein and 11% lipid. Fish meal was replaced by soybean meal (SBM) in FM diets to prepare the SBM diet. Two experimental diets were prepared, containing 4.5% and 10% glycinin in the FM diets (G-4.5 and G-10, respectively). Triplicate groups of 20 fish in each tank (initial weight: 8.01 ± 0.10 g) were fed the four diets across an 8 week growth trial period. Fish fed SBM diets had reduced growth rate, hepatosomatic index, liver total antioxidant capacity and GSH-Px activity, but elevated liver MDA content vs. FM diets. The G-4.5 exhibited maximum growth and the G-10 exhibited a comparable growth with that of the FM diet group. The SBM and G-10 diets down-regulated intestinal tight junction function genes (occludin, claudin-3 and ZO-1) and intestinal apoptosis genes (caspase-3, caspase-8, caspase-9, bcl-2 and bcl-xL), but elevated blood diamine oxidase activity, D-lactic acid and endotoxin contents related to intestinal mucosal permeability, as well as the number of intestinal apoptosis vs FM diets. The intestinal abundance of phylum Proteobacteria and genus Vibrio in SBM diets were higher than those in groups receiving other diets. As for the expression of intestinal inflammatory factor genes, in SBM and G-10 diets vs. FM diets, pro-inflammatory genes (TNF-α, IL-1β and IL-8) were up-regulated, but anti-inflammatory genes (TGF-β1 and IL-10) were down-regulated. The results indicate that dietary 10% glycinin rather than 4.5% glycinin could decrease hepatic antioxidant ability and destroy both the intestinal microbiota profile and morphological integrity through disrupting the tight junction structure of the intestine, increasing intestinal mucosal permeability and apoptosis. These results further trigger intestinal inflammatory reactions and even enteritis, ultimately leading to the poor growth of fish.


Blockade of prostaglandin E1 hyperthermia by sodium salicylate given into the ventral septal area of the rat brain.
1. Sodium salicylate (30.0 micrograms microliter-1) or artificial cerebrospinal fluid (ACSF) was infused bilaterally into the ventral septal area (v.s.a.) of the unrestrained rat for 1 h before and 1 h after the injection of prostaglandin E1 at a concentration of 20.0 ng microliter-1 into a lateral cerebral ventricle. 2. During control (ACSF) infusions, 200.0 ng of prostaglandin E1 evoked a hyperthermic response (0.95 +/- 0.16 degrees C). During sodium salicylate infusions, the prostaglandin E1-evoked hyperthermia was significantly reduced (P less than 0.025) to 0.31 +/- 0.16 degrees C. 3. The fever index (degrees C h for 1.0 h) during the infusion of sodium salicylate was reduced 66% below that of control infusions (P less than 0.01). 4. These data indicate that sodium salicylate infused in the v.s.a. of rats can antagonize a prostaglandin E-evoked hyperthermia. This suggests that there may be an additional mechanism of action for sodium salicylate antipyresis other than inhibition of prostaglandin E synthesis.


Hybrid films of chitosan, cellulose nanofibrils and boric acid: Flame retardancy, optical and thermo-mechanical properties.
Chitosan (CS), cellulose nanofibrils (CNF) and boric acid, the latter of which was used as flame retardant, were combined in transparent, hybrid films that were produced by solvent casting. The flammability and the thermal stability of the films were studied with respect to the loading of the inorganic component. Chitosan films displayed fire retardancy properties, which were enhanced in the presence of boric acid. CNF films, in contrast to those from chitosan, were readily flammable; however, when combined with boric acid (30w%), they became self-extinguishing. Most remarkably, bicomponent films comprising CNF and chitosan, displayed better fire retardancy than that of neat CS films. Moreover, boric acid improved the thermal stability of the bicomponent films. The tensile strength and Young's modulus of CS, CNF and CS-CNF films improved at intermediate boric acid addition, although a negative effect on elongation was observed.


Morbidity and medication preferences of individuals with headache presenting to a community pharmacy.
To assess the degree of debilitation and the treatment views of individuals with headache presenting to a community pharmacy. Migraine and chronic daily headache are common poorly managed illnesses. Pharmacists recommend an over-the-counter "headache product" to customers more than 53 000 times daily, thus they are well positioned to help those with headache. Pilot project of 22 self-administered surveys of individuals presenting to a community pharmacy with a complaint of headache. Thirteen persons had Migraine Disability Assessment scores of grade III or grade IV. Of the sample population, a substantial minority (41%) did not believe their headaches could be effectively managed with over-the-counter medications, 72% did not feel over-the-counter agents were safer than prescription products, 96% did not indicate that over-the-counter drugs were more effective than prescription drugs, and 50% disagreed that a physician's evaluation was not necessary. Only half of the population was satisfied with their current therapy, and individuals overwhelmingly (91%) wished they could prevent their headaches. The majority of individuals with headache presenting to a community pharmacy had high levels of morbidity and were in need of education regarding the proper role of over-the-counter medications, the advantages of prescription agents, and the benefits of a physician's referral. These preliminary results indicate that community pharmacies are potentially important locations for identification, education, and referral of individuals with headache.


Integrated iseikonic equation for intraocular lens power calculations.
I present a simplified equation to calculate the iseikonic intraocular lens power and the resultant refractive error needed to achieve iseikonia with 5% tolerance limits. Iseikonic lens power calculations are indicated in the presence of a unilateral cataract and a phakic fellow eye. Iseikonia is often achieved by leaving the operated eye more myopic than the fellow eye. The induced myopia, with 5% tolerance limits, ranges from -0.75 +/- 2.75 diopters (D) for a posterior chamber lens to -2.40 +/- 2.75 D for an anterior chamber lens.


[Trauma of the interorbital space. Pathology and therapy of traumatic telecanthus. 1. Pathology].
Converse is using the term "interorbital space" for the ethmoid bone, especially its lateral wall. We added the frontal process of the upper jaw including spongy substance ("trajector"). Pathophysiology and clinical points of view of comminuted fractures are demonstrated.


Selected hematological, biochemical, and acid-base variables of Paso Fino horses living at different altitudes.
This study aimed at describing selected hematological, biochemical, and acid-base variables of adult horses living at sea level and comparing them to those living at 5 different altitudes. One hundred and thirty-eight healthy Paso Fino horses > 2 years old were enrolled. Altitudes included the following: altitude A (0 to 50 m above sea level, masl; n = 23), B (1000 to 1050 masl; n = 25), C (1450 masl; n = 30), D (1950 to 2050 masl; n = 30), and E (2950 to 3100 masl; n = 30). A portable blood gas analyzer was used to determine selected biochemical and acid-base variables. Hematocrit (Htc) was measured by blood centrifugation and total plasma protein as total solids using a refractometer. A one-way ANOVA with Tukey's HSD post hoc test or a Wilcoxon signed-rank test, depending of the normality of the data, was conducted to compare groups. Horses at sea level had lower Htc (25% ± 2) and Hb (8 ± 0.8 mg/dL) concentration than those horses living ≥ 1000 masl (P < 0.05, for all comparisons). No differences in Htc and Hb were identified in horses living between 1000 and 3000 masl (P > 0.05, for all comparisons). The venous PvCO2 was significantly lower in horses living at altitudes ≥ 1000 masl than those living at 0 masl (42 ± 4.8 mmHg) (P = 0.001, for all comparisons). No differences in PvCO2 were identified in horses living between 1000 and 3000 masl. This study showed that the Htc, Hb, and PvCO2 of horses living at sea level were different compared to those in healthy horses living at altitudes ≥ 1000 masl. However, differences in TPP and electrolyte concentrations were not identified.


Magnetic resonance imaging patterns of treatment-related toxicity in the pediatric brain: an update and review of the literature.
Treatment-related neurotoxicity is a potentially life-threatening clinical condition that can represent a diagnostic challenge. Differentiating diagnoses between therapy-associated brain injury and recurrent disease can be difficult, and the immediate recognition of neurotoxicity is crucial to providing correct therapeutic management, ensuring damage reversibility. For these purposes, the knowledge of clinical timing and specific treatment protocols is extremely important for interpreting MRI patterns. Neuroradiologic findings are heterogeneous and sometimes overlapping, representing the compounding effect of the different treatments. Moreover, MRI patterns can be acute, subacute or delayed and involve different brain regions, depending on (1) the mechanism of action of the specific medication and (2) which brain regions are selectively vulnerable to specific toxic effects. This review illustrates the most common radiologic appearance of radiotherapy, chemotherapy and medication-associated brain injury in children, with special focus on the application of advanced MRI techniques (diffusion, perfusion and proton spectroscopy) in the diagnosis of the underlying processes leading to brain toxicity.


5-HTTLPR moderates the association between attention away from angry faces and prospective depression among youth.
Attention bias to emotion has been studied as a risk factor associated with depression. No study has examined whether attention bias within the context of measured genetic risk leads to increased risk for clinical depressive episodes over time. The current study investigated whether genetic risk, as indexed by the serotonin-transporter-linked polymorphic region (5-HTTLPR), moderated the relationship between attention bias to emotional faces and clinical depression onset prospectively across 18-months in a community sample of youth (n = 428; mean age = 11.97, SD = 2.28; 59% girls). Youth who attended away from angry emotional faces and were homozygous for the S allele of the 5-HTTLPR polymorphism were at greater risk for prospective depressive episode onset. The current study's findings highlight the importance of examining risk for depression across multiple levels of analysis and demonstrate attention away from threat as a possible point of intervention related to attention bias modification and depression treatment among youth.


Axillary vein thrombosis in a female backpacker: Paget-Schroetter syndrome.
In 1875 Sir James Paget reported the first case of primary axillary vein thrombosis. Since then numerous reports of axillary vein thrombosis have appeared citing various initiating events and possible causes. We report here a patient with axillary vein thrombosis. The thrombosis appears to have been provoked by carrying a backpack.


Haloperidol increases smoking in patients with schizophrenia.
Ten patients with schizophrenia participated in 120-min free-smoking sessions when actively psychotic and free of antipsychotic medications, and again after the initiation of haloperidol treatment. During these free-smoking sessions they had access to cigarettes ad libitum. Their expired air carbon monoxide (CO) and plasma nicotine and cotinine levels were measured at the end of the 120-min free-smoking sessions. These patients smoked more after starting haloperidol treatment, relative to their baseline rate of smoking when free of antipsychotic medications, as evidenced by significantly higher expired CO and plasma nicotine levels.


Beta-blockers and weight change in patients with chronic heart failure.
There is an inverse association between body mass and mortality in patients with chronic heart failure (CHF). Beta-blockers have been associated with weight gain. We wanted to examine the relation between beta-blocker use and weight in a population of patients with CHF. We weighed 276 patients presenting with CHF (mean age 71.3 ± 9.5 years, 72.8% male). None were taking a beta-blocker at presentation, but all had started by 4 months' follow-up. The patients were reweighed after 1 year. There was an increase in weight (0.9 ± 7.0 kg; P = .03) and body mass index (0.2 ± 2.4 kg/m(2); P = .02). Patients in New York Heart Association (NYHA) functional class III or IV had no significant weight change, whereas those in class I or II had an increase of 1.62 kg (P < .0001). In patients who had no peripheral edema at baseline or 1 year, there was a greater increase in weight (1.3 ± 6.9 kg; P = .01). Beta-blocker use and intensification of heart failure treatment is associated with weight gain in CHF. The increase is greater in those who are nonedematous and tends to occur in patients with NYHA functional class I and II symptoms.


Glial fibrillary acidic protein mutations in adult-onset Alexander disease: clinical features observed in 12 Japanese patients.
To clarify the clinical manifestations of adult-onset Alexander disease (AOAD) in Japanese patients with glial fibrillary acidic protein (GFAP) gene mutations. Twelve patients of AOAD with GFAP mutations detected in our centre were examined for neurological and magnetic resonance imaging (MRI) findings. Major symptoms were pyramidal and bulbar signs. In addition, three patients presented abnormal behaviour and/or memory disturbance. Two of the three patients also had Parkinsonism and had been diagnosed with fronto-temporal dementia or progressive supranuclear palsy until GFAP mutations were detected. Abnormalities of the medulla oblongata and cervical spinal cord were observed on MRI in all patients. Patients presenting with pyramidal and/or bulbar signs with abnormalities of the medulla oblongata and cervical spinal cord on MRI should be considered for GFAP analysis as this is the typical presentation of AOAD. Abnormal behaviour and cognitive disorders including deterioration of memory were rare symptoms but could be an obstacle to diagnosing Alexander disease.


Correlation of structural extracellular polymeric substances in the mesh biofilms with solids retention time and biofilm hydraulic resistance in dynamic membrane bioreactors.
Dynamic membrane bioreactor (DMBR), which mainly relied on the in-situ formed biofilms on support materials with large aperture (e.g., nylon mesh) to separate fine particles in wastewater, has attracted a lot of attentions due to low cost. The filtration performance of DMBR is mainly determined by the structure and hydraulic resistance of biofilms formed on the mesh. Therefore, understanding the correlation of operation conditions with mesh biofilm compositions and permeability are critically important for optimizing DMBR operation. In present study, how structural extracellular polymeric substances, including alginate-like extracellular polysaccharide (ALE) and amyloid-like protein (AP), in mesh biofilms correlate to solids retention time (SRT) and biofilm structures was explored in DMBRs. At 5d-SRT, compact and gel-like mesh biofilms were formed with a high specific filtration resistance (SFR) of 459 × 109 m/g, while at 40d-SRT porous mesh biofilms were developed with a low SFR of 24 × 109 m/g. Consequently, the 5d-SRT MBR experienced more rapid rise in transmembrane pressure. Further studies found that the 5d-SRT mesh biofilms had a higher AP content, which was positively correlated to biofilm hydraulic resistance. On the contrary, the 40d-SRT mesh biofilms contained a higher content of ALE, suggesting that ALE was negatively correlated to biofilm hydraulic resistance. Therefore, AP instead of ALE likely played a more important role in the formation of compact and gel-like mesh biofilms.


Interaction between the long-latency stretch reflex and voluntary electromyographic activity prior to a rapid voluntary motor reaction.
The size of the long-latency component of the stretch reflex has been examined in the time interval between a signal to move and the required rapid voluntary contraction of triceps and flexor pollicis longus in 8 normal subjects. Bilateral movements of the elbow and thumb were made following an auditory signal. In 50% of the trials a torque pulse was applied unilaterally in order to elicit a stretch reflex response in one arm. The voluntary response in the contralateral arm was uncorrupted by a stretch reflex response, so was used as an indicator of voluntary reaction time. Control experiments, using an electrical stimulus to the fingers rather than muscle stretch, verified that both arms reacted almost simultaneously to the auditory cue, even when the reaction time was shortened by the presence of a unilateral electrical stimulus. Similarly, an interposed muscle stretch stimulus considerably reduced the reaction time to the audio signal. Because of this, the start of the voluntary EMG response frequently 'over-lapped' the end of the long-latency stretch reflex. Failure to take this shortening of voluntary reaction time into consideration can lead to the erroneous conclusion that reflex gain is increased prior to a rapid movement. If the 'overlap' of EMG responses is accounted for, very little change in the size of the long-latency stretch reflex is evident prior to activation of the muscles responsible for the movement of either the elbow or the thumb.


Time resolved analysis of water drainage in porous asphalt concrete using neutron radiography.
Porous asphalt as a road surface layer controls aquaplaning as rain water can drain through its highly porous structure. The process of water drainage through this permeable layer is studied using neutron radiography. Time-resolved water configuration and distribution within the porous structure are reported. It is shown that radiography depicts the process of liquid water transport within the complex geometry of porous asphalt, capturing water films, filled dead end pores and water islands.


Lipid bilayer composition as a determinant of cancer cell sensitivity to tumoricidal protein-lipid complexes.
Complexes formed by the alpha1 N-terminal peptide of alpha-lactalbumin and oleic acid (alpha1-oleate) interact with lipid bilayers. Plasma membrane perturbations trigger tumor cell death but normal differentiated cells are more resistant, and their plasma membranes are less strongly affected. This study examined membrane lipid composition as a determinant of tumor cell reactivity. Bladder cancer tissue showed a higher abundance of unsaturated lipids enriched in phosphatidylcholine, PC (36:4) and PC (38:4), and sphingomyelin, SM (36:1) than healthy bladder tissue, where saturated lipids predominated and the lipid extracts from bladder cancer tissue inhibited the tumoricidal effect of the complex more effectively than healthy tissue extracts. Furthermore, unsaturated PC in solution inhibited tumor cell death, and the complex interacted with giant unilamellar vesicles formed by PC, confirming the affinity of alpha1-oleate for fluid membranes enriched in PC. Quartz Crystal Microbalance with dissipation monitoring (QCM-D) detected a preference of the complex for the liquid-disordered phase, suggesting that the insertion into PC-based membranes and the resulting membrane perturbations are influenced by membrane lipid saturation. The results suggest that the membrane lipid composition is functionally important and that specific unsaturated membrane lipids may serve as "recognition motifs" for broad-spectrum tumoricidal molecules such as alpha1-oleate.


Trans-saccadic priming in hemianopia: sighted-field sensitivity is boosted by a blind-field prime.
We experience visual stability despite shifts of the visual array across the retina produced by eye movements. A process known as remapping is thought to keep track of the spatial locations of objects as they move on the retina. We explored remapping in damaged visual cortex by presenting a stimulus in the blind field of two patients with hemianopia. When they executed a saccadic eye movement that would bring the stimulated location into the sighted field, reported awareness of the stimulus increased, even though the stimulus was removed before the saccade began and so never actually fell in the sighted field. Moreover, when a location was primed by a blind-field stimulus and then brought into the sighted field by a saccade, detection sensitivity for near-threshold targets appearing at this location increased dramatically. The results demonstrate that brain areas supporting conscious vision are not necessary for remapping, and suggest visual stability is maintained for salient objects even when they are not consciously perceived.


Preoperative Dye Localization for Thoracoscopic Lung Surgery: Hybrid Versus Computed Tomography Room.
Preoperative computed tomography (CT)-guided dye localization is essential for the surgical treatment of small lung nodules and is mostly performed by radiologists in the CT room. Several studies reported their early experiences of preoperative localization in the hybrid operating room. A comparison between localization in the CT room and hybrid room has not been reported. Therefore, we compared the outcomes of preoperative localization in the hybrid and CT rooms. This study included patients who underwent preoperative CT-guided dye localization for thoracoscopic lung tumor surgery in the hybrid operation room (n = 25) and CT room (n = 283) at our institute. Propensity matched analysis, incorporating nodule size, number, and depth, and operation method, was used to compare the short-term outcomes of these two groups. Each patient in the hybrid room group was matched with 2 patients in the CT room group. Localization was successfully performed in 23 patients (92%) and 50 patients (100%) in the hybrid room and CT room groups, respectively. There was no significant difference in demographics between groups. In the hybrid room group, the global time was shorter (192.6 versus 244.1 minutes, p = 0.003), and the localization time was longer (33.1 versus 22.3 minutes, p < 0.001). All lung nodules were successfully resected in both groups, but the hybrid room group had a relatively higher morbidity rate. The hybrid operating room may be associated with a shorter global time and similar perioperative and postoperative outcomes compared with the CT room. Localization in the hybrid operating room seems an effective alternative method for managing small lung nodules.


The Amotl2 gene inhibits Wnt/β-catenin signaling and regulates embryonic development in zebrafish.
The Motin family proteins can regulate cell polarity, cell mobility, and proliferation during embryonic development by controlling distinct signaling pathways. In this study, we demonstrate that amotl2 knockdown in zebrafish wild-type embryos results in embryonic dorsalization, and this effect can be antagonized by co-knockdown of the dorsal inducer β-catenin2. Overexpression of amotl2 in masterblind (mbl) homozygous embryos, in which canonical Wnt signaling is up-regulated due to an axin1 mutation, transforms eyeless phenotype into smaller eyes, whereas co-knockdown of amot, amotl1, and amotl2 leads to development of smaller eyes in mbl heterozygotes. In cultured mammalian cells, Motin family members all possess the ability to attenuate Wnt/β-catenin signaling. Focusing on Amotl2, we show that Amotl2 can associate with and trap β-catenin in the Rab11-positive recycling endosomes, and as a result, the amount of β-catenin in the cytosol and nucleus is reduced. Thus, our findings provide novel insights into functions of Motin family members and regulation of Wnt/β-catenin signaling.


Longitudinal assessment of symptom severity among hospitalized elders diagnosed with cancer, heart failure, and chronic obstructive pulmonary disease.
Pain, dyspnea, and anxiety are common among patients with cancer, heart failure (HF), and chronic obstructive pulmonary disease (COPD), yet little is known about the severity of symptoms over time. To determine the prevalence, severity, burden, and predictors of symptoms during the course of hospitalization and at 2 weeks after discharge. A prospective cohort study. A large academic university. Patients were 65 years or older with a primary diagnosis of cancer, COPD, or HF. Daily living skills and depression were recorded at enrollment. Symptoms were assessed daily and 2 weeks postdischarge. At baseline, most participants reported moderate/severe pain (54%), dyspnea (53%), and anxiety (62%). Almost two-thirds (64%) had 2 or more symptoms at a moderate/severe level. The prevalence of moderate/severe symptoms decreased at the 24-hour assessment (pain = 42%, dyspnea = 45%, anxiety = 55%, burden = 55%) and again at follow-up (pain = 28%, dyspnea = 27%, anxiety = 25%, burden = 30%). While there was no association between primary diagnosis and symptom severity at baseline or 24-hour assessment, at 2-week follow-up, a higher percentage of patients with COPD had moderate/severe pain (54%, χ(2) = 22.0, P = 0.001), dyspnea (45%, χ(2) = 9.3, P = 0.05), and overall symptom burden (55%, χ(2) = 25.9, P = 0.001) than those with cancer (pain = 22%, dyspnea = 16%, symptom burden = 16%) or HF (pain = 25%, dyspnea = 24%, symptom burden = 28%). Predictors of symptom burden at follow-up were COPD (odds ratio [OR] = 7.5; 95% confidence interval [CI] = 2.0, 27.7) and probable depression (OR = 6.1; 95% CI = 2.1, 17.8). The majority of inpatients with chronic illness reported high severity of symptoms. Symptoms improved over time but many patients, particularly those with COPD, had high symptom severity at follow-up.


Ethical and legal implications of cancer genetic testing: do physicians have a duty to warn patients' relatives about possible genetic risks?
This vignette raises questions about the extent of physicians' obligations to warn relatives of a patient about a hereditary cancer risk.


Claudication in an adolescent with a hypoplastic femur.
The most common cause of claudication is atherosclerosis obliterans. However, when it presents in adolescence, other causes should be considered. We describe the case of a 15-year-old girl who had severe intermittent claudication 8 years after a limb-lengthening procedure for a hypoplastic femur. The lesion responsible was an isolated fibromuscular dysplastic segment of the distal superficial femoral artery and proximal popliteal artery. The etiology, treatment, and histopathology are discussed.


The O-RADS MRI score for the characterization of indeterminate ovarian masses: From theory to practice.
This article reviews the Ovarian-Adnexal Reporting Data System Magnetic Resonance Imaging (O-RADS MRI) score for the characterization of indeterminate ovarian masses. We aim to provide sufficient information to enable readers to apply the score efficiently in clinical practice. To this end, we review the indications of the O-RADS MRI score and the specific MRI protocol that must be applied. We review all the categories of the score, illustrating them through examples. Finally, we show the most common errors and pitfalls during the learning curve, providing the keys to avoiding them.


The Human Ecological Perspective and Biopsychosocial Medicine.
With regard to philosophical anthropology, a human ecological framework for the human-environment relationship as an "ecology of the person" is outlined, which focuses on the term "relationship" and aims to be scientifically sound. It also provides theoretical orientations for multiprofessional clinical work. For this purpose, a multi-dimensional basic grid for the characterization of the individual human being is proposed. The necessity and meaningfulness of a differentiation and systematization of the terms "environment", and above all "relationship", are demonstrated, and practical examples and links to similar framework models are given.


Household aggregation of Strongyloides stercoralis infection in Bangladesh.
Strongyloides stercoralis infections were shown to be aggregated in households in an urban slum community in Dhaka, Bangladesh. Parasitological data on 880 residents living in 280 households were analysed statistically using 3 different tests, each of which yielded significant evidence of household aggregation of S. stercoralis infection. One test was applied to the data after stratification for 4 variables were previously shown to be independently associated with infection. Evidence of household aggregation of infection remained after stratification, suggesting that aggregation is due not only to shared risk factors, but also to either familial genetic predisposition to infection or close contact person to person transmission of infection within households.


Quantitation of interaction of anti-metatype monoclonal antibodies specific for the variable regions of a high affinity liganded monoclonal antibody.
Four hamster monoclonal anti-metatype antibodies were characterized in terms of their binding properties with liganded murine monoclonal single-chain antifluorescein antibody 4-4-20. Based on induced delays in the rate of ligand (fluorescein) dissociation upon the binding of each monoclonal anti-Met antibody, apparent Kd values were determined for monoclonal antibodies 3A5-1, P1E11, 4A6, and 2C3 (3.6 x 10(-8), 3.6 x 10(-8), 5.0 x 10(-8), and 2.6 x 10(-7) M, respectively). The interaction of hamster monoclonal antibody 3A5-1 with liganded SCA 4-4-20 and IgG 4-4-20 was also evaluated on the basis of deuterium oxide exchange to assess the relative ability of each antibody to stabilize the intrinsic dynamics of the variable domains of the single-chain molecule. The results indicated a correlation between the apparent Kd of the monoclonal anti-Met antibody and the degree of delay in the rate of ligand dissociation from the primary antibody.


Plant interactions for pollinator visits: a test of the magnet species effect.
From 1985-1987, patterns of fruit and seed set were studied in a population of mayapple (Podophyllum peltatum), a clonal, self-incompatible herb found in deciduous woods in eastern North America. Mayapple flowers do not produce nectar, but depend on infrequent visits by nectar-seeking queen bumble bees for pollination. In all years female reproductive success in mayapple colonies was influenced by colony size (number of flowers), by the distance to neighbouring colonies and by proximity to lousewort plants (Pedicularis canadensis), a prolific nectar producer heavily visited by bumble bees. In all years fruit and seed set were greater in mayapple colonies <25 m from lousewort flowers than in matched colonies which were >50 m from lousewort. In 1985 and 1987 the frequency of queen bumble bee visits to flowers in colonies close to lousewort was about four times greater than to distant colonies. In 1986 I removed about 80% of lousewort flowers to test whether the enhanced fruit and seed set in mayapples close to lousewort was pollinator mediated. Mayapple colonies close to flowerless lousewort patches did not differ in fruit or seed set from matched colonies >50 m from lousewort. In contrast, mayapples close to flowering lousewort patches had greater fruit and seed set compared with distant colonies. Over all years, a larger proportion of mayapples close to flowering lousewort patches had enhanced fruit and seed set compared with colonies close to louseworts without flowers. Though rarely documented, this type of facilitative interaction between plants that are highly attractive to pollinators ("magnet" species), and co-flowering species that are rarely visited by pollinators, may be widespread in plant communities.


Maternally transferred mercury in wild largemouth bass, Micropterus salmoides.
Maternal transfer of mercury in fish represents a potential route of elimination for adult females and a risk to developing embryos. To better quantify maternal transfer, we measured Hg in female largemouth bass (Micropterus salmoides) muscle and eggs from six waterbodies. Mercury in eggs from two waterbodies exceeded a US federal screening level (0.3 μg g(-1)) and was likely high enough to cause adverse reproductive effects. We found a curvilinear relationship between female and egg Hg. Fish with <0.37 μg g(-1) Hg had low levels of Hg in eggs; those with Hg >0.37 μg g(-1) showed a direct relationship between egg and muscle Hg (Log10 egg Hg = -1.03 + 1.18 * log10 muscle tissue Hg + 2.15 * (log10 muscle tissue Hg + 0.35)(2)). We also report higher maternal transfer (0.2-13.2%) and higher ratios of egg to muscle tissue Hg (4-52%) and egg to whole body Hg concentrations (7-116%) than previously observed for teleost fish.


The effect of hip muscle weakness and femoral bony deformities on gait performance.
Children with cerebral palsy (CP) present with a pathological gait pattern due to musculoskeletal impairments, such as muscle weakness and altered bony geometry. However, the effect of these impairments on gait performance is still unknown. Research aim:This study aimed to explore the effect of hip muscle weakness and femoral deformities on the gait performance of CP and typical developing (TD) subjects. 6400 musculoskeletal models were created by weakening the hip extensors, abductors, adductors and flexors from 0% to 75 % and increasing the femoral anteversion angle (FAA) and neck shaft angle (NSA) from 20° to 60° and 120° to 160°, respectively. One TD and five CP gait patterns were imposed to each model and muscle forces were calculated. The effect of weakness and bony deformities on the capability gap (CG) at the hip, i.e. the lack in hip moment generating capacity to perform the gait pattern, was investigated using regression analysis. The CG of apparent equinus, stiff knee gait, TD gait, jump gait and true equinus increased with 0.080, 0.038, 0.015, 0.023 and 0.005 Nm/kg per 10 percent hip abductor weakness increase, with 0.211, 0.130, 0.056, 0.045 and 0.011 Nm/kg per 10 degrees FAA increase and with 0.163, 0.080, 0.036, 0.043 and 0.011 Nm/kg per 10 degrees NSA increase, respectively. Combined weakness and bony deformities explained 96 %, 85 %, 82 %, 65 %, 40 % and 35 % of the variance in the CG of apparent equinus, TD gait, stiff knee gait, jump gait, true equinus and crouch gait, respectively. The results suggest that surgical correction of femoral deformities is more likely to be effective than strength training of hip muscles in enhancing CP gait performance. Jump gait, true equinus and especially crouch were more robust, while apparent equinus and stiff knee gait were limited by hip weakness and femoral deformities.


[Update: transitional fractures : Osseous injuries in growing up adolescents-correct nomenclature, radiological diagnostics and treatment].
Transitional fractures are special forms of epiphyseal injuries in adolescents in whom the growth plate is already partially closed. Due to the partial ossification specific stereotypical fracture patterns can develop, which can be differentiated into twoplane, triplane I and triplane II fractures, depending on the involvement of the metaphysis and the number of fragments. At the beginning of the diagnostics conventional projection radiography in two planes is used; however, due to the complex fracture patterns computed tomography (CT) is often indicated, also for preoperative planning. The treatment depends on the extent of the fracture dislocation, which should be an integral part of the radiological findings, as dislocation of fragments less than 2 mm in size are usually treated conservatively. Prognostically relevant is above all the reconstruction of the joint surfaces, as early arthrosis can be a threat if the incongruity remains-relevant growth disturbances in the case of growth joint closure that has already begun are usually no longer expected.


Allelic imbalance analysis of oral tongue squamous cell carcinoma by high-density single nucleotide polymorphism arrays using whole-genome amplified DNA.
Multiple displacement-based whole-genome DNA amplification is a promising tool to obtain sufficient DNA from small tissue specimens for various genetic analyses, such as SNP array-based analysis. Using Affymetrix 10 K and 100 K SNP mapping array, we evaluated the performance of the Phi29 DNA polymerase-based genome amplification. Greater than 99% concordance in genotyping calls were achieved between amplified and non-amplified DNAs for both arrays. By utilizing the Affymetrix GeneChip Chromosome Copy Number Tool, the allelic imbalance profiles for the advanced stage oral tongue squamous cell carcinoma (OTSCC) were generated based on 10 K and 100 K SNP mapping array results. The results from these two array platforms agree closely, but more precise allelic imbalance patterns can be revealed from the 100 K SNP mapping array data. Furthermore, our data suggested a frequent loss at 3p11-p12 for advanced stage OTSCC.


Comparison of oral human papilloma virus detection methods among Hispanic adults.
Oral human papilloma virus (HPV) infection is associated with nearly three-quarters of all oropharyngeal cancers in the United States. Research also suggests its association with periodontal disease. There are limited studies evaluating differences in HPV detection methods; however, oral rinse is considered the most sensitive detection method. We compared HPV detection by self-collected oral rinse versus self-collected cytobrush and assessed whether the strength of association between periodontitis and HPV is modified by the collection method. Data from a cross-sectional study of Hispanic adults in Puerto Rico (n = 346) who provided oral rinse and cytobrush samples for oral HPV detection and were clinically evaluated for periodontitis. The agreement between the oral mouthwash and cytobrush methods was assessed using the Kappa (κ) statistic. Logistic regression models were used to determine if the association between HPV infection and other risk factors varied by oral sample collection method. HPV prevalence was slightly higher using cytobrush than oral rinse (5.8% vs. 4.3%). The sensitivity of cytobrush to detect oral HPV was 64.7%, and the specificity was 97.4%. We observed a κ of 0.61 (95% confidence interval [CI]: 0.45-0.78), indicative of fair to good agreement between the two collection methods. The association between oral HPV infection and periodontitis severity was stronger when using the oral rinse collection method (odds ratio [OR] = 3.23, 95% CI: 1.06-9.84); the association was not statistically significant for cytobrush (OR = 1.96, 95% CI: 0.68-5.65). These findings support the significance of choosing the most suitable collection method in oral HPV-related studies. Selecting the most appropriate collection method is an essential criterion in oral HPV-related studies.


The effects of dry-land strength training on competitive sprinter swimmers.
This study aimed to examine the effects of eight weeks of dry-land strength combined with swimming training on the development of upper and lower body strength, jumping ability, and swimming performance in competitive sprinter swimmers. Twenty (14 men and 6 women) university swimmers of national-level (age: 20.55 ± 1.76 years, body mass: 68.86 ± 7.69 kg, height: 1.77 ± 0.06 m, 100 m front crawl: 71.08 ± 6.71s, 50 m front crawl: 31.70 ± 2.45s) were randomly divided into two groups: experimental group (EG: 11) and control group (CG: 9). In addition to the usual in-water training (3-4 sessions per week of ∼80 min), the EG performed 8 weeks (one session per week) of strength-training (ST). The ST included bench press, full squat, countermovement jumping, countermovement jumping with free-arm movement, and the medical ball throwing. Stroke length, stroke frequency, stroke index, and swimming velocity were recorded during 50 and 100 m front crawl time-trials. Strength and swimming performance were evaluated before and after 8 weeks of training. The results showed a significant improvement in sprint performance (50 m: p < 0.01, d = 0.47; 100 m: p < 0.05, d = 0.42), stroke frequency (50 m: p < 0.01, d = 0.90) and stroke index (100 m: p < 0.01, d = 0.29) in the EG. Despite both groups' increased strength performance, increases in bench press were higher in the EG (p < 0.001, d = 0.75) than CG (p = 0.05, d = 0.34). Complementing in-water training with strength training seems to be relevant to improve upper body strength and to optimize 50 m and 100 m swimming performance, adapting technical patterns used during all-out swimming.


TUBB3 E410K syndrome: Case report and review of the clinical spectrum of TUBB3 mutations.
The tubulinopathies refer to a wide range of brain malformations caused by mutations in one of the seven genes encoding different tubulin's isotypes. The β-tubulin isotype III (TUBB3) gene has a primary function in nervous system development and axon generation and maintenance, due to its neuron-specific expression pattern. A recurrent heterozygous mutation, c.1228G > A; p.E410K, in TUBB3 gene is responsible of a rare disorder clinically characterized by congenital fibrosis of the extraocular muscle type 3 (CFEOM3), intellectual disability and a wide range of neurological and endocrine abnormalities. Other mutations have been described spanning the entire gene and genotype-phenotype correlations have been proposed. We report on a 3-year-old boy in whom clinical exome sequencing allowed to identify a de novo TUBB3 E410K mutation as the molecular cause underlying a complex phenotype characterized by a severe bilateral palpebral ptosis refractory to eye surgery, psychomotor delay, absent speech, hypogonadism, celiac disease, and cyclic vomiting. Brain MRI revealed thinning of the corpus callosum with no evidence of malformation cortical dysplasia. We reviewed available records of patients with TUBB3 E410K mutation and compared their phenotype with the clinical outcome of patients with other mutations in TUBB3 gene. The present study confirms that TUBB3 E410K results in a clinically recognizable phenotype, unassociated to the distinct cortical dysplasia caused by other mutations in the same gene. Early molecular characterization of TUBB3 E410K syndrome is critical for targeted genetic counseling and prompt prospective care in term of neurological, ophthalmological, endocrine, and gastrointestinal follow-up.


The fragile-X syndrome.
The variability in behavioral manifestations of the fragile-X syndrome and the lack of a well-defined psychological profile require the attention of behavioral geneticists and other behavioral scientists. The association with autism suggests that the fra(X) may be responsible for a genetic subtype of autism. While the fragile-X syndrome is considered an X-linked disorder, several aspects of observed transmission patterns do not follow those of classical X-linked inheritance. In particular, the finding of genetic transmission via intellectually normal males is surprising and has important implications for genetic counseling, as well as for genetic models of the fragile-X syndrome. Reports on folic acid treatment are encouraging, but not conclusive. The mechanisms involved in the association between the fra(X) chromosome and its particular phenotype are still unknown. Current investigations applying advanced techniques in molecular biology are likely to provide insight into this unique genetic disorder.


Laser scanning-based tissue autofluorescence/fluorescence imaging (LS-TAFI), a new technique for analysis of microanatomy in whole-mount tissues.
Intact organ structure is essential in maintaining tissue specificity and cellular differentiation. Small physiological or genetic variations lead to changes in microanatomy that, if persistent, could have functional consequences and may easily be masked by the heterogeneity of tissue anatomy. Current imaging techniques rely on histological, two-dimensional sections requiring sample manipulation that are essentially two dimensional. We have developed a method for three-dimensional imaging of whole-mount, unsectioned mammalian tissues to elucidate subtle and detailed micro- and macroanatomies in adult organs and embryos. We analyzed intact or dissected organ whole mounts with laser scanning-based tissue autofluorescence/fluorescence imaging (LS-TAFI). We obtained clear visualization of microstructures within murine mammary glands and mammary tumors and other organs without the use of immunostaining and without probes or fluorescent reporter genes. Combining autofluorescence with reflected light signals from chromophore-stained tissues allowed identification of individual cells within three-dimensional structures of whole-mounted organs. This technique could be useful for rapid diagnosis of human clinical samples and possibly the effect of subtle variations such as low dose radiation.


[Genetic polymorphisms of short tandem repeats loci F13A01, FESFPS, vWA from Han population in Guizhou].
To understand the allele structure and genetic polymorphism at F13A01, FESFPS and vWA short tandem repeats (STRs) loci for Han population in Guizhou province of China, and to construct a preliminary database. One hundred sixty unrelated individuals in Han population from Guizhou were analyzed by multiplex polymerase chain reaction. The resultant allele frequencies were compared with those of other population or race database. The genotype distributions of F13A01, FESFPS and vWA were in accordance with Hardy-Weinberg equilibrium. The combined discrimination power and polymorphism information content were 0.9984 and 0.9700 respectively. All of the three loci in this study provide useful markers for forensic paternity test and for genetic purposes.


Characterisation of an evolutionary conserved protein interacting with the putative guanine nucleotide exchange factor DelGEF and modulating secretion.
A human cDNA library was screened for proteins interacting with the deafness locus putative guanine nucleotide exchange factor (DelGEF) using a yeast two-hybrid system. A protein with a predicted size of 9 kDa was identified as a binding partner, this protein was designated DelGEF interacting protein 1 (DelGIP1). The interaction between DelGEF and DelGIP1 was verified by co-immunoprecipitation of a DelGEF-DelGIP1 complex from cell lysates. Highly conserved homologues of DelGIP1 were identified in higher and lower eukaryotes by database searching. The human DelGIP1 gene is ubiquitously expressed as judged by human multiple tissue Northern blot analysis. DelGEF was recently shown to interact with Sec5, a protein involved in secretion, and to regulate secretion of proteoglycans. Downregulation of endogenous DelGIP1 in HeLa cells induced increased extracellular secretion of proteoglycans indicating a possible role for DelGIP1 in the secretion process.


Self-induced pneumoparotitis in an adolescent. Report of a case and review of the literature.
Pneumoparotitis is a rare cause of parotid inflammatory disease in both adults and children. A 12-year-old girl is reported who presented with recurrent bilateral parotid swelling. Radiologic evaluation revealed pneumoparotitis associated with masseter muscle hypertrophy. Further investigation revealed the self-induced nature of the condition in this teenager. Self-induced pneumoparotitis has been reported almost exclusively in adolescents who often have psychosocial problems. The clinical presentation, proposed pathophysiology, diagnosis and management of this rare condition are discussed and a review of the literature is presented.


Development, testing, and national evaluation of a pediatric Patient-Family-Centered Care benchmarking survey.
This study provides evidence for reliability (the Cronbach alpha of .76-.94) and construct validity of the Patient-Family-Centered Care Survey developed by the researchers in collaboration with FKP Architects, used to measure and benchmark practice within pediatric institutions. The survey evaluates progress of integrating patient-family-centered care over time and can be triangulated with measurements of desired patient and institutional outcomes.


Psychosocial interventions for adolescents and young adult cancer patients: A systematic review and meta-analysis.
Adolescent and young adult (AYA) cancer patients experience unique psychosocial needs and developmental challenges. A cancer diagnosis can stress this development and disrupt AYAs in their normal life. The aim of this systematic review and meta-analysis was to assess the impact of psychosocial interventions on mental health in AYAs. A literature research was conducted, which resulted in twelve eligible studies. The standardized mean difference between intervention and control conditions was 0.13 (95% CI: -0.16 to 0.42) for quality of life, 0.27 (95% CI: -0.22 to 0.76) for cancer-related knowledge and -0.16 (95% CI: -0.73 to 0.42) on psychological distress indicating, small and non-significant effects for interventions improving mental health. This work strengthens the need for age-appropriated interventions in psycho-oncology. Future research should develop interventions more graduated by age. Randomized intervention studies with larger samples and focusing psychosocial outcomes are needed to establish evidence-based psycho-oncological interventions for AYAs.


Urinary angiotensinogen level is correlated with proteinuria in renal transplant recipients.
Along with immunologic mechanisms, intrarenal renin-angiotensin system (RAS) activation has been suggested to play a role in the development and progression of chronic allograft injury. In various glomerular diseases, urinary angiotensinogen (AGT) level is a good indicator for the activation of intrarenal RAS. In this study, we aimed to investigate the parameters associated with urinary AGT level in patients with kidney transplantation. Seventy renal transplant patients with stable graft function (≥ 6 months after transplantation, serum creatinine level <2 mg/dL) and 21 healthy volunteers were included in the study. Patients were taking standard triple immunosuppressive treatment. Demographic characteristics of patients and healthy volunteers, drug use, and 24-hour ambulatory blood pressure measurements were recorded. Morning second urine and fasting blood samples were taken from all participants. Serum biochemical markers and urine Na, K, uric acid, creatinine, and protein levels were measured. Urinary AGT levels were determined by enzyme-linked immunosorbent assay. Mean systolic and diastolic blood pressures in patients with renal transplantation were higher than in healthy volunteers. Both urinary AGT-urinary creatinine ratio (UAGT/UCr) and urinary protein-urinary creatinine ratio (UPro/UCr) were higher in kidney transplant patients than in healthy volunteers (P < .01; P < .0001; respectively). In patients with renal transplantation, UAGT/UCr was positively correlated with UPro/UCr and negatively correlated with estimated glomerular filtration rate (eGFR) (r = 0.738; P = .01; and r = -0.397; P = .01; respectively). There was no correlation between UAGT/UCr and other study parameters, including bood pressure levels. Our findings indicate that high urinary excretion of AGT is associated with proteinuria and lower eGFR in kidney transplant recipients without overt chronic allograft injury. These preliminary results encourage us to design a long-term longitudinal analysis using urinary AGT along with multiple markers to obtain early diagnosis and to predict the prognosis of chronic allograft dysfunction.


Therapeutic targeting of FUBP3 phase separation by GATA2-AS1 inhibits malate-aspartate shuttle and neuroblastoma progression via modulating SUZ12 activity.
Malate-aspartate shuttle (MAS) is essential for maintaining glycolysis and energy metabolism in tumors, while its regulatory mechanisms in neuroblastoma (NB), the commonest extracranial malignancy during childhood, still remain to be elucidated. Herein, by analyzing multi-omics data, GATA binding protein 2 (GATA2) and its antisense RNA 1 (GATA2-AS1) were identified to suppress MAS during NB progression. Mechanistic studies revealed that GATA2 inhibited the transcription of glutamic-oxaloacetic transaminase 2 (GOT2) and malate dehydrogenase 2 (MDH2). As a long non-coding RNA destabilized by RNA binding motif protein 15-mediated N6-methyladenosine methylation, GATA2-AS1 bound with far upstream element binding protein 3 (FUBP3) to repress its liquid-liquid phase separation and interaction with suppressor of zest 12 (SUZ12), resulting in decrease of SUZ12 activity and epigenetic up-regulation of GATA2 and other tumor suppressors. Rescue experiments revealed that GATA2-AS1 inhibited MAS and NB progression via repressing interaction between FUBP3 and SUZ12. Pre-clinically, administration of lentivirus carrying GATA2-AS1 suppressed MAS, aerobic glycolysis, and aggressive behaviors of NB xenografts. Notably, low GATA2-AS1 or GATA2 expression and high FUBP3, SUZ12, GOT2 or MDH2 levels were linked with unfavorable outcome of NB patients. These findings suggest that GATA2-AS1 inhibits FUBP3 phase separation to repress MAS and NB progression via modulating SUZ12 activity.


Vertebroplasty comparing injectable calcium phosphate cement compared with polymethylmethacrylate in a unique canine vertebral body large defect model.
Vertebroplasty was developed to mechanically reinforce weakened vertebral bodies. Polymethylmethacrylate (PMMA) bone cement has been most commonly used but carries risks of thermal injury and respiratory and cardiovascular complications. Calcium phosphate (CaP) offers the potential for biological resorption and replacement with new bone, restoring vertebral body mass and height. To compare compressive strength, elastic modulus of the adjacent motion segments, and histologic response of vertebral bodies injected with either CaP or PMMA in a canine vertebroplasty model. By using a canine vertebroplasty model, two level vertebroplasties were performed at L1 and L3 and studied for 1 month (n=10) and 6 months (n=10). In each canine, one vertebral defect was randomly injected with either CaP cement (BoneSource; Stryker, Freiberg, Germany) or PMMA. Twenty dogs had an iatrogenically created cavitary lesion at two nonadjacent levels injected with either CaP or PMMA. Canines from each group were tested mechanically (n=5) and histologically (n=5). Histology consisted of axial sections of the L1 and L3 vertebral bodies and high-resolution contact radiographs. Sections from each specimen were embedded in plastic without decalcification to study the bone-cement interface. Bone-cement interfaces were compared for evidence of necrosis, fibrosis, foreign body response, cement resorption, and new bone formation between the PMMA and CaP treatments groups. Mechanical compression testing was performed on specimens from the 1-month (n=5) and 6-month (n=5) time periods. The T13 vertebral body was used as an intact control for the destructive compression testing of L1 and L3. Each vertebral body was compressed to 50% of its original height under displacement control at 15 mm/min to simulate a nontraumatic loading situation. Force and displacement data were recorded in real time. Vertebral sites containing PMMA were characterized by a thin fibrous membrane. PMMA was detected within the trabeculae, vascular channels, and the spinal canal. Unlike PMMA, CaP underwent resorption and remodeling with vascular invasion and bone ingrowth. Woven and lamellar bone was found on the CaP cement surface, within the remodeled material, and on the surrounding trabeculae. Vertebral body compression strength testing revealed no significant difference in vertebral body height and compressive strength between PMMA and CaP. There was a trend for CaP-treated vertebrae to increase in compressive strength from 1 month to 6 months, whereas PMMA decreased compressive strength when compared with adjacent nontreated vertebrae. For both short and intermediate time periods, the injection of CaP cement can be an effective method to treat large vertebral defects. Early results indicate that CaP remodeling might result in the resorption of the majority of the cement with replacement by lamellar bone.


Anxiety and fear of childbirth as predictors of postnatal depression in nulliparous women.
Perinatal mental health problems have been studied in more than 90% of high income countries but this information is available only for 10% of low and middle income countries. A study on the relationship between anxiety during pregnancy and postpartum depression has not been performed in Iran. This prospective study aimed to investigate whether anxiety and fear of childbirth during pregnancy is an independent predictor of postpartum depressive symptoms. In this prospective longitudinal study participants were 160 women with a gestational age of 28-30 weeks from 10 prenatal care clinics in Qom, Iran. Subjects were interviewed and the State-Trait Anxiety Inventory (STAI) and Childbirth Attitudes Questionnaire (CAQ) were completed at 28 and 38 weeks of gestation. They were followed up 45 days and 3 months after childbirth. Postpartum depression was defined as a score≥13 on the Edinburgh Postpartum Depression Scale (EPDS). Antenatal state anxiety (odds ratio [OR]=3.2; P=0.002 and OR=2.91; P=0.007 at 28 and 38 weeks of gestation, respectively) and trait anxiety (OR=3.33; P=0.001 and OR=3.30; P=0.003 at 28 and 38 weeks of gestation, respectively) increased the risk of postpartum depression 45 days after birth (P<0.05). Likewise, the presence of antenatal state and trait anxiety at 28 and 38 weeks of gestation significantly increased the risk of postpartum depression during the first three months after childbirth (P<0.05). On the contrary, prenatal fear of childbirth was not a significant predictor of postpartum depression symptoms (P>0.05). The findings from this study suggest that antenatal state and trait anxiety, assessed by interview, is an important predictor of postpartum depression. Therefore, it should be routinely screened in order to develop specific preventive interventions.


The Impact of Medicaid Expansion on Early-Stage Hepatocellular Carcinoma Care.
The impact of Medicaid expansion (ME) on hepatocellular carcinoma (HCC) remains controversial, and heterogeneous effects on care processes may relate to sociodemographic factors. We sought to evaluate the association between ME and receipt of surgery in early-stage HCC. Patients diagnosed with early-stage HCC between 40 and 64 years of age were identified from the National Cancer Database and divided into pre- (2004-2012) and post- (2015-2017) expansion cohorts. Logistic regression was used to identify predictors of surgical treatment. Difference-in-difference (DID) analysis assessed changes in surgical treatment between patients living in ME and non-ME states. Among 19,745 patients, 12,220 (61.9%) were diagnosed before ME and 7525 (38.1%) after. Although overall utilization of surgery decreased after expansion (ME, pre-expansion: 62.2% versus post-expansion: 51.6%; non-ME, pre-expansion: 62.1% versus post-expansion: 50.8%, p < 0.001), this trend varied relative to insurance status. Notably, receipt of surgery increased among uninsured/Medicaid patients living in ME states after expansion (pre-expansion: 48.1%, post-expansion: 52.3%, p < 0.001). Moreover, treatment at academic or high-volume facilities increased the likelihood of undergoing surgery before expansion. After expansion, treatment at an academic facility and living in an ME state (OR 1.28, 95% CI 1.07-1.54, p < 0.01) were predictors of surgical treatment. DID analysis demonstrated increased utilization of surgery for uninsured/Medicaid patients living in ME states relative to non-ME states (uninsured/Medicaid: 6.4%, p < 0.05), although no differences were noted among patients with other insurance statuses (overall: 0.7%, private: -2.0%, other: 0.3%, all p > 0.05). Implementation of ME heterogeneously impacted utilization of care in early-stage HCC. Notably, uninsured/Medicaid patients residing in ME states demonstrated increased utilization of surgical treatment after expansion.


The selective staining mechanism of phosphatase producing colonies in the diphosphatephenolphthalein-methyl green method for the detection of bacterial phosphatase activity.
The aim of this study was to explain, in a novel method for the testing of bacterial phosphatase activity (MGP), the mechanism by which, in the presence of a phosphatase substrate and a stain, the phosphatase positive colonies become intensely pigmented while the others remain unstained (Satta et al., 1979). The experiments here described indicate that the products of the phosphatase reaction form, with the stains, high pigmented insoluble complexes that precipitate at the site where the reaction has occurred. Since, in most bacteria, phosphatase are membrane bound, in the presence of phosphatase substrates and stains, intensely stained precipitates are formed on his bacterial component. Such precipitates make the cells become stained and cause the intense pigmentation of the phosphatase positive colonies.


Preoperative and postoperative cytokines in patients with cancer.
Changes in tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and granulocyte macrophage-colony-stimulating factor (GM-CSF) were investigated before and after operation in patients with hepatocellular carcinoma (HCC), metastatic liver carcinoma, and gastrointestinal carcinoma. Serum levels of TNF-alpha, IL-1 alpha, and IL-1 beta were high in patients with liver carcinoma (HCC and metastatic liver carcinoma) before operation in comparison with those of normal controls (P less than 0.01). In patients with gastrointestinal carcinoma, serum levels of cytokines, except those of TNF-alpha, were the same as in patients with liver carcinoma. The level of TNF-alpha in patients with gastrointestinal carcinoma was low compared with that in patients with liver carcinoma. Within 1 day after operation, the peak level of TNF-alpha was observed at 15 hours, IL-1 alpha at 18 hours, IL-1 beta at 21 hours, and IL-6 at 24 hours after operation. Subsequently, these cytokine levels peaked again: TNF-alpha at 48 hours, IL-1 alpha at 72 hours, IL-1 beta at 120 hours, and IL-6 at 168 hours after operation. GM-CSF levels increased gradually after operation. Moreover, in HCC, serum levels of TNF-alpha were high in patients with recurrence compared with those without recurrence (P less than 0.01). The difference in IL-1 alpha and IL-1 beta levels between patients with recurrence and those without recurrence can be regarded as significant (P less than 0.01). These results suggest that TNF-alpha, IL-1, IL-6, and GM-CSF may play an important role in the pathogenesis of cancers; TNF-alpha may be especially important as a tumor marker in HCC and metastatic liver carcinoma.


Speedup of quantum evolution of multiqubit entanglement states.
As is well known, quantum speed limit time (QSLT) can be used to characterize the maximal speed of evolution of quantum systems. We mainly investigate the QSLT of generalized N-qubit GHZ-type states and W-type states in the amplitude-damping channels. It is shown that, in the case N qubits coupled with independent noise channels, the QSLT of the entangled GHZ-type state is closely related to the number of qubits in the small-scale system. And the larger entanglement of GHZ-type states can lead to the shorter QSLT of the evolution process. However, the QSLT of the W-type states are independent of the number of qubits and the initial entanglement. Furthermore, by considering only M qubits among the N-qubit system respectively interacting with their own noise channels, QSLTs for these two types states are shorter than in the case N qubits coupled with independent noise channels. We therefore reach the interesting result that the potential speedup of quantum evolution of a given N-qubit GHZ-type state or W-type state can be realized in the case the number of the applied noise channels satisfying M < N.


Statistically controlled identification of differentially expressed genes in one-to-one cell line comparisons of the CMAP database for drug repositioning.
The Connectivity Map (CMAP) database, an important public data source for drug repositioning, archives gene expression profiles from cancer cell lines treated with and without bioactive small molecules. However, there are only one or two technical replicates for each cell line under one treatment condition. For such small-scale data, current fold-changes-based methods lack statistical control in identifying differentially expressed genes (DEGs) in treated cells. Especially, one-to-one comparison may result in too many drug-irrelevant DEGs due to random experimental factors. To tackle this problem, CMAP adopts a pattern-matching strategy to build "connection" between disease signatures and gene expression changes associated with drug treatments. However, many drug-irrelevant genes may blur the "connection" if all the genes are used instead of pre-selected DEGs induced by drug treatments. We applied OneComp, a customized version of RankComp, to identify DEGs in such small-scale cell line datasets. For a cell line, a list of gene pairs with stable relative expression orderings (REOs) were identified in a large collection of control cell samples measured in different experiments and they formed the background stable REOs. When applying OneComp to a small-scale cell line dataset, the background stable REOs were customized by filtering out the gene pairs with reversal REOs in the control samples of the analyzed dataset. In simulated data, the consistency scores of overlapping genes between DEGs identified by OneComp and SAM were all higher than 99%, while the consistency score of the DEGs solely identified by OneComp was 96.85% according to the observed expression difference method. The usefulness of OneComp was exemplified in drug repositioning by identifying phenformin and metformin related genes using small-scale cell line datasets which helped to support them as a potential anti-tumor drug for non-small-cell lung carcinoma, while the pattern-matching strategy adopted by CMAP missed the two connections. The implementation of OneComp is available at https://github.com/pathint/reoa . OneComp performed well in both the simulated and real data. It is useful in drug repositioning studies by helping to find hidden "connections" between drugs and diseases.


Multidimensional pain assessment in premature neonates: a pilot study.
To describe the physiologic and behavioral responses of premature neonates to a painful stimulus. Descriptive. Secondary-level neonatal unit in a large metropolitan university teaching hospital. Forty neonates between 32 and 34 weeks' postconceptual age and less than 5 days' postnatal age. Physiologic (heart rate, oxygen saturation, and intracranial pressure) and behavioral (facial expression and cry) outcomes observed during a routine heel stick. Physiologic responses were significant, but were not specific to pain. Behavioral responses were more promising and indicated that premature neonates were capable of responding in a manner similar to full-term neonates. Premature neonates are capable of expressing their pain in a manner similar to healthy, full-term neonates. Factors that alter this response were not clearly delineated. Further research is needed to determine more precise patterns of response in this age group.


Early pathologic findings and long-term improvement in anti-Ma2-associated encephalitis.
A 67-year-old man sequentially developed anti-Ma2-associated paraneoplastic encephalitis (PNE) and contralateral herpes simplex encephalitis (HSE). Brain biopsy 1 month before HSE revealed extensive infiltrates of T cells, B cells, and plasma cells. Most T cells expressed the cytotoxic granule-associated protein TIA-1 and the membranolytic protein granzyme-B. Although recovery was thought to be unlikely, treatment of the PNE with corticosteroids and resection of the associated lung cancer resulted in dramatic improvement for 21 months.


Dinophysis Ehrenberg (Dinophyceae) in Southern Chile harbours red cryptophyte plastids from Rhodomonas/Storeatula clade.
Photosynthetic species of the dinoflagellate genus Dinophysis are known to retain temporary cryptophyte plastids of the Teleaulax/Plagioselmis/Geminigera clade after feeding the ciliate Mesodinium rubrum. In the present study, partial plastid 23S rDNA sequences were retrieved in Southern Chilean waters from oceanic (Los Lagos region), and fjord systems (Aysén region), in single cells of Dinophysis and accompanying organisms (the heliozoan Actinophrys cf. sol and tintinnid ciliates), identified by means of morphological discrimination under the light microscope. All plastid 23S rDNA sequences (n = 23) from Dinophysis spp. (Dinophysis acuta, D. caudata, D. tripos and D. subcircularis) belonged to cryptophytes from clade V (Rhinomonas, Rhodomonas and Storeatula), although they could not be identified at genus level. Moreover, five plastid sequences obtained from heliozoans (Actinophryida, tentatively identified as Actinophrys cf. sol), and tintinnid ciliates, grouped together with those cryptophyte sequences. In contrast, two additional sequences from tintinnids belonged to other taxa (chlorophytes and cyanobacteria). Overall, the present study represents the first time that red cryptophyte plastids outside of the Teleaulax/Plagioselmis/Geminigera clade dominate in wild photosynthetic Dinophysis spp. These findings suggest that either Dinophysis spp. are able to feed on other ciliate prey than Mesodinium and/or that cryptophyte plastids from clade V prevail in members of the M. rubrum species complex in the studied area.