Reproducibility of cardiac stroke volume estimated by Doppler echocardiography.
Doppler echocardiography was used to measure cardiac stroke volume in 10 patients with coronary artery disease who were treated with cardioactive drugs. Stroke volume estimates were determined at the aortic orifice by multiplying area by systolic velocity integral measured both from the suprasternal and the apical approach. Recordings were done independently by 2 experienced observers on the same day and repeated once after 1 to 21 days. Analysis of variance showed that no systematic differences were introduced by the 2 observers and Doppler approaches or by measuring on different days. The coefficient of variation between any pair of measurements in each patient was 9%. This variability is probably a result of the method or spontaneous fluctuations of the stroke volume and not of the varying recording conditions. The ultrasonic method detects day-to-day changes of cardiac stroke volume larger than 20% with a probability greater than 0.95.


Can coronary artery anomalies be detected on CT calcium scoring studies?
To determine whether coronary artery anomalies can be detected on noncontrast computed tomography (CT) coronary artery calcium scoring (CCS) studies. A total of 126 patients (mean age 62 years; 35 women) underwent noncontrast CCS and contrast enhanced coronary CT angiography (cCTA). Thirty-three patients were diagnosed with a coronary anomaly on cCTA, whereas coronary anomalies were excluded in 93. Two observers (reader 1 [R1] and reader 2 [R2]), blinded to patient information independently evaluated each CCS study for: 1) visibility of coronary artery origins, 2) detection of coronary anomalies, and 3) benign or malignant (ie, interarterial) course. Using cCTA as the reference standard, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CCS studies for detecting coronary anomalies were calculated. Of the 33 coronary anomalies, 16 were benign and 17 malignant. Based on noncontrast CCS studies, R1 and R2 correctly identified the left main origin in 123/126 (97.6%) and 121/126 (96%) patients; the left anterior descending origin in 125/126 (99.2%) and 122/126 (96.8%); the circumflex origin in 120/126 (95.2%) and 105/126 (83.3%); and the right coronary artery origin in 117/126 (92.9%) and 103/126 (81.7%), respectively. R1 and R2 identified 34 and 27 coronary anomalies and classified 19 and 15 as malignant, respectively. Interobserver reproducibility for detection of coronary anomalies was good (k = 0.76). Interobserver agreement for detection of malignant variants was even stronger (k = 0.80). On average, coronary artery anomalies were diagnosed with 85.2% sensitivity, 96.4% specificity, 90.5% PPV, and 94.1% NPV on noncontrast CCS studies. Benign and malignant coronary artery anomalies can be detected with relatively high accuracy on noncontrast-enhanced CCS studies. CCS studies should be reviewed for signs of coronary artery anomalies in order to identify malignant variants with possible impact on patient management.


Improved enzymatic hydrolysis yield of rice straw using electron beam irradiation pretreatment.
Rice straw was irradiated using an electron beam at currents and then hydrolyzed with cellulase and beta-glucosidase to produce glucose. The pretreatment by electron beam irradiation (EBI) was found to significantly increase the enzyme digestibility of rice straw. Specifically, when rice straw that was pretreated by EBI at 80 kGy at 0.12 mA and 1 MeV was hydrolyzed with 60 FPU of cellulase and 30 CBU of beta-glucosidase, the glucose yield after 132 h of hydrolysis was 52.1% of theoretical maximum. This value was significantly higher than the 22.6% that was obtained when untreated rice straw was used. In addition, SEM analysis of pretreated rice straw revealed that EBI caused apparent damage to the surface of the rice straw. Furthermore, EBI pretreatment was found to increase the crystalline portion of the rice straw. Finally, the crystallinity and enzyme digestibility were found to be strongly correlated between rice straw samples that were pretreated by EBI under different conditions.


Liver subcellular fatty acid profiles of chicks fed diets containing hydrogenated fats and varying linoleate levels.
Day-old male broiler chickens were fed semipurified diets containing 5% lipid from one of four different lipid sources: corn oil (CO), partially hydrogenated soybean oil (HSBO), a spent restaurant grease (SRG) and a purified mixture of triolein, tripalmitin and tristearin (OPS). Diets CO and HSBO contained adequate amounts of linoleic acid, but diets SRG and OPS were deficient in linoleate. In addition, SRG and HSBO contained trans isomers of 16:1 and 18:1. The diets were fed for 3 wk to determine the effects of low linoleate levels and trans isomers on fatty acid profiles in liver microsomes, mitochondria and cytosol. Chicks fed HSBO had the highest body weights, while those fed SRG and OPS had the lowest. The incidence and severity of dermatitis were similar for all treatments. The proportions of linoleate and arachidonate in lipids from liver subcellular fractions were reduced significantly in chicks fed OPS and SRG; however, levels of 20:3 omega 9 were not increased. Feeding HSBO, which is high in both linoleate and linolenate, resulted in higher levels of 18:3 omega 3 and 20:5 omega 3 in liver subcellular fractions and lower levels of 20:4 omega 6 than those seen in chicks fed CO. The isomeric forms of 18:1 present in the partially hydrogenated fats (HSBO and SRG) appeared to be incorporated into the lipids of liver fractions. The results of this study show that dietary lipids influence fatty acid profiles of chick liver microsomes, mitochondria and cytosol. Decreases in linoleate and arachidonate in these organelles occur before overt essential fatty acid (EFA), deficiency signs in chicks fed EFA-deficient diets.


The usefulness, in pharmacological classification, of complementary pattern-recognition techniques and structure modelling as afforded by the iterative collation of multiple-trial data in data banks.
In this emerging information age no significant limits can be envisaged to the immense resources of knowledge that pharmacological sciences can draw upon by systematically applying multivariate pattern-recognition techniques to those data banks which can be organized internationally with better standardization of descriptors, i.e. by parametrizing observations and evaluating monitoring in experimental, biological assays, clinical trials and postmarketing surveillance. Even conventionally or habitually adopted references and communalities such as traditional drug profiles and receptor models may be iteratively re-checked and suitably adapted so as to take account of more adequate, up-to-date analytical techniques, fresh biological ideas and new advances in terms of physiological refinements. An attempt may also be made to modify the chemicophysical relationships and patterns currently traced on the basis of what are held to be quantitative structure-activity oversimplifications. The present paper focuses upon specifying a number of standardization criteria in conventional assays and upon submitting multiple biological features to monitoring; in addition, it gives some picture of the new trends the approach can offer and draws attention to the more relevant, innovative literature references.


Enhanced model protein adsorption of nanoparticulate hydroxyapatite thin films on silk sericin and fibroin surfaces.
Hydroxyapatite coated metallic implants favorably combine the required biocompatibility with the mechanical properties. As an alternative to the industrial coating method of plasma spraying with inherently potential deleterious effects, sol-gel methods have attracted much attention. In this study, the effects of intermediate silk fibroin and silk sericin layers on the protein adsorption capacity of hydroxyapatite films formed by a particulate sol-gel method were determined experimentally. The preparation of the layered silk protein/hydroxyapatite structures on glass substrates, and the effects of the underlying silk proteins on the topography of the hydroxyapatite coatings were described. The topography of the hydroxyapatite layer fabricated on the silk sericin was such that the hydroxyapatite particles were oriented forming an oriented crystalline surface. The model protein (bovine serum albumin) adsorption increased to 2.62 µg/cm2 on the latter surface as compared to 1.37 µg/cm2 of hydroxyapatite on glass without an intermediate silk sericin layer. The BSA adsorption on glass (blank), glass/c-HAp, glass/m-HAp, glass/sericin/c-HAp, and glass/sericin/m-HAp substrates, reported as decrease in BSA concentration versus contact time.


Li+ enhances GABAergic inputs to granule cells in the rat hippocampal dentate gyrus.
Defects in GABAergic interneurons are thought to be involved in the pathophysiology of bipolar disorder, and Li+ has been used as a primary therapeutic agent in the treatment. We used the patch clamp technique to investigate whether Li+ affects on spontaneous GABAergic synaptic inputs to granule cells (GCs) in hippocampal dentate gyrus. Extracellularly applied Li+ (25 mM) markedly increased the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs), an effect completely blocked by picrotoxin or bicuculline. Li+ increased sIPSCs frequency in the presence of tetrodotoxin (TTX), but to a lesser extent than its absence. Li+ caused no change in the cumulative amplitude distribution of miniature IPSCs, indicating that a presynaptic mechanism is involved. When TTX was added in the presence of Li+, large-amplitude sIPSCs (>30 pA) were abolished specifically with no effect on small-amplitude sIPSCs (<20 pA). Intracellular Li+ (6 mM) applied via the patch pipette depolarized the resting membrane potential in fast-spiking interneurons, resulting in an increase in spontaneous action potential (AP) firing. This change, however, was not observed in GCs. These results suggest that Li(+)-induced spontaneous AP firing in GABAergic interneurons contributes to the increase in GABAergic synaptic inputs to GCs.


Higher reward value of starvation imagery in anorexia nervosa and association with the Val66Met BDNF polymorphism.
Recent studies support the idea that abnormalities of the reward system contribute to onset and maintenance of anorexia nervosa (AN). Next to cues coding for overweight, other research suggest cues triggering the proposed starvation dependence to be pivotally involved in the AN pathogenesis. We assessed the characteristics of the cognitive, emotional and physiologic response toward disease-specific pictures of female body shapes, in adult AN patients compared with healthy control (HC) women. Frequency and amplitude of skin conductance response (SCR) in 71 patients with AN and 20 HC were registered during processing of stimuli of three weight categories (over-, under- and normal weight). We then assessed the role of the Val66Met BDNF polymorphism as a potential intermediate factor. AN patients reported more positive feelings during processing of underweight stimuli and more negative feelings for normal- and overweight stimuli. The SCR showed a group effect (P=0.007), AN patients showing overall higher frequency of the response. SCR within patients was more frequent during processing of underweight stimuli compared with normal- and overweight stimuli. The Met allele of the BDNF gene was not more frequent in patients compared with controls, but was associated to an increased frequency of SCR (P=0.008) in response to cues for starvation. A higher positive value of starvation, rather than more negative one of overweight, might more accurately define females with AN. The Met allele of the BDNF gene could partly mediate the higher reward value of starvation observed in AN.


[Bolton indices in Cl II/1, Cl II/2 and Cl I anomalies with frontal crowding].
The Bolton indices in Kl II/1, Kl II/2 and Kl I anomalies with frontal crowding are examined.


Dynamic nuclear polarisation of 1H in Gd-doped In(OH)3.
Dynamic nuclear polarisation (DNP) of solids doped with high-spin metal ions, such as Gd3+, is a useful strategy to enhance the nuclear magnetic resonance (NMR) sensitivity for these samples. Spin diffusion can relay polarisation throughout a sample, which is most effective for dense 1H networks, while the efficiency of DNP using Gd3+ depends on the symmetry of the metal site. Here, we investigate cubic In(OH)3 as a high-symmetry, proton-containing material for endogenous Gd DNP. A 1H enhancement of up to 9 is demonstrated and harnessed to measure the 17O spectrum at natural abundance. The enhancement is interpreted in terms of clustering of the Gd3+ dopants and the local reduction in symmetry of the metal site induced by proton disorder, as demonstrated by quadrupolar 115In NMR. This is the first example of 1H DNP using Gd3+ dopants in an inorganic solid.


Occupational co-exposure to biomechanical factors and neurotoxic chemicals in a representative sample of French employees.
Musculoskeletal disorders, mainly carpal tunnel syndrome, represent a leading cause of compensation claims of workers worldwide. Despite this, and the fact that occupational exposures to biomechanical factors and neurotoxic chemicals have been individually associated with peripheral nerve damage, the prevalence of occupational co-exposure to biomechanical factors and neurotoxic chemicals has rarely been explored. Therefore, our aim was to assess the prevalence of occupational co-exposure to biomechanical factors and neurotoxic chemicals in a national representative sample of the French working population. The study was based on the French representative cross-sectional survey SUMER 2010. A total of 47 983 employees who had worked in their current job for at least one year were included. Occupational exposure to biomechanical factors and neurotoxic chemicals within the previous week of work were assessed using a questionnaire during face-to-face interviews with occupational physicians. Approximately 5% of male employees and 1% of female employees were co-exposed to biomechanical factors and neurotoxic chemicals. This prevalence was up to 10% among male blue-collar workers and 13%, 8%, and 6%, respectively, among male employees in the construction, agriculture, and industry sectors. Male employees under 30 years old, in apprenticeships, and working in small companies were more co-exposed to biomechanical factors and neurotoxic chemicals than their counterparts. Occupational co-exposure to biomechanical factors and neurotoxic chemicals was observed in a significant proportion of French male employees, suggesting that further studies are required to investigate its potential adverse effects on peripheral neuropathies.


Eyes for Ears: Usage and Efficacy of a Podcast for Ophthalmic Education.
To characterize listenership and perceived educational impact of the ophthalmic podcast "Eyes for Ears". A cross-sectional, internet-distributed, 9-question Qualtrics survey was made available to podcast listeners. Listenership metrics were analyzed from the podcast host platform. From January 10, 2019 to September 2, 2021, the podcast was downloaded over 422,000 times, averaging about 4442 downloads per episode. 209 Qualtrics survey responses were analyzed from podcast listeners with backgrounds in eye care including medical students, residents, fellows, clinicians and technicians. The majority were residents (60.3%), representative of the target audience of the podcast. Listeners reported using the podcast while commuting (81.3%), felt it increased the time they could spend on self-care (63.2%), and thought it improved their fund of knowledge (99.0%). Respondents recalled feeling better prepared for the OKAP or written boards after using this podcast (before median = 50/100 on Likert Scale, IQR 30-65 vs median = 70/100, IQR 56-81, p <0.001). Respondents identified question banks as the most helpful for OKAP studying, followed by podcasts. Podcasts were preferred over articles and lectures in terms of helpfulness (p < 0.001). The Eyes for Ears podcast has achieved a robust international audience. The surveyed audience felt the podcast was useful for their education and well-being.


Supine headache and papilledema: A case and review of cerebral venous sinus thrombosis.
Cerebral venous sinus thrombosis (CVST) should be on the differential for intracranial hypertension, and the preferred diagnostic tests are CT venogram or MR venography. Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke and is on the differential for intracranial hypertension. Non-contrast head CT is often normal. CT venogram or MR venography are the preferred diagnostic tests, as was required in our patient. We review the presentation, diagnosis, and management of CVST.


Discrete quinolinic acid lesions of the rat prelimbic medial prefrontal cortex affect cocaine- and MK-801-, but not morphine- and amphetamine-induced reward and psychomotor activation as measured with the place preference conditioning paradigm.
As a part of the mesocorticolimbic system, the medial prefrontal cortex (mPFC) is thought to participate in the regulation of locomotor activity, motivation and reward. The mPFC consists of at least three different subareas. In previous lesion studies examining this region usually large parts of the mPFC were destroyed, with little discrimination between the different subareas. Therefore, this study was designed to selectively lesion the prelimbic area of the mPFC using a relatively low dose of quinolinic acid. In a conditioned place preference (CPP) experiment, lesioned and control animals were treated with cocaine (15 mg/kg), amphetamine (4 mg/kg), morphine (10 mg/kg) or MK-801 (0.3 mg/kg) to induce CPP. The lesion blocked the development of CPP only in animals receiving cocaine, but not in animals receiving amphetamine or morphine. MK-801 failed to produce a CPP in both lesioned and unlesioned animals. During the conditioning experiment, the acute locomotor response to the different drugs was also measured. Only the response (in terms of locomotion and rearing) to cocaine and MK-801 was reduced to a significant extent by the lesion, while the response to amphetamine and morphine was not affected. Also, the lesions did not cause any changes in the spontaneous activity of the animals when tested without drug. These results show that even small lesions of the prelimbic subarea of the mPFC are sufficient to produce behavioral effects. However, these are apparent only when the animals are challenged with cocaine or MK-801, but not with amphetamine or morphine, or when drug-free. This suggests that the mPFC might have a special role in mediating cocaine and MK-801 effects.


Evolution of cadmium resistance in Daphnia magna.
A diverse laboratory population of Daphnia magna Straus was established by combining individuals from eight sources. Artificial selection for increased resistance to the acute toxic effects of cadmium was performed, and after eight generations, the average median effective concentration increased from 61 to 180 microg/L. No differences in life span, offspring production, time to first brood, number of offspring in the first brood, or intrinsic rate of population increase (r) were observed between the cadmium-adapted population and the controls under ideal conditions or under conditions of temperature or feeding ration stress, but cadmium-adapted daphnids were smaller. Control and cadmium-adapted populations were equally sensitive to copper and malathion, but the cadmium-adapted population was less sensitive to lead and more sensitive to phenol. Analysis of amplified fragment-length polymorphisms indicated a significant decrease in genetic diversity in the cadmium-adapted population. Although the evolved cadmium resistance would allow adapted populations to exist in areas where cadmium concentrations would be toxic to unadapted populations, the decreased genetic diversity, smaller size, and increased sensitivity to at least one other toxicant could reduce the probability of long-term survival even in the absence of future cadmium exposure.


Microbial Communities of the Gut and Nest of the Humus- and Litter-Feeding Termite Procornitermes araujoi (Syntermitinae).
The evolution of the symbiotic association with microbes allowed termites to decompose ingested lignocellulose from plant-derived substrates, including herbivore dung and soil humus. Representatives of the Syntermitinae (Termitidae) range in their feeding habits from wood and litter-feeding to humus-feeding species. However, only limited information is available about their feeding ecology and associated microbial communities. Here we conducted a study of the microbial communities associated to the termite Procornitermes araujoi using Illumina sequencing of the 16S and ITS rRNA genes. This species has been previously included in different feeding guilds. However, most aspects of its feeding ecology are unknown, especially those associated to its symbiotic microbiota. Our results showed that the microbial communities of termite guts and nest substrates of P. araujoi differed significantly for bacteria and fungi. Firmicutes dominated the bacterial gut community of both workers and soldiers, whereas Actinobacteria was found in higher prevalence in the nest walls. Sordariomycetes was the most abundant fungal class in both gut and nest samples and distinguish P. araujoi from the grass/litter feeding Cornitermes cumulans. Our results also showed that diversity of gut bacteria were higher in P. araujoi and Silvestritermes euamignathus than in the grass/litter feeders (C. cumulans and Syntermes dirus), that could indicate an adaptation of the microbial community of polyphagous termites to the higher complexity of their diets.


Search for alpha 1-adrenoceptor subtypes selective antagonists: design, synthesis and biological activity of cystazosin, an alpha 1D-adrenoceptor antagonist.
Two novel quinazolines (2 and 3) related to both prazosin and its open analogue 1 were synthesized, and their biological profile at alpha 1-adrenoceptor subtypes was assessed by functional assays in rat isolated tissues, namely prostatic vas deferens (alpha 1A), spleen (alpha 1B) and aorta (alpha 1D). Furthermore, the binding profile of 3 was assessed at native alpha 2 and D2 receptors, and cloned human 5-HT1A receptors, in comparison to prazosin, (+)-cyclazosin, 1 and BMY 7383. It turned out that the cystamine-bearing quinazoline 3 (cystazosin) has a reversed affinity profile relative to (+)-cyclazosin owing to a higher affinity for alpha 1D-adrenoceptors and a significantly lower affinity for the alpha 1A and alpha 1B subtypes. Furthermore, in comparison to BMY 7378, cystazosin (3) displays a much better specificity profile since it has lower affinity for D2 and 5-HT1A receptors.


Release kinetics of platelet-derived and plasma-derived growth factors from autologous plasma rich in growth factors.
Many studies have evaluated the biological effects of platelet rich plasma reporting the final outcomes on cell and tissues. However, few studies have dealt with the kinetics of growth factor delivery by plasma rich in growth factors. Venous blood was obtained from three healthy volunteers and processed with PRGF-Endoret technology to prepare autologous plasma rich in growth factors. The gel-like fibrin scaffolds were then incubated in triplicate, in a cell culture medium to monitor the release of PDGF-AB, VEGF, HGF and IGF-I during 8 days of incubation. A leukocyte-platelet rich plasma was prepared employing the same technology and the concentrations of growth factors and interleukin-1β were determined after 24h of incubation. After each period, the medium was collected, fibrin clot was destroyed and the supernatants were stored at -80°C until analysis. The growth factor delivery is diffusion controlled with a rapid initial release by 30% of the bioactive content after 1h of incubation and a steady state release when almost 70% of the growth factor content has been delivered. Autologous fibrin matrix retained almost 30% of the amount of the growth factors after 8 days of incubation. The addition of leukocytes to the formula of platelet rich plasma did not increase the concentration of the growth factors, while it drastically increased the presence of pro-inflammatory IL-1β. Further studies employing an in vitro inflammatory model would be interesting to study the difference in growth factors and pro-inflammatory cytokines between leukocyte-free and leukocyte-rich platelet rich plasma.


Efficacy of albendazole and levamisole against gastrointestinal nematodes of sheep and goats in Morogoro, Tanzania.
A study was conducted to determine the efficacy of albendazole after it had been withdrawn from use due to the development of resistant strains of nematodes about ten years ago. The study also aimed to determine the present efficacy of levamisole, which had been recommended to replace albendazole. On one farm, the sheep and goats were divided into two groups, one group of each serving as the untreated control, while the other was treated with levamisole. The sheep on the other farm were divided into three groups, one serving as the untreated control group, the second being treated with levamisole and the third being treated with albendazole. Faecal samples were collected one day before treatment, and again 10 days after treatment. Anthelmintic efficacy was determined by the faecal egg count reduction test. Ten days after treatment, the sheep treated with levamisole on the first farm had a 98% reduction in faecal egg count, with a 95% confidence limit of 76%. The goats on the same farm had a 97% reduction in faecal egg count, with a 95% lower confidence limit of 81%. At the second farm, 10 days after treatment, sheep treated with levamisole had a 99.4% reduction in faecal egg count, with a 95% lower confidence limit of 88.9%, whereas the sheep treated with albendazole only had a 59.4% reduction in faecal egg count, with a 95% lower confidence limit of -19.6%. The study indicated that the gastrointestinal nematodes of sheep at the Department of Animal Science and Production farm were still resistant to albendazole about ten years after this anthelmintic had been withdrawn from use. A reduced efficacy of levamisole was suspected.


Basal dendrites of granule cells are normal features of the fetal and adult dentate gyrus of both monkey and human hippocampal formations.
The aim of this study was to analyze the granule cell population of the dentate gyrus both in healthy rhesus monkeys and in humans free of mental and neurological disorders. Brains of neonatal and adult rhesus monkeys as well as brains of fetal, neonatal and adult humans were impregnated with Golgi methods. The results show that a significant population of granule cells have basal dendrites in primates. Some basal dendrites curve up into the molecular layer where they have similar morphology as the apical dendrites. In contrast, other basal dendrites protrude into the hilus and they are shorter, thinner and have only a few side branches. The frequency of granule cells with basal dendrites in the human dentate gyrus is twice as much as that of the rhesus monkey. Most of these human granule cells have their basal dendrites in the hilus. This observation confirms the fact that discrepancies occur in the normal morphology of individual neurons between the rodent and primate hippocampal formations. The results indicate that basal dendrites of granule cells are not pathological as previously suggested.


Ultrasound-guided hydrostatic reduction of intussusception: comparison of success rates between subspecialized pediatric radiologists and non-pediatric radiologists or radiology residents.
Ileocolic intussusception is the most common cause of intestinal obstruction in children under two years of age. Treatment in most cases is radiologically guided reduction. In Slovenia, ultrasound (US)-guided hydrostatic reduction is currently the standard of care. The purpose of this study was to compare the success rate of US-guided hydrostatic reduction when performed by subspecialty-trained pediatric radiologists, non-pediatric radiologists, or radiology residents. We retrospectively analyzed medical records of patients with ileocolic intussusception who underwent US-guided hydrostatic intussusception reduction at University Medical Centre Ljubljana between January 2012 and December 2022 (n = 101). During regular daily working hours, the reduction was performed by pediatric radiologists. After hours (evenings and overnight), pediatric radiologists, non-pediatric radiologists, or radiology residents performed the reduction procedure. Patients were divided into three groups based on the operator performing the procedure. Data was analyzed using the chi-square test. Pediatric radiologists had thirty-seven (75.5%) successful first attempts, non-pediatric radiologists had nineteen (76.0%), and radiology residents had twenty (74.1%). There was no statistically significant difference in the success rate of ileocolic intussusception reduction depending on the operator who performed the procedure (p = 0.98). No perforation was observed in either group during the reduction attempts. Conclusion: Our results demonstrate that US-guided hydrostatic reduction is a reliable and safe procedure that achieves good results even in the hands of less experienced, however appropriately trained, radiologists. The results should encourage more medical centers to consider the implementation of US-guided hydrostatic reduction of ileocolic intussusception. What is Known: • US-guided hydrostatic reduction is a well-established method of treatment for ileocolic intussusception in children. • The results regarding the influence of operator's experience with the procedure on its success rate are scarce and contradictory. What is New: • US-guided hydrostatic intussusception reduction is a reliable and safe technique that achieves similar success rates when performed by experienced subspecialized pediatric radiologists or less experienced but trained operators such as non-pediatric radiologists and radiology residents. • The implementation of US-guided hydrostatic reduction in general hospitals without subspecialized pediatric radiologists could improve patient care by increasing access to radiologically guided reduction and simultaneously decreasing the time to reduction attempts.


Inhibition of mandelate racemase by the substrate-intermediate-product analogue 1,1-diphenyl-1-hydroxymethylphosphonate.
Mandelate racemase has been studied as a paradigm for enzyme-catalyzed abstraction of a proton from carbon acids with relatively high pKa values. 1,1-Diphenyl-1-hydroxymethylphosphonate is a substrate-intermediate-product analogue and is a modest competitive inhibitor of the enzyme (Ki=1.41+/-0.09 mM), suggesting that simultaneous binding of the two phenyl groups obviates mimicry of the aci-carboxylate function of the intermediate by the phosphonate group.


Identification of mutations in the prostaglandin transporter gene SLCO2A1 and phenotypic comparison between two subtypes of primary hypertrophic osteoarthropathy (PHO): A single-center study.
Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis, and pachydermia. Based on two causative genes, hydroxyprostaglandin dehydrogenase (HPGD) and solute carrier organic anion transporter family member 2A1 (SLCO2A1), PHO is categorized into two subtypes: hypertrophic osteoarthropathy, primary, autosomal recessive 1 (PHOAR1) and hypertrophic osteoarthropathy, primary, autosomal recessive 2 (PHOAR2). In this study, we summarized the clinical manifestations and analyzed SLCO2A1 gene in 23 PHOAR2 patients in our center. As a result, 18 patients displayed complete phenotypes of PHO with digital clubbing, periostosis, and pachydermia. 29 mutations were found in total, and 22 of them were novel mutations including 13 missense, three nonsense, four deletion, one frame-shift and one splicing site mutations. Compared with nine PHOAR1 patients we previously reported, PHO patients with SLCO2A1 mutations were all male and presented with a later onset age. Peptic ulcers and myelofibrosis occurred only in PHOAR2 patients. The urinary level of prostaglandin E2 metabolite (PGEM) is significantly higher in PHOAR2 patients than that in PHOAR1 group. In conclusion, this study was the largest cohort to date to summarize PHOAR2 patients and to assess the phenotypic difference between two subtypes of PHO. The difference of urinary PGEM concentration between two subtypes is helpful for the differential diagnosis of PHO.


Monotherapy with mirabegron had a better tolerance than the anticholinergic agents on overactive bladder: A systematic review and meta-analysis.
We conducted this meta-analysis to explore the tolerance of monotherapy with mirabegron (50 mg) on an overactive bladder, compared with a common dosage of anticholinergic agents. A comprehensive search for all randomized controlled trials that evaluated the safety of mirabegron and anticholinergic agents on overactive bladder was performed, and we searched the Cochrane Central Register of Controlled trials databases, Pubmed, Embase, and relevant trials from 2013.02 to 2019.10. Eight studies included 5500 patients with treatment of monotherapy on overactive bladder were identified. The total number of treatment-emergent adverse events had no significantly difference between two monotherapies (RR = 0.88 95%CI: 0.76-1.01; P = .08); however, patients would have a better tolerance with mirabegron (50 mg) in adverse events of dry mouth (RR = 0.42; 95%CI: 0.33-0.53; P < .01) and tachycardia (RR = 0.52; 95%CI: 0.29-0.94; P = .03); and there were no significant differences between two groups in hypertension (RR = 1.02; 95%CI: 0.80-1.30; P = .90), constipation (RR = 0.91; 95%CI: 0.65-1.26; P = 0.57), blurred vision (RR = 1.03; 95%CI: 0.60-1.77; P = 0.92), and urinary tract infection (RR = 0.90; 95%CI: 0.70-1.16; P = .41). Treatment-emergent adverse events in patients with overactive bladder who underwent monotherapy of mirabegron (50 mg) or the anticholinergic agents had no significant differences, but mirabegron has a better tolerance in the aspect of dry mouth and tachycardia.


Immunoreactive fucosylceramide as a B-cell differentiation marker.
The reactivity of PC47H, a monoclonal antibody (mAb) directed against fucosylceramide, with cells of lymphoid lineage was examined. Immunoreactive fucosylceramide (FC) was recognized only in pokeweed mitogen (PWM)-stimulated B blasts, plasma cells and germinal center cells. mAb PC47H did not react with T cells at different stages or with peripheral blood B cells. Furthermore, FC was expressed abundantly in blastic cells of B-cell lymphoma, multiple lymphoma and myeloma cell lines KMS-12-BM and KMS-12-PE. In other words, FC was expressed more strongly in mature than in immature B cells. Immunoelectron microscopy showed that FC was located in the plasma membrane and rough endoplasmic reticulum. mAb PC47H can therefore be used as a unique B-cell differentiation marker for study of B-cell activation and differentiation and clonal analysis of lymphoid malignancies.


An improved syncytia infectivity assay for the bovine leukemia virus.
Several factors that influence the sensitivity of the syncytia infectivity assay for the bovine leukemia virus (BLV) and BLV-infected lymphocytes have been examined. The use of early-passage indicator bovine embryonic spleen (BESP) cells and their pretreatment with diethylamino-ethyl-dextran (DEAE-D) was essential for optimal sensitivity. Polybrene was less effective than DEAE-D. The combination of DEAE-D and polybrene was more effective than DEAE-D alone when BLV-infected leukocytes were used as the inoculum, but not when the inoculum was a cell-free BLV preparation. Using BESP cell passages 4 to 11 as indicators, reproducible titers were obtained when aliquots of the same virus stock were assayed at different times after freezer storage. When assaying peripheral blood lymphocytes from infected cattle, optimal syncytia responses were observed consistently by inoculating 5 X 10(6) viable lymphocytes per 60-mm Falcon dish. Centrifugation of peripheral blood leukocytes from BLV-infected cattle in discontinuous bovine serum albumin gradients can be used to separate a subpopulation of infected lymphocytes. Use of this subpopulation as the inoculum, rather than unseparated buffy-coat leukocytes, greatly increases the sensitivity of the syncytia infectivity assay.


Nurses' and nursing students' reasons for entering the profession: content analysis of open-ended questions.
Global nursing shortages require effective recruitment strategies and understanding of individuals' motivations to enter the profession. These can be complex and bound by numerous factors such as gender and culture. While much research around this has been conducted, little has been undertaken in non-Western cultures where motivations could be different. To explore Indonesian nurses' and nursing students' motivations for entering the nursing profession. Online survey with closed and open-ended questions drawn from two different studies. This paper reports findings from one similar open-ended question. As part of two larger surveys, nurses from 13 hospitals across one private health care group and nursing students with clinical experienced enrolled in a baccalaureate nursing program in Indonesia were asked the question, Why do you want to be a nurse? Responses were translated into English and back-translated into Indonesian prior to being subjected to summative content analysis. In total, 1351 nurses and 400 students provided responses to the question, representing 98.72% and 99.70% respectively of those completing the survey. Both groups were primarily influenced by desire to serve others and God, personal calling and influence of family members and others. Nurses identified a desire to work in the health field and with the sick, in a noble and caring profession. Nurses and nursing students were motivated by traditional perspectives on nursing. These should be considered in future recruitment activities. However, more research is needed to understand how these factors influence career choice.


Lipoprotein B37, a naturally occurring lipoprotein containing the amino-terminal portion of apolipoprotein B100, does not bind to the apolipoprotein B,E (low density lipoprotein) receptor.
In 1979, Steinberg and colleagues described a unique kindred with familial hypobetalipoproteinemia (Steinberg, D., Grundy, S. M., Mok, H. Y. I., Turner, J. D., Weinstein, D. B., Brown, W. V., and Albers, J. J. (1979) J. Clin. Invest. 64, 292-301). Recently, we demonstrated the existence of an abnormal species of apolipoprotein (apo-) B, apo-B37 (Mr = 203,000) in nine members of that kindred (Young, S. G., Bertics, S. J., Curtiss, L. K., and Witztum, J. L. (1987) J. Clin. Invest. 79, 1831-1841; Young, S. G., Bertics, S. J., Curtiss, L. K., Dubois, B. W., and Witztum, J. L. (1987) J. Clin. Invest. 79, 1842-1851). Apolipoprotein B37 contains only the amino-terminal portion of apo-B100. In affected individuals most of the apo-B37 is contained in the high density lipoprotein (HDL) fraction (d = 1.063-1.21 g/ml), where it is the principal apolipoprotein in a unique lipoprotein (Lp) particle, Lp-B37, which contains little, if any, apo-A-I. However, the most abundant lipoprotein in the HDL density fraction is a smaller particle, which contains apo-A-I, but no apo-B. The Lp-B37 particles were isolated from the HDL of affected individuals by immunoabsorption of apo-B37. Selected affinity antibodies specific for apo-B37 were used to prepare an anti-apo-B37-Sepharose 4B column. Lipoproteins not bound by the column (unbound HDL fraction) contained apo-A-I, but no apo-B. The Lp-B37, which was eluted from the column with 3 M KI, contained apo-B37 and trace amounts of apo-A-I, but no apo-B100. Over a 4-h period, normal human fibroblasts degraded 10-fold more 125I-low density lipoprotein (LDL) than 125I-Lp-B37. Also, whereas addition of excess unlabeled LDL markedly reduced degradation of 125I-LDL, it did not significantly reduce the degradation of 125I-Lp-B37. Unlabeled Lp-B37 did not inhibit uptake and degradation of 125I-LDL by fibroblasts. These data suggest that the amino-terminal portion of apo-B100, when expressed on a naturally occurring lipoprotein particle, does not contain a functional apo-B,E(LDL) receptor binding domain.


Hepatic falciform ligament artery: angiographic anatomy and clinical importance.
The hepatic falciform ligament artery (HFLA) was evaluated by angiography and also by dissections. Based on the findings, the mechanism of the post-chemoembolization skin rash was studied. A total of 340 liver cirrhosis patients who underwent hepatic artery chemoembolization for hepatocellular carcinoma were reviewed in terms of the angiographic incidence of the HFLA, variations in its origin, and the incidence of skin rash. The HFLA was demonstrated in 26 (7.6%) of the 340 patients on angiography. Two HFLAs were observed in one patient. The origin was the middle hepatic artery (A4) in 16 cases, the superior branch of the middle hepatic artery in three, the inferior branch of the middle hepatic artery in two, the inferior branch of the left hepatic artery (A3) in three, and the confluence of A3 and A4 in three cases. There were no patients who developed post-chemoembolization skin rash. Two cadavers were dissected to investigate the anastomosis between the HFLA and the subcutaneous artery. Two different anastomoses were found: (1) direct and (2) via the ensiform branch of the internal thoracic artery. These were located at the lower and upper part of the falciform ligament, respectively. The distribution of a chemotherapeutic agent through these anastomoses is the likely cause of post-chemoembolization skin rash. If prophylactic embolization of the proximal portion of the HFLA using a metallic coil is performed, the skin rash will be prevented.


The evolution of adaptive immune systems.
A clonally diverse anticipatory repertoire in which each lymphocyte bears a unique antigen receptor is the central feature of the adaptive immune system that evolved in our vertebrate ancestors. The survival advantage gained through adding this type of adaptive immune system to a pre-existing innate immune system led to the evolution of alternative ways for lymphocytes to generate diverse antigen receptors for use in recognizing and repelling pathogen invaders. All jawed vertebrates assemble their antigen-receptor genes through recombinatorial rearrangement of different immunoglobulin or T cell receptor gene segments. The surviving jawless vertebrates, lampreys and hagfish, instead solved the receptor diversification problem by the recombinatorial assembly of leucine-rich-repeat genetic modules to encode variable lymphocyte receptors. The convergent evolution of these remarkably different adaptive immune systems involved innovative genetic modification of innate-immune-system components.


Somato-motor components of the pelvic and pudendal nerves of the female rat.
The efferent innervation of the pelvic and pudendal nerves was characterized in this study by identifying the muscles activated by electrical stimulation of the nerves distal to the point at which they bifurcate from the L6-S1 trunk. Pelvic nerve electrical stimulation produced EMG-monitored contraction of the ipsilateral ilio- and pubococcygeus muscles, which was abolished by cutting one ('muscular') branch of the bifurcated nerve. (This 'muscular' branch receives proprioceptive input activated by tail displacement, whereas the other, 'viscero-cutaneous' branch receives sensory innervation from the midline perineal region.) Pudendal nerve electrical stimulation produced contraction of the coccygeus, external anal sphincter, and ischiocavernosus muscles. Movements of the orifice and wall of the vagina were directly visualized during electrical stimulation of the two nerves. Intravaginal pressure measured by balloon was increased by pelvic nerve stimulation and decreased by pudendal nerve stimulation. Reflexive contraction of the ilio- en pubococcygeus muscles was produced by mechanostimulation of the perineum, clitoral sheath and distal vagina. This response was abolished by gentle cervical mechanostimulation. One implication of this finding is that passage of the fetuses through the cervix during parturition may relax the ilio- and pubococcygeus muscles, thereby facilitating delivery.


NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury.
Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury.


Evaluation of tachykinins and their receptors to determine sensory innervation in the dorsal hoof wall and insertion of the distal sesamoidean impar ligament and deep digital flexor tendon on the distal phalanx in healthy feet of horses.
To localize substance P (SP) and neurokinin A (NKA) and their receptors in the insertion of the distal sesamoidean impar ligament (DSIL), deep digital flexor tendon (DDFT), and dorsal hoof wall of healthy feet of horses. 18 healthy feet from horses. Samples from the dorsal hoof wall and insertion of the DSIL and DDFT of 10 feet were processed for immunocytochemical analysis, using rabbit polyclonal antisera raised against SP and NKA. Tissue sections from 8 feet were incubated with 125-labeled SP to localize tachykinin receptors and their specificity and with control solutions of radioactive SP and excess nonradioactive SP to identify areas of nonspecific binding. Many nerves immunoreactive for SP and NKA were localized to the region of the insertion of the DSIL and DDFT and the accompanying microvasculature and arteriovenous complexes (AVC) as well as to the microvasculature of the dorsal hoof wall. Specific neurokinin 1 receptors were localized over the microvessels and AVC of the insertion zone and small microvessels of the hoof wall. These results document that the microvasculature of the equine foot is richly innervated and has specific receptors for tachykinins. Distributions of these tachykinin receptors on the microvasculature suggest that they form an important vasodilatory mechanism for controlling blood flow through the DSILDDFT insertion and dorsal hoof wall.


Transcription of plasmid DNA in Escherichia coli minicells.
Cellular RNA polymerase in association with plasmid DNA segregates into the minicells of minicell-producing strains. In general, one "plasmid equivalent" of RNA polymerase, reflecting the size of the segregating plasmid DNA and its efficiency of segregation, entered the minicell with the plasmid. The amount of RNA polymerase (measured as the amount of enzyme activity purified from minicells and the rate of RNA synthesis in plasmid-containing minicells), and not the DNA content, appeared to be rate-limiting in plasmid-mediated transcription in minicells. The purified minicell and cellular RNA polymerases showed the same sensitivity to rifampin and streptolydigin; both were associated with sigma factor, although the minicell enzyme appeared to have slightly less than the cellular enzyme. These studies demonstrate that transcription of plasmid DNA in minicells is a function of the efficiency of segregation and the amount of RNA polymerase which enters with the plasmid DNA. Because RNA polymerase is limiting, plasmids with relatively weak promoters for the vector genes should be used when attempting to identify products from inserted foreign DNA.


Information subsystem of the SO4/Cl ratio as database for studying its influence on human health.
General lack of surface waters in the Dalmatian region on one hand (Croatia) and a large profusion and complexity of underground waters circulation, on the other hand, are typical phenomena of Dalmatian Karst region. Underground waters in Dalmatia belong to rift water similar to surface waters considering its hydrochemical and hygienic characteristics. Health care institutions and water authorities have become particularly interested in observing and monitoring water as well as preserving its quality. A relational database has been developed for carrying out chemical analyses expressed by the SO4/Cl ratio since it is necessary to organize and integrate a large number of analytical and ecological health-data. The database can serve as a methodological platform for the study of environmental factors influencing human health. The prototype database consists of data obtained by investigations, which have been conducted by the Water Examination Department of the Public Health Institute of Split Dalmatian County (Croatia) and University of Split Medical School. The database currently contains more than 3000 data.


Development of a dual-luciferase fusion gene as a sensitive marker for site-directed DNA repair strategies.
Several novel techniques have been developed recently for the site-specific repair of DNA as an approach to gene therapy. Correction efficiencies as high as 40% have been reported, well within the range of therapeutic impact for a number of genetic diseases. Unfortunately, many of the model systems in which these methods have been employed typically target genes that are not well suited for analyzing the various techniques. To address this, we have constructed and characterized a dual-luciferase fusion gene as a sensitive marker for optimizing repair strategies. The genes encoding two distinct luciferase proteins were fused so that expression of one luciferase necessitated expression of the other. Engineering a stop codon in the downstream luciferase gene created an ideal tool to study the efficiency of various site-directed DNA repair techniques as one luciferase can act as an internal control while the other is targeted for correction. Fusing two luciferase genes resulted in a single protein that produces two bioluminescent activities in a constant ratio. The utility of this system as a target for site-directed DNA repair research was demonstrated using two of the recently developed gene repair techniques, small fragment homologous replacement and oligonucleotide-mediated repair, to mediate correction and by the ability to detect repair efficiencies of less than 5 x 10(-6) (<1 event in 200000). The ability to rapidly and accurately quantify the amount of correction using the dual-luciferase fusion system will allow the comparison and evaluation of the many factors involved in successful gene repair and lead to the optimization of these techniques, both in cell culture and in whole animals.


Machine Learning for Autistic Spectrum Disorder Risk Screening.
In the modern world of rapidly increasing autistic spectrum disorder case rates, medical costs, societal impact, and long-waiting times from initial screening, there is a need for an easy, early screening of autistic spectrum disorder risk in children. In this paper, a mobile application was developed with these requirements, using machine learning algorithms achieving high performance compared to other applications that use simple rule approaches. A recently published autistic spectrum disorder dataset is used to train the model, containing hundreds of screening data from children in the ages 4 to 11.


Clinical course, imaging, and pathological features of 45 adult and pediatric cases of myelin oligodendrocyte glycoprotein antibody-associated disease.
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described neuroinflammatory demyelinating disease. To better understand the clinical spectrum, risk factors and outcomes in MOGAD. Retrospective cohort study including all subjects harboring anti-MOG antibodies identified in major academic hospitals across the province of Quebec. We identified 45 MOGAD cases. The minimal estimated point-prevalence was 0.52/100 000 in Quebec. Median age at presentation was 32 years (range 1-71) with equal sex ratio. Most frequent ethnic groups were Caucasians and Asians. The most frequent clinical manifestations at onset were optic neuritis (ON), affecting 56% of adults, and acute disseminated encephalomyelitis (ADEM), affecting 33% of children. First MRI was abnormal in 84% of cases. Most CSF samples showed pleocytosis without oligoclonal bands. Two brain biopsies revealed lipid-laden macrophages and reactive astrocytes. Despite steroids, only 38% had fully recovered at 4 weeks after onset. Half of pediatric and two thirds of adult-onset MOGAD subjects experienced relapses. At last follow-up, 69% showed residual deficits, which were moderate to severe in 17% of adults. MOGAD has heterogeneous disease course, and it is not a benign disease for a substantial proportion of adults. Best disease-modifying therapies remain to be determined.


Food availability and shopping channels during the disasters: Has the COVID-19 pandemic changed peoples' online food purchasing behavior?
COVID-19 caused online buying channels to flourish across the globe. However, the extent to which online channels in Pakistan assisted peoples in coping with the pandemic remains unknown. This study aims to examine peoples behavior and perceptions regarding online food purchasing and its impact on different aspects of food security. The data were collected through online surveys of 1067 respondents in Punjab and Sindh provinces during the COVID-19 pandemic. We find that peoples access to food was adversely affected by the pandemic. However, people are increasingly purchasing food online, which has improved their accessibility to food. According to the findings, 62.51% of respondents reported to have changed their perception and behavior regarding online food purchasing. In addition, almost 46.40% of peoples reported that online shopping increased their access to food during the pandemic. Using logit regression, economic analysis shows that education, monthly income, and access to basic necessities such as clean drinking water, better sanitation, and better employment are positively related to online buying behavior. For future disaster situations in Pakistan to mitigate the adverse effects on food security, strengthening and promoting the use of online purchasing channels could be an important policy instrument.


Access to Healthcare Services and Essential Medicines in GREEK Migrant Camps: an Online Cross-Sectional Study.
During the last years, Greece has become the entry point of a high number of migrants and asylum seekers. The aim of this study was to assess the access to selected fields of primary healthcare, to emergency medical care, secondary healthcare and essential medicines among populations living in reception, temporary accommodation, and detention centres (migrant camps) in Greece. An online cross-sectional survey was conducted based on a self-administered questionnaire. Participants included indviduals working or volunteering in migrant camps in Greece. 64 individuals participated in this study. The most common health problem among people residing in migrant camps was mental health conditions. The access to each field of primary healthcare was assessed as minimum to non-existent by most of the participants. 47.2% assessed the access to emergency medical care as minimum/non-satisfactory, while 60.8% assessed the access to secondary healthcare as minimum to non-existent. Most participants assessed the access to all the medicines categories as minimum or moderate. Access to both primary and secondary health was given a lower grade in the East-Aegean islands compared to the mainland. Major health inequalities among populations residing in Greek migrant camps were highlighted in this study. A change in the current migration policies of Greece and the European Union is urgently needed.


HPLC determination of estradiol, its degradation product, and preservatives in new topical formulation Estrogel HBF.
This paper deals with the development of a novel method for simultaneous determination of estradiol, its degradation product estrone, and two preservatives, methylparaben and propylparaben, in the topical preparation Estradiol HBF. After optimization of the analytical conditions the method was validated and applied in studies of the stability of the topical preparation Estrogel HBF. Separation of all these compounds was performed on a Supelco Discovery C18 (250 mm x 3.0 mm, 5 microm) analytical column. A mixture of acetonitrile, methanol, and water (23:24:53 v/ v) was chosen as mobile phase. UV absorbance at 225 nm was used for detection and quantitation of analytes. The total analysis time was less than 12 min at a flow rate of 0.9 mL min(-1). All the compounds were isolated from the topical gel by simple extraction with an acetonitrile solution of hydrocortisone, as internal standard, and using sonication and centrifugation thereafter. The supernatant was injected directly on to the analytical column. The recovery of the procedure was from 96.9 to 100.4%. Validation of method according international guidelines was successfully performed.


Effects of interleukin-15 (IL-15) on adipose tissue mass in rodent obesity models: evidence for direct IL-15 action on adipose tissue.
Interleukin-15 (IL-15) is a proinflammatory cytokine with multifunctional effects outside the immune system. Previous studies have indicated that treatment of normal rats with IL-15 reduces white adipose tissue (WAT) mass, but it was unclear if these effects were direct or indirect. In the present study, the effects of IL-15 on WAT mass and lipid metabolism were studied in two genetic models of obesity: the leptin receptor-negative fa/fa Zucker rat and the leptin-deficient ob/ob mouse. Lean Zucker rats, lean (+/+), and obese mice (ob/ob) responded to IL-15 with reductions in WAT mass and lipoprotein lipase activity (LPL), with no decreases in food intake. In contrast, fa/fa Zucker rats did not respond to IL-15 administration by any of the above measures of fat mass or lipid metabolism. In addition, ribonuclease protection assays (RPAs) were used to demonstrate that all three subunits (gamma(c), beta and alpha) of the IL-15 receptor complex are expressed by rat and mouse WAT, suggesting that the effects of IL-15 on adipose tissue metabolism could be direct. Additionally, the fa/fa rats expressed 84% lower levels of the gamma(c) signaling receptor subunit than lean Zucker rats, suggesting this decrease may play a role in the lack of adipose tissue response to IL-15 in the fa/fa genotype and lending further support for a direct action of IL-15 on adipose tissue.


The mental status evaluation. Application in the emergency department.
The mental status evaluation is a useful test in the emergency department. The major purposes of the examination are to determine the presence of neuropsychiatric illness and to determine whether this illness is functional or organic. The most accepted evaluation of mental status is the formal mental status evaluation. This extensive test is rarely necessary in the emergency department; rather a short test of cognitive function, such as the Cognitive Capacity Screening Examination or Mini-Mental Status Examination, may be more appropriate. With frequent repetition in use and the concomitant development of clear standards for interpretation of the examination used, the emergency physician will become more comfortable with bedside mental status testing.


Alterations of blood pulsations parameters in carotid basin due to body position change.
The velocity of the pulse wave (PWV) propagating through the vascular tree is an essential parameter for diagnostic the state of the cardiovascular system especially when it is measured in the pool of carotid arteries. In this research, we showed for the first time that the time of the blood-pressure-wave propagation from the heart to the face is a function of the body position. Significant asymmetry and asynchronicity of blood pulsations in the facial area were found in a recumbent position. Parameters of blood pulsations were measured by an advanced camera-based photoplethysmography system in 73 apparently healthy subjects. Most likely, observed changes of the blood-pulsation parameters are caused by variations of the arterial blood pressure due to hydrostatic pressure changes, and secondary reaction of blood vessels in response to these variations. Demonstrated feasibility of PWV measurements in the pool of carotid arteries provides considerable advantages over other technologies. Moreover, possibilities of the method to estimate physiological regulation of the peripheral blood flow (particularly, as a response to the gravitational changes) have been demonstrated. The proposed concept allows development of non-invasive medical equipment capable of solving a wide range of scientific and practical problems related to vascular physiology.


Relationship Between Changes in the Choroidal Structure and Blood Flow of the Macula After Trabeculectomy.
To elucidate the relationship between changes in the choroidal structure and blood flow of the macula after trabeculectomy. A prospective study of 30 eyes of 30 patients with glaucoma who underwent trabeculectomy. Enhanced depth imaging optical coherence tomography with choroidal image binarization and laser speckle flowgraphy of the macula were performed at baseline and 1, 3, and 6 months postoperatively. Mixed-effects models with adjustment for confounders were used to analyze longitudinal changes in the mean choroidal thickness (mCT), mean choroidal vascular thickness (mCVT), mean choroidal interstitial thickness (mCIT), and mean blur rate (MBR). The decrease in the intraocular pressure (IOP; 45%-51%) and axial length (0.5%-0.8%) and the increase in ocular perfusion pressure (OPP; 34%-38%), mCT (16%-19%), mCVT (16%-20%), mCIT (17%-20%), and MBR (22%-25%) were significant at each postoperative time point (all P < 0.001). In the multivariate analysis, the mCVT changes were positively correlated with the OPP and MBR changes (P = 0.04 and P < 0.001, respectively), whereas the mCIT changes were negatively correlated with IOP changes (P = 0.005). The MBR changes correlated significantly with changes in mCVT but not mCIT (P < 0.001 and P = 0.39, respectively). Thickness changes in the intraluminal and extraluminal parts of the choroid were closely associated with changes in blood flow and IOP, respectively, although both parts thickened comparably after IOP reduction by trabeculectomy. The choroid reacts to IOP reduction differently between the intraluminal and extraluminal areas, blood flow dependence in the vascular area, and IOP dependence in the stromal area.


Simvastatin attenuates the additive effects of TNF-α and IL-18 on the connexin 43 up-regulation and over-proliferation of cultured aortic smooth muscle cells.
Statin therapy is known to down-regulate inflammatory activities in atheromatous tissues of animals. The aims of this study were to examine the regulatory role of interleukin-18 (IL-18) in the connexin 43 (Cx43) and the proliferation of cultured aortic smooth muscle cells (SMCs) as well as to elucidate the underlying therapeutic mechanism of simvastatin. Vytorin therapy significantly alleviated high-cholesterol diet-induced hypercholesterolemia, suppressed neointimal hyperplasia, macrophage infiltration, and Cx43 and IL-18 expression in rabbit aortic walls. In vitro study using an aortic SMC line showed that IL-18 up-regulated constitutive Cx43 expression and potentiated tumor necrosis factor-α (TNF-α)-triggered Akt and MAPK signaling pathways. Simvastatin treatment alone reduced constitutive Cx43 levels and prevented the TNF-α-induced IL-18 up-regulation. Mechanistic investigation using kinase-specific inhibitors showed that simvastatin pretreatment attenuated TNF-α-elicited Akt and ERK1/2 phosphorylation, whereas PI3K and all MAPK activities were also implied in the additive effect of TNF-α and IL-18 on Cx43 up-regulation. Proliferation assay indicated that IL-18 stimulated SMC proliferation and synergized the TNF-α-stimulated cell proliferation. Likewise, simvastatin treatment suppressed the SMC over-proliferation induced not only by TNF-α alone, but also by simultaneous treatment with TNF-α and IL-18. The suppression of simvastatin in SMC proliferation was not mediated through mitochondrial related pro-apoptogenesis under both scenarios. In conclusion, simvastatin attenuates the additive effects of TNF-α and IL-18 on Cx43 up-regulation and over-proliferation of aortic SMCs, mainly through the blockade of Akt signaling pathway. These findings may fortify the rationale underlying the atheroprotective mechanism of statin therapy.


A CYP21A2 based whole-cell system in Escherichia coli for the biotechnological production of premedrol.
Synthetic glucocorticoids like methylprednisolone (medrol) are of high pharmaceutical interest and represent powerful drugs due to their anti-inflammatory and immunosuppressive effects. Since the chemical hydroxylation of carbon atom 21, a crucial step in the synthesis of the medrol precursor premedrol, exhibits a low overall yield because of a poor stereo- and regioselectivity, there is high interest in a more sustainable and efficient biocatalytic process. One promising candidate is the mammalian cytochrome P450 CYP21A2 which is involved in steroid hormone biosynthesis and performs a selective oxyfunctionalization of C21 to provide the precursors of aldosterone, the main mineralocorticoid, and cortisol, the most important glucocorticoid. In this work, we demonstrate the high potential of CYP21A2 for a biotechnological production of premedrol, an important precursor of medrol. We successfully developed a CYP21A2-based whole-cell system in Escherichia coli by coexpressing the cDNAs of bovine CYP21A2 and its redox partner, the NADPH-dependent cytochrome P450 reductase (CPR), via a bicistronic vector. The synthetic substrate medrane was selectively 21-hydroxylated to premedrol with a max. yield of 90 mg L(-1) d(-1). To further improve the biocatalytic activity of the system by a more effective electron supply, we exchanged the CPR with constructs containing five alternative redox systems. A comparison of the constructs revealed that the redox system with the highest endpoint yield converted 70 % of the substrate within the first 2 h showing a doubled initial reaction rate compared with the other constructs. Using the best system we could increase the overall yield of premedrol to a maximum of 320 mg L(-1) d(-1) in shaking flasks. Optimization of the biotransformation in a bioreactor could further improve the premedrol gain to a maximum of 0.65 g L(-1) d(-1). We successfully established a CYP21-based whole-cell system for the biotechnological production of premedrol, a pharmaceutically relevant glucocorticoid, in E. coli and could improve the system by optimizing the redox system concerning reaction velocity and endpoint yield. This is the first step for a sustainable replacement of a complicated chemical low-yield hydroxylation by a biocatalytic cytochrome P450-based whole-cell system.


Blood transfusion: a possible risk factor in retrolental fibroplasia.
The effect of blood transfusion on the occurrence of RLF was evaluated in 58 infants who weighed less than 1001 g at birth (Group I) and 70 oxygen treated infants of various birth weights (Group II). Although there was no significant difference between Group I infants with or without exchange transfusion as to birth weight, gestational age, duration of oxygen therapy, peak Pa02's, or multiple births, there was a significantly increased incidence of pre-retrolental fibroplasia in transfused over non-transfused Group II infants. When Group II infants were stratified for prematurity and oxygen duration, this difference persisted in those not already at risk for RLF. This increased incidence of retinopathy in transfused infants suggests that blood transfusion may be a risk factor in the pathogenesis of RLF.


Sperm sexing technology-the transition to commercial application. An introduction to the symposium "update on sexing mammalian sperm".
Over the past decade, procedures for sexing mammalian sperm by flow cytometry/cell sorting have been refined sufficiently for large-scale commercial application in cattle; millions of doses of sexed sperm are sold each year for artificial insemination. Furthermore, more than a hundred babies are born annually from use of sexed human sperm via artificial insemination or in vitro fertilization, and to a lesser extent by injection of single sperm into oocytes. Semen sexing technology is also being applied for various objectives in a number of other species. Accuracy of sexing is around 90% in most species. However, this technology is still rather expensive, and fertility of sexed sperm is lower than unsexed controls in most instances. Speakers in this symposium, "Update on sexing mammalian sperm," held in San Diego, California on 3 January 2009, presented the latest research on sexing sperm, including documentation of success rates. The written versions were peer-reviewed and follow in this issue of Theriogenology.


Nucleation and dissociation of methane clathrate embryo at the gas-water interface.
Among natural energy resources, methane clathrate has attracted tremendous attention because of its strong relevance to current energy and environment issues. Yet little is known about how the clathrate starts to nucleate and disintegrate at the molecular level, because such microscopic processes are difficult to probe experimentally. Using surface-specific sum-frequency vibrational spectroscopy, we have studied in situ the nucleation and disintegration of methane clathrate embryos at the methane-gas-water interface under high pressure and different temperatures. Before appearance of macroscopic methane clathrate, the interfacial structure undergoes 3 stages as temperature varies, namely, dissolution of methane molecules into water interface, formation of cage-like methane-water complexes, and appearance of microscopic methane clathrate, while the bulk water structure remains unchanged. We find spectral features associated with methane-water complexes emerging in the induction time. The complexes are present over a wide temperature window and act as nuclei for clathrate growth. Their existence in the melt of clathrates explains why melted clathrates can be more readily recrystallized at higher temperature, the so-called "memory effect." Our findings here on the nucleation mechanism of clathrates could provide guidance for rational control of formation and disintegration of clathrates.


Expression of cell cycle regulatory proteins (p53, pRb) in the human female genital tract.
Recent studies have shown that proliferation and differentiation of various cell types is regulated by cell-cycle-related proteins, such as protein p53 and retinoblastoma protein pRb. Three monoclonal antibodies to p53 (PAb240, PAb421, and PAb1801) and 3H9 monoclonal antibody to pRb were utilized for localization of proteins by peroxidase immunohistochemistry in frozen tissue sections. Nuclear and nucleolar p53 expression was detected in nondividing and relatively stable cells, e.g., oocytes in primordial follicles and granulosa lutein cells. On the other hand, strong cytoplasmic p53 expression was detected in proliferating and low differentiated epithelial cells of the ovarian surface epithelium, amnion, endocervix and ectocervix, indicating enhanced p53 synthesis. Not all three p53 antibodies reacted with each tissue, perhaps due to structural and conformational changes in the p53 molecule, accompanying p53 association with other proteins, e.g., tissue specific transcription factor interactions. pRb expression was usually restricted to the cell nuclei and nucleoli. However, glandular cells of the female reproductive tract showed cytoplasmic pRb expression in juxtaluminal (secretory) segments of cells, a feature not previously described in any cell type. p53 and pRb immunoreactivities declined with advanced differentiation of cells. No p53 or pRb was detected in placental syncytiotrophoblast or terminally differentiated squamous epithelial cells. Our data indicate that large quantities of p53 are synthesized in cells leaving the cell cycle and entering differentiation. Except in glandular cells, the pRb expression is confined to the cell nuclei and nucleoli. A unique cytoplasmic expression of pRb in juxtaluminal segments of glandular cells suggests a role for pRb in human female fertility and conception.


Identifying Cryptic Relationships.
Cryptic relationships such as first-degree relatives often appear in studies that collect population samples, including genome-wide association studies (GWAS) and next-generation sequencing (NGS) analyses. Cryptic relatedness not only increases type 1 error rate of association tests but also affects other analytical aspects of GWAS and NGS such as population stratification via principal component analysis. Here, we discuss three effective methods, as implemented in PREST, PLINK, and KING, to detect and correct for the problem of cryptic relatedness using high-throughput SNP data collected from GWAS and NGS experiments. We provide the analytical and practical details involved using three application examples.


Gastric access temporary for endoscopy (GATE): a proposed algorithm for EUS-directed transgastric ERCP in gastric bypass patients.
Performing endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y gastric bypass (RYGB) anatomy is technically challenging. Device-assisted enteroscopy and laparoscopic-assisted methods suffer from high failure rates and/or post-procedural complications. A novel endoscopic technique termed EUS-Directed Transgastric ERCP (EDGE) or Gastric Access Temporary for Endoscopy (GATE) has recently emerged, demonstrating excellent technical and therapeutic success. The technique involves endoscopic ultrasound-guided deployment of a lumen-apposing metal stent (LAMS) to gain access into the remnant stomach to facilitate standard ERCP. In this case series, we describe our center's experience and unique approach with the GATE procedure and discuss several key strategies and differences. Patients underwent the GATE procedure via a novel algorithmic approach. Key information on procedural details, technical and clinical success, follow-up, and adverse events was prospectively collected and retrospectively reviewed. 10 patients underwent the GATE procedure from May 2017 to March 2018. Technical and clinical success were both 100%. Gastric and jejunal access points for LAMS deployment were 30% and 70%, respectively. Total procedure time per patient, including LAMS deployment, ERCP, and all follow-up procedures, averaged 2.37 ± 0.63 h. 2 out of 10 patients (20%) had adverse events that were resolved either intra-procedurally or after repeat endoscopy with no long-term complications and none requiring surgery. For patients with complete follow-up (n = 7), access tract closure rate was 100% with the aid of a temporary plastic double pigtail stent to facilitate closure. GATE appears to be a safe and effective procedure and may be considered the preferred approach to ERCP in patients with RYGB anatomy at centers with LAMS experience. The procedure offers more definitive and higher range of ERCP interventions compared to traditional methods and is associated with fewer adverse events. Improvements in strategies and methods with the GATE technique may reduce risks and improve outcomes.


Antibiotic use and good practice in 314 French hospitals: The 2010 SPA2 prevalence study.
We aimed to assess antibiotic prescriptions to identify potential targets for improvement. We conducted a point prevalence survey (November 2010) of antibiotic use in 314 voluntary hospitals recruited by the French Infectious Diseases Society (SPILF) and the National Observatory for Epidemiology of Bacterial Resistance to Antimicrobials (ONERBA). Data were entered online, immediately analyzed and exported. The prevalence of antibiotic use was 19.5% (9059/46,446patients). A higher prevalence was observed in the infectious disease (58.4%), hematology (58%), and intensive care (48.7%) units. The three most frequently used antibiotic classes were aminopenicillins (23.8%), fluoroquinolones (17.9%), and 3rd-generation cephalosporins (16.7%). A monotherapy was prescribed to 64% of patients. The reasons for the antibiotic prescription were written in the medical records of 74% of patients and 62% were consistent with the local guidelines. Our results are similar to that of other studies. Various local targets for improvement have been identified to help hospitals define a better antibiotic stewardship.


Down-regulation of stathmin is required for TGF-beta inducible early gene 1 induced growth inhibition of pancreatic cancer cells.
Transforming growth factor-beta (TGF-beta) inducible early gene 1 (TIEG1) is known to induce apoptosis in TGF-beta sensitive pancreatic cancer cells, yet its effect on TGF-beta resistant cancer cells remains unclear. In this study, TIEG1 was found to induce apoptosis in TGF-beta resistant cancer cells and concurrently enhanced gemcitabine chemosensitivity. Down-regulation of stathmin was noted to associate with TIEG1 expression, whilst ectopic overexpression of stathmin prevented TIEG1 mediated growth inhibition of tumor cells. Small interfering RNAs targeting stathmin inhibited pancreatic cancer cell growth. These suggest that stathmin is a downstream target of TIEG1.


Prediction and evaluation of groundwater level changes in an over-exploited area of the Baiyangdian Lake Basin, China under the combined influence of climate change and ecological water recharge.
Groundwater (GW) and surface water (SW) are important components of water resources and play key roles in social and economic development and regional ecological security. There are currently several stresses placing immense pressure on the GW resources of the Baiyangdian Lake Basin (BLB) in China, including climate change. A series of ecological and environmental challenges have manifested in the plain area of the BLB due to long-term over-exploitation of GW, including regional declines in GW level, aquifer drainage, land subsidence, and soil secondary salinization. Climate change may aggravate environmental challenges by altering GW recharge rates and availability of GW. This study applied the fully processed and physically-based numerical models, MODFLOW and the Soil & Water Assessment Tool (SWAT) in a semi-coupled modeling framework. The aim of the study was to quantitatively analyze changes to shallow GW levels and reserves in the plain area of BLB over the next 15 years (2021-2035) under climate change and different artificial recharge schemes. The results indicated that GW storage and levels are rising under the different GW recharge schemes. The maximum variation in the GW level was 20-30 m under a rainfall assurance rate of 50% and water level in the depression cone increased 14.20-14.98 m. This study can act as a theoretical basis for the development of a more sustainable GW management scheme in the plain area of the BLB and for the management and protection of aquifers in other areas with serious GW overdraft.


Does Timing of Robotic Esophagectomy Adoption Impact Short-Term Postoperative Outcomes?
Robotic esophagectomies are increasingly common and are reported to have superior outcomes compared with an open approach; however, it is unclear if all institutions can achieve such outcomes. We hypothesize that early adopters of robotic technique would have improved short-term outcomes. The National Cancer Database (2010-2016) was used to identify robotic esophagectomies. Early adopters were defined as programs which performed robotic esophagectomies in 2010-2011, late adopters in 2012-2013. Outcomes of esophagectomies performed between 2014 and 2016 were compared and included length of stay, number of lymph nodes evaluated, readmission, conversion rate, and 90-day mortality. Multivariable regressions, accounting for robotic esophagectomy volume, were used to control for confounding factors. There were 37 early adopters and 35 late adopters. Between 2014 and 2016, 683 robotic esophagectomies were performed: 446 (65.3%) by early adopters and 237 (34.7%) by late adopters. Early adopters were more likely to be academic programs (96.2 versus 72.8%, P < 0.01). Other clinical and demographic variables were similar. Late adopters were found to have decreased a number of lymph nodes evaluated (coefficient -2.407, P = 0.004) compared with early adopters. There were no significant differences in length of stay, readmissions, rate of positive margins, conversion from robotic to open, or 90-day mortality. When accounting for robotic esophagectomy volume, late adoption of robotic esophagectomy was associated with a reduced lymph node harvest, but other postoperative outcomes were similar. These data suggest that programs can safely start new robotic esophagectomy programs, but must ensure an adequate case load.


Immune microenvironment features and efficacy of PD-1/PD-L1 blockade in non-small cell lung cancer patients with EGFR or HER2 exon 20 insertions.
Insertions in exon 20 (Ex20ins) of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are relatively insensitive to first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). This study aimed to investigate the immune microenvironment features and efficacy of PD-1/PD-L1 blockade of NSCLC with EGFR and HER2 Ex20ins. Clinical characteristics, coexisting mutations, and outcomes to EGFR-TKIs and immune checkpoint blockade were reviewed for NSCLC patients with exon 20 mutations of EGFR or HER2. Data obtained included the molecular spectrum (extended genotyping for mutations in 324 cancer-related genes), as well as tumor mutational burden (TMB), PD-L1 protein expression, and the abundance of CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs). A total of 1270 NSCLC patients were identified. Of these, 504 (39.7%) cases had EGFR mutations and 6.9% (35/504) of them had EGFR Ex20ins. Meanwhile, 21 (1.7%) cases with HER2 Ex20ins were detected. Comprehensive genomic profiling identified A767_V769dup variant (25.0%) was the most common type in tumors with EGFR Ex20ins. Co-occurring mutations were not uncommon including TP53 (45%), PIK3CA (20%), CDKN2A (10%), and EGFR amplification (20%). The average TMB was 3.3 mutations/megabase. PD-L1 expression in patients with EGFR Ex20ins was significantly higher than for those with HER2 mutations (48.6% vs. 19.0%, P = 0.027). High TMB and PD-L1 expression was independently associated with significantly poor prognosis (P = 0.025, P = 0.045, respectively) while there was no association between CD4+/CD8+ TILs and prognosis in EGFR or HER2 mutant NSCLC. Finally, patients harboring EGFR Ex20ins seemed to be sensitive to PD-1/PD-L1 blockage whereas it showed limited efficacy in patients with HER2 Ex20ins. NSCLC patients with EGFR/HER2 Ex20ins had similar genomic characteristics and distinct immune features. Patients with EGFR Ex20ins had significantly higher PD-L1 expression than those with HER2 mutations, which may be the potential reason for the different responses to PD-1/PD-L1 blockage.


Herpesvirus quiescence in neuronal cells. V: forskolin-responsiveness of the herpes simplex virus type 1 alpha0 promoter and contribution of the putative cAMP response element.
The herpes simplex virus (HSV)-1 alpha0 promoter contains a putative cAMP response element (CRE) located at positions -68 to -60 with respect to the initiation of transcription. In this report, the authors examined the functionality of this element using (1) luciferase reporter gene assays in nerve growth factor-differentiated (ND)-PC12 cells and (2) virus-induced activation from quiescently infected (QIF)-PC12 cells. The putative alpha0 CRE was completely eliminated by digestion with the restriction enzyme Tsp45I followed by mung bean nuclease treatment. The mutated region was verified by DNA sequencing and was inserted into the alpha0-luciferase reporter plasmid (pRDalpha0-LUC) creating (pRDalpha0deltaCRE-LUC), and into the HSV-1 genome of strain 17(+)(alpha0deltaCRE). Insertion into both copies of the alpha0 promoter was verified by Southern blot analysis. ND-PC12 cells transfected with pRDalpha0-LUC and pRDalpha0deltaCRE-LUC plasmids responded similarly to forskolin (50 microM), with approximately 250% increases in luciferase activity compared to mock-treated cultures as measured 3 days following treatment. When QIF-PC12 cultures established with HSV-1 strain 17(+) and alpha0deltaCRE were treated with forskolin (50 microM) 17 days post infection, virus was detected in 9/24 (37.5%) and 13/24 (54.2%) of induced cultures by day 8 post treatment, respectively. In contrast, virus was detected in 0/23 and 1/24 (4.2%) of mock-treated cultures by day 8 post treatment for wild-type and mutant viruses, respectively. These findings indicate that the alpha0 promoter is forskolin responsive, the purported CRE of the alpha0 promoter does not confer forskolin responsiveness in ND-PC12 cells, and this element is not required for reactivation of HSV-1 from QIF-PC12 cells.


Endothelial injury by nicotine and its prevention.
Nicotine administered i.v. or p.o. in doses above 0.0125 mg/kg to the rat caused a highly significant increase in circulating anuclear carcasses of endothelial cells estimated by an original method. This effect of nicotine was completely prevented by a prior oral administration of the flavonoids hydroxyethylrutosides (HR) or Mono-7-HR.


Testing the resistance of single- and multi-walled carbon nanotubes to chemothermal oxidation used to isolate soots from environmental samples.
Quantification of natural and engineered carbon nanotubes (CNT) in the environment is urgently needed to study their occurrence and fate and to enable a proper risk assessment. Currently, such methods are lacking. Here, we tested the resistance of 15 structurally different CNTs to chemothermal oxidation at 375 degrees C (CTO-375), a method used to isolate soots from environmental samples. Depending on their structure, CNTs survived CTO-375 in proportions ranging from 26 to 93%. Standard addition of CNTs to soil and sediment yielded recoveries between 66 and 171%, demonstrating the capability of CTO-375 to isolate CNTs from complex environmental matrices. These data of pure and added CNTs correspond to recoveries obtained with "ordinary" soots under similar experimental conditions. Hence, soot fractions commonly isolated with CTO-375 from environmental matrices most probably encompass CNTs. Future work should attempt to enhance the method's selectivity, i.e., its capability to separate CNTs from other forms of soot.


Influence of interferon on the growth of primary ovarian carcinoma cells in a semi-solid agar system: comparison with clinical effects of interferon therapy.
The sensitivity of primary human ovarian cancer cells to interferon (IFN) was studied in vitro by the use of a tumor cloning system in semi-solid agar. Tumor colonies were found in 37% (34/93) of the experiments with tumor cells from ascites and in 35% (6/17) of the experiments with solid tumors. The relative colony-forming ability could not be correlated to prior treatment. In 15 out of 18 patients the ascitic tumor cells were sensitive to IFN-alpha. Sensitivity was found in one test out of three with solid tumors. The sensitivity was dependent on the dose of IFN but could vary for the natural IFNs alpha and gamma. In seven patients the relation between in vitro and in vivo sensitivity of the tumor cells to IFN could be studied. Any correlation between in vitro and in vivo sensitivity could not be revealed in this small group of patients.


The comparative evaluation of transcrestal and lateral sinus floor elevation in sites with residual bone height ≤6 mm: A two-year prospective randomized study.
To compare clinical and radiographic outcomes between transcrestal sinus floor elevation (TSFE) and lateral sinus floor elevation (LSFE) approaches of simultaneous implant placement in atrophic maxilla. Patients with a residual bone height (RBH) ≤6 mm were enrolled and randomly assigned to TSFE and LSFE groups. Patients in both groups simultaneously underwent sinus floor elevation with bovine-derived xenograft and implant placement. Clinical and radiographic results were evaluated immediately after surgery and after 6, 12, 18, and 24 months. The endo-sinus bone gain (ESBG), apical implant bone height (ABH), endo-sinus bone-implant contact rate (EBICR), and crestal bone level (CBL) were assessed using panoramic radiographs. Forty-one implants (TSFE: 21, LSFE: 20) were placed in cases with a mean RBH of 3.77 ± 1.16 mm. All implants obtained clinical success and satisfactory ESBG at 24 months. No significant differences were found in ESBG and ABH between two groups immediately after surgery, but LSFE group showed significantly higher values than TSFE group thereafter. Grafts in TSFE group reached stability 6 months earlier than that in LSFE group. In both groups, EBICR was almost 100%, and CBL showed no detectable changes. LSFE can achieve higher ESBG 2 years after surgery. Otherwise, TSFE could be an alternative to LSFE, when the access for lateral window preparation is limited. Both approaches were highly predictable for RBH ≤6 mm during 24-month observation period for the implants placed simultaneously.


Primary prevention in community mental health centers: a survey of current activity.
About half of the current activity in consultation and education services of community mental health centers can be classified as primary prevention. Using a framework that distinguishes between institutional-level interventions (caretaker training and program consultation) and individual-level interventions (dealing with developmental or situational crises) data are presented from 43 community mental health centers on (a) specific target populations that are tapped by primary-prevention activities and (b) content of the activities. Illustrative activities are described and explanations of current trends are posited. Current programming trends in primary prevention reflect the "state of the art" today and the findings in this paper have implications for the future promotion of primary prevention activity.


Cognitive, behavioral, and social factors are associated with bias in dietary questionnaire self-reports by schoolchildren aged 9 to 11 years.
Measuring children's dietary behavior is central to evaluating interventions and identifying predictors and outcomes of dietary behaviors. Systematic biases may obscure or inflate associations with self-reported intakes. To identify cognitive, behavioral, and social correlates of bias in children's reporting of breakfast items on a self-completion questionnaire. Cross-sectional survey. Children completed standardized tests of episodic memory, working memory, and attention, and a questionnaire assessing attitudes toward breakfast. Teachers completed a classroom behavior measure. Associations between measures and children's underreporting of breakfast foods (ie, cereals, bread, milk, fruits, sweet items, and potato chips) on a self-completion questionnaire relative to validated 24-hour recall were examined. Subjects were aged 9 to 11 years (n=678). Data were collected from 111 schools throughout Wales in 2005. A larger percentage of less-healthful breakfast items (ie, sweet snacks and potato chips) than more healthful items (ie, fruit, cereals, bread, and milk) were omitted from questionnaire self-reports. Children from lower socioeconomic status schools omitted more items than those from wealthier schools (Kruskal-Wallis H=12.51, P<0.01), with omissions twice as high for less-healthful items than for more-healthful items within the lowest socioeconomic status schools. Those with positive attitudes (H=23.85, P<0.001), better classroom behavior (H=6.26, P<0.05), and better episodic memory (H=8.42, P<0.05) omitted fewer items than those with negative attitudes, poorer behavior, and poorer episodic memory. Children who ate more items omitted more than those who ate fewer (H=47.65, P<0.001). No differences were observed in terms of attention and working memory. Episodic memory, classroom behavior, attitudes, socioeconomic status, and total items consumed are associated with bias in questionnaire self reports. Such biases have implications for examination of associations between breakfast eating and cognitive and behavioral factors, examination of effect modification by socioeconomic status in intervention trials, and for the sensitivity of measures to detect intervention effects.


Application of semi-preparative high-performance liquid chromatography to difficult natural product separations.
Semi-preparative high-performance liquid chromatography on RP-18 with methanol-water as the mobile phase was used for the separation of homologous antifungal chromenes and related homologous dichromenes from Hypericum revolutum Vahl (Guttiferae). In the course of the structural elucidation of new saponins from Phylolacca dodecandra L'Hérit. (Phytolaccaceae), two isomeric oleanane saponins were separated on RP-8 with acetonitrile-water as the mobile phase.


Lipophilicity predicts the ability of nonsulphonylurea drugs to block pancreatic beta-cell KATP channels and stimulate insulin secretion; statins as a test case.
KATP ion channels play a key role in glucose-stimulated insulin secretion. However, many drugs block KATP as "off targets" leading to hyperinsulinaemia and hypoglycaemia. As such drugs are often lipophilic, the aim was to examine the relationship between drug lipophilicity (P) and IC 50 for KATP block and explore if the IC 50's of statins could be predicted from their lipophilicity and whether this would allow one to forecast their acute action on insulin secretion. A meta-analysis of 26 lipophilic, nonsulphonylurea, blockers of KATP was performed. From this, the IC 50's for pravastatin and simvastatin were predicted and then tested experimentally by exploring their effects on KATP channel activity via patch-clamp measurement, calcium imaging and insulin secretion in murine beta cells and islets. Nonsulphonylurea drugs inhibited KATP channels with a Log IC 50 linearly related to their logP. Simvastatin blocked KATP with an IC 50 of 25 nmol/L, a value independent of cytosolic factors, and within the range predicted by its lipophilicity (21-690 nmol/L). 10 μmol/L pravastatin, predicted IC 50 0.2-12 mmol/L, was without effect on the KATP channel. At 10-fold therapeutic levels, 100 nmol/L simvastatin depolarized the beta-cell membrane potential and stimulated Ca2+ influx but did not affect insulin secretion; the latter could be explained by serum binding. The logP of a drug can aid prediction for its ability to block beta-cell KATP ion channels. However, although the IC 50 for the block of KATP by simvastatin was predicted, the difference between this and therapeutic levels, as well as serum sequestration, explains why hypoglycaemia is unlikely to be observed with acute use of this statin.


Development of sand-plastic composites as floor tiles using silica sand and recycled thermoplastics: a sustainable approach for cleaner production.
Strict environmental concerns, depleting natural recourses, and rising demand for building construction materials have promoted scientific research toward alternative building materials. This research supports the idea of sustainability and a circular economy via the utilization of waste to produce value-added products. The research explored the potential of waste plastics and silica sand for developing thermoplastic composite as floor tiles. The samples were characterized by water absorption, compressive strength, flexural strength, and sliding wear. The morphological analysis of the sand-plastic interfaces was covered under the umbrella of this study. The maximum compressive and flexural strength were found to be 46.20 N/mm2 and 6.24 N/mm2, respectively, with the minimum water absorption and sliding wear rate of 0.039% and 0.143 × 10-8 kg/m, respectively. The study suggests the workability of the developed floor tiles in non-traffic areas of public places. Thus, the study provides a green building material through recycling waste plastics for sustainable development.


Finding Nivo: A Case Report of 2 Forms of Nivolumab-Induced Liver Injury in an Allograft Liver in the Immediate Post-Transplant Period.
Recent reports have emerged regarding the utilization of checkpoint inhibitors for downstaging hepatocellular carcinoma before liver transplantation. Early post-transplant acute cellular rejection has rarely led to graft loss. We report the first case of 2 forms of nivolumab-associated liver injury on biopsy of the allograft organ in a single patient who received nivolumab for cancer downstaging before liver transplantation: 1. mild acute cellular rejection according to Risk Analysis Index scoring and 2. zone 3 inflammation and apoptosis consistent with a more classic drug-induced liver injury pattern. This case not only adds further evidence about the risk for rejection post-transplant, but sheds light on other injuries checkpoint inhibitors can cause to the allograft.