Risks versus benefits of gastrointestinal endoscopy during pregnancy.
Although gastrointestinal endoscopy is generally safe, its safety must be separately analyzed during pregnancy with regard to fetal safety. Fetal risks from endoscopic medications are minimized by avoiding FDA category D drugs, minimizing endoscopic medications, and anesthesiologist attendance at endoscopy. Esophagogastroduodenoscopy seems to be relatively safe for the fetus and may be performed when strongly indicated during pregnancy. Despite limited clinical data, endoscopic banding of esophageal varices and endoscopic hemostasis of nonvariceal upper gastrointestinal bleeding seems justifiable during pregnancy. Flexible sigmoidoscopy during pregnancy also appears to be relatively safe for the fetus and may be performed when strongly indicated. Colonoscopy may be considered in pregnant patients during the second trimester if there is a strong indication. Data on colonoscopy during the other trimesters are limited. Therapeutic endoscopic retrograde cholangiopancreatography seems to be relatively safe during pregnancy and should be performed for strong indications (for example, complicated choledocholithiasis). Endoscopic safety precautions during pregnancy include the performance of endoscopy in hospital by an expert endoscopist and only when strongly indicated, deferral of endoscopy to the second trimester whenever possible, and obstetric consultation.


Clinical parameter of odontoma with special emphasis on treatment of impacted teeth-a retrospective multicentre study and literature review.
Odontoma-separated into complex (CxOD) and compound (CpOD) subtypes-represents the most frequent odontogenic malformation. Retention of permanent teeth is a common symptom. Therefore, in a series of odontomas, an analysis of the management of retained teeth was conducted. In a retrospective multicenter study of two University Medical Centers and one private praxis in Germany, demographic and clinical data regarding odontomas from 01/2000-03/2015 were obtained. In particular, the influence of operative therapy on the dentition and on the treatment of impacted teeth was analyzed. Forty-five patients with 15 CxOD and 30 CpOD were included. Initial symptoms were delayed eruption of permanent teeth (n = 11), pain (n = 4), and swellings (n = 2); 28 cases were discovered by incidence, all of them via panoramic radiographs. The mandible/maxilla ratio was about 1:0.55 (29/16). Thirty-five out of 45 odontomas were in close proximity of at least one tooth (n = 16 at molars). A total of 14 teeth were extracted (CxOD: n = 5; CpOD: n = 9). Extractions had to be conducted more often in older patients (mean age 39.8 vs. 25.6 years). Of the non-extracted teeth, 8 teeth were displaced and retained. Of those, 4 teeth were aligned in the dental arch via orthodontic help and 2 teeth erupted spontaneously after operation during the follow-up period. In all cases, no relapse was seen. Odontomas can cause displacement as well as malformation and resorption of the adjacent teeth. Mostly, removal of odontomas is conducted. Extirpation of odontoma can allow for normal tooth eruption, often rendering extractions avoidable. Orthodontic alignment, though sometimes challenging, is a reasonable therapeutic option. These findings underline the value of the panoramic radiograph in preventive dentistry in younger patients.


Rate-dependent change in dispersion of repolarisation during ventricular pacing in man.
The difference between the end of monophasic action potentials recorded in the outflow tract of right ventricle and the T-wave on the surface electrocardiogram was measured as an estimate for disparity of termination of repolarisation. It was measured during right ventricular pacing at three basic cycle lengths 500, 600 and 700 msec and programmed stimulation with single extra stimuli in 15 patients with coronary arterial disease. The disparity of termination of repolarisation was rate dependent, showing increased values when stimulated at cycle length of 700 ms compared to 600 msec (P less than 0.005) and 500 ms (P less than 0.001). Premature stimulation revealed three different modes in changes of dispersion: in six patients the premature dispersion was increased at the shortest coupling intervals from the effective refractory period. It was unchanged compared to basic values in four, and in the rest of the patients the premature dispersion was reduced at the shortest coupling intervals. These results show that the dispersion of recovery of repolarisation increases at the lower stimulation frequencies. Premature dispersion is not always increased in the closest proximity to V-ERP during programmed ventricular stimulation in patients with ischemic heart disease.


Differential susceptibilities of Anopheles albimanus and Anopheles pseudopunctipennis to infections with coindigenous Plasmodium vivax variants VK210 and VK247 in southern Mexico.
The susceptibilities to coindigenous Plasmodium vivax of colonized Anopheles albimanus and Anopheles pseudopunctipennis from southern Mexico were investigated by simultaneous feeding with infected blood obtained from patients. The genes encoding circumsporozoite protein variant types (VK210 and VK247) in blood samples were determined by PCR and oligonucleotide probe hybridization. A. albimanus was more susceptible to VK210, and A. pseudopunctipennis was more susceptible to VK247.


Molecular interaction of sulfonamides and ovalbumin, an allergenic egg protein, exploring biophysical, theoretical and biological studies.
Biophysical, theoretical and biological in vitro studies were carried out to evaluate the interaction of the main allergen protein of egg white (ovalbumin, OVA) with sulphonamides (SA): sulphathiazole (S1), sulfaquinoxaline (S2), sulfadimethoxine (S3) and sulfamethazine (S4). The binding constants for the OVA-SA supramolecular complexes ranged from 1.20 to 30.66 × 105 M-1, observing the following order of affinity: S1 > S2 > S4 > S3. The preferential forces in the stabilization of the OVA complexes with S2 and S3 were hydrogen bonds and Van der Waals forces, whereas for OVA-S1 and OVAS4, were electrostatic interactions. Interaction process led to a change in the native structure of the protein, which may potentiate its natural allergenicity. Cations Ca(II), Mg(II) and Fe(III) favor the interaction of OVA with S1 and S2. The theoretical studies performed were consistent with the spectroscopic data. Finally, it was found that the interaction process for sulfonamides evaluated with OVA change the inhibition activity profile these antibiotics against strains of Escherichia coli ATCC 25922 and Bacillus megaterium APFSG3isox, but not the minimal inhibitory concentration values.


Development of rapid and effective oil-spill response system integrated with oil collection, recovery and storage devices for small oil spills at initial stage: From lab-scale study to field-scale test.
In the present study, through the laboratory-to-field scale experiments and trials, we report the development and evaluation of an integrated oil-spill response system capable of oil collection, recovery (separation), and storage, for a timely and effective response to the initial stage of oil-spill accidents. With the laboratory-scale experiments, first, we evaluate that the water-surface waves tend to abate the oil recovery rate below 80% (it is above 95% for the optimized configuration without the waves), which is overcome by installing the hydrophilic (and oleophobic) porous structures at the inlet and/or near the water outlet of the separator. In the follow-up meso-scale towing tank tests with a scaled-up prototype, (i) we optimize the maneuverability of the assembled system depending on the speed and existence of waves, and (ii) evaluate the oil recovery performance (more than 80% recovery for the olive oil and Bunker A fuel oil). Although more thorough investigations and improvements are needed, a recovery rate of over 50% can be achieved for the newly enforced marine fuel oil (low sulfur fuel oil, LSFO) that was not targeted at the time of development. Finally, we perform a series of field tests with a full-scale system, to evaluate the rapid deployment and operational stability in the real marine environment. The overall floating balance and coordination of each functional part are sustained to be stable during the straight and rotary maneuvers up to the speed of 5 knots. Also, the collection of the floating debris (mimicking the spilled oil) is demonstrated in the field test. The present system is now being tested by the Korea Coast Guard and we believe that it will be very powerful to prevent the environmental damage due to the oil spills.


Effects of prolonged exposure to low pH on enzymatic and non-enzymatic antioxidants in Japanese Medaka (Oryzias latipes).
Acidification in aquatic ecosystems is a major concern worldwide. In freshwater, although there are several publications reporting acute toxicity and adverse effects due to low pH, little is known about adverse effects on antioxidant mechanisms in fish after prolonged exposure. This study aimed to investigate how antioxidants are affected by raising larval Japanese Medaka (Oryzias latipes) in soft water at pH5.5, 6.0, and 6.5. After 18days of exposure, glutathione concentration and glutathione peroxidase activity in whole body homogenates increased as pH decreased, without changes in lipid peroxidation measured as thiobarbituric acid reactive substances. This study showed that prolonged exposure to low pH increased reactive oxygen species production and that fish cope with it by increasing levels of enzymatic and non-enzymatic antioxidants.


Association between spirometry pattern, left ventricular diastolic function, and mortality.
Spirometric abnormalities have been related to incident heart failure in general population, who generally have preserved left ventricular ejection fraction (LVEF). We aimed to investigate the association between spirometric indices, cardiac functions and clinical outcomes. Subjects presenting with exertional dyspnoea and received spirometry and echocardiography were eligible for this study. Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1)/FVC ratio were measured to define the spirometry patterns: normal (FEV1/FVC ≥ 70%, FVC ≥ 80%), obstructive (FEV1/FVC < 70%, FVC ≥ 80%), restrictive pattern (FEV1/FVC ≥ 70%, FVC < 80%) and mixed (FEV1/FVC < 70%, FVC < 80%). The diastolic dysfunction index (DDi) was the counts of the indicators, including septal e' velocity <7 cm/s, septal E/e' > 15, pulmonary artery systolic pressure > 35 mmHg and left atrial dimension >40 mm. Among a total of 8669 participants (65.8 ± 16.3 years, 56% men), 3739 (43.1%), 829 (9.6%), 3050 (35.2%) and 1051 (12.1%) had normal, obstructive, restrictive and mixed spirometry pattern, respectively. Subjects with restrictive or mixed spirometry pattern had higher DDi and worse long-term survival than those with obstructive or normal ventilation. FVC but not FEV1/FVC was predictive of 5-year mortality, independent of age, sex, renal function, LVEF, DDi, body mass index, and comorbidities (hazard ratio, 95% confidence intervals: .981, .977-.985). Furthermore, there was an inverse nonlinear relationship between FVC and DDi, suggesting the declined FVC may mediate 43% of the prognostic hazard of left ventricular diastolic dysfunction. The restrictive spirometry pattern or the declined FVC was associated with left ventricular diastolic dysfunction, which aggravated the long-term mortality in the ambulatory dyspnoeic subjects.


Best of both worlds: A career in technology transfer and business development.
The current academic and business landscape does not provide a clear path for doctoral trainees graduating. Moreover, the fundamental need of the hour is diversification of the workforce where PhD graduates need to be trained to do more beyond basic scientific research. One of the possible paths that is now becoming popular as science enters its translational phase is research commercialization and technology transfer. This short article provides an comprehensive overview of the technology transfer field and possible paths trainees can take to position themselves as a successful technology transfer professional.


Laparoscopic removal of a dermoid cyst in one ovary and an endometrioma in the other: A case report and literature review.
The coexistence of an endometrioma and a dermoid cyst is very uncommon, and there are few case reports of both conditions in the ovaries. A 41-year-old patient presented with left pelvic pain. She was referred with a bilateral pelvic mass. Magnetic resonance imaging (MRI) confirmed a dermoid cyst on the left ovary and an endometrioma on the right side. The patient was taking ibuprofen to relieve pain until the day of surgery. She was advised to proceed with bilateral laparoscopic cystectomy. During the laparoscopic procedure, the inspection showed that ovaries were bilaterally enlarged with cystic appearances. Bilateral ovarian cystectomy was performed in which a left dermoid cyst was removed intact within the ovary followed by a rupture of the endometrioma on the right. The patient tolerated the procedure without any complications. This case of coexistence of endometrioma and dermoid cyst in each ovary, confirmed by MRI due to atypical findings on ultrasound, highlights how efficient removal of both cyst is crucial.


Quantifying DNA-protein interactions by single molecule stretching.
In this chapter, we discuss a new method for quantifying DNA-protein interactions. A single double-stranded DNA (dsDNA) molecule is stretched beyond its contour length, causing the base pairs to break while increasing the length from that of dsDNA to that of ssDNA. When applied in a solution containing DNA binding ligands, this method of force-induced DNA melting can be used to quantify the free energy of ligand binding, including the free energy of protein binding. The dependence of melting force on protein concentration is used to obtain the equilibrium binding constant of the ligand to DNA. We have applied this method to a well-studied DNA-binding protein, bacteriophage T4 gene 32 protein (gp32), and have obtained binding constants for the protein to single-stranded DNA (ssDNA) under a wide range of solution conditions. Our analysis of measurements conducted at several salt concentrations near physiological conditions indicates that a salt-dependent conformational change regulates DNA binding by gp32.


Modulation of acetylcholine release via GABAA and GABAB receptors in rat striatum.
In order to investigate whether changes in acetylcholine (ACh) release induced by GABA receptors are due to a direct or indirect effect on cholinergic neurons in the striatum, GABAA and GABAB receptor bindings were assayed in the striatum microinjected with ethylcholine mustard aziridinium ion (AF64A), a cholinergic neurotoxin. Intra-striatal injection of a selective concentration of AF64A (10 nmol) reduced GABAA receptor binding without significantly altering GABAB receptor binding. Treatment with a higher, less selective concentration of AF64A (20 nmol) reduced all markers examined. These results suggest that GABAA, but not GABAB receptors, are located on cholinergic neurons in the striatum, and that GABA can directly modulate ACh release through stimulation of GABAA receptors. Findings further suggest that GABA can also indirectly modulate ACh release through stimulation of GABAB receptors located on non-cholinergic neuronal elements in the striatum.


Determination of seventeen endocrine disruptor compounds and their spatial and seasonal distribution in Ria Formosa Lagoon (Portugal).
In spite of its outstanding ecological and touristic importance the Ria Formosa Lagoon shows signs of anthropogenic pollution. Nonetheless, until the present survey no studies had ever documented the measurement of natural and pharmaceutical estrogens (17β-estradiol, estrone, and 17α-ethynylestradiol), xenoestrogenic industrial pollutants (4-octylphenol, 4-nonylphenol, and their mono and diethoxylates and bisphenol A), phytoestrogens (formononetin, biochanin A, daidzein, genistein), and sitosterol in this area. The 17 compounds measured herein are known as endocrine disrupters (EDCs) and act over the endocrine system even in few amounts (ng L(-1)-μg L(-1)). Thus to conclude about the influx of EDCs in the lagoon, water samples were taken every 2 months, during 1 year (2010), in low tide at nine sites distributed along the coastline. Water samples (1 L) were preconcentrated in the Oasis HLB cartridges and cleaned in silica cartridges before their analysis by GC-MS. Data showed the ubiquitous presence of potentially hazardous amounts of estrogens (particularly of ethynylestradiol, up to 24.3 ng L(-1)), nonylphenol (up to 547 ng L(-1)), and sitosterol (up to 12,300 ng L(-1)), mainly in summer, suggesting that the increase of the local number of inhabitants (tourists), the rise of the water temperature (up to 26 °C), and the blooming of local flora may interfere with the water quality parameters. This makes the lagoon a potential model to study. Taking into account the data, it was concluded that there are conditions for the occurrence of endocrine disruption in aquatic animals, even in areas included in the natural park of the Formosa. Besides, both the high amounts of un-ionized ammonia (up to 0.3 mg L(-1)) and phosphates (up to 1.6 mg L(-1)) my pose risks for local fauna and humans.


Endothelium-dependent relaxation in human saphenous vein grafts. Effects of preparation and clinicopathologic correlations.
Activity of endothelium-dependent relaxation factor (EDRF) was measured in 139 open ring preparations of fresh human saphenous vein from 85 patients undergoing coronary bypass grafting. The veins were constricted with phenylephrine and relaxed with the EDRF-dependent agents calcium ionophore A23187 or acetylcholine. EDRF activity produced a 36% +/- 4% relaxation of baseline contraction in response to calcium A23187. Vein graft preparation with room-temperature heparinized normal saline and pressurization to 400 mm Hg caused EDRF relaxation to fall to 10.6% +/- 2.0% versus 32.4% +/- 3.4% for control segments (p less than 0.05). Storage alone in room-temperature saline reduced EDRF response to 17.4% +/- 3.9% versus a control of 29.6% +/- 4.7% (p less than 0.05). Storage in heparinized room-temperature blood produced relaxation of 31.4% +/- 4.3% versus 34.1% +/- 5.7% (p less than 0.05). Storage in Plasma-Lyte solution (Travenol Laboratories, Inc., Deerfield, Ill), produced relaxation of 28.4% +/- 6.3% versus 30.1% +/- 5.3% (control) (p greater than 0.05). Veins stored at 2 degrees to 4 degrees C had severe depression of EDRF: 18.2% +/- 4.0% versus 34.0% +/- 5.4% for 37 degrees C storage (p less than 0.05). Pressurization to 400 mm Hg lessened EDRF relaxation: 20% +/- 3% versus 34% +/- 4% (control) (p less than 0.05), and use of nitroglycerin, papaverine, or verapamil produced no improvement. Twenty-eight vein grafts prepared with Plasma-Lyte solution were obtained from 12 patients who died 11.6 days (range up to 66 days) after operation. When compared with control veins prepared with saline and obtained at similar intervals, they had significantly more intact endothelium, less subintimal cellular infiltration, less fibrin deposition, fewer medial inflammatory changes, and less necrosis. Thus EDRF activity is significantly affected by vein graft preparation. Changes in technique to preserve EDRF produced better graft morphology early after operation.


Radiation dose reduction during intra-arterial chemotherapy for retinoblastoma: a retrospective analysis of 96 consecutive pediatric interventions using five distinct protocols.
Intra-arterial chemotherapy (IAC) represents a mainstay of retinoblastoma treatment in children. Patients with retinoblastoma are uniquely at risk for secondary malignancies and are sensitive to the ionizing effects of radiation. To retrospectively review a single institution's experience with IAC for retinoblastoma and the effect of variable intra-procedural imaging techniques on radiation exposure. Twenty-four consecutive patients, with a mean age of 30.8±16.3 months (range: 3.2-83.4 months), undergoing IAC for retinoblastoma between May 2014 and May 2020 (72 months) were included. No patients were excluded. The primary outcome was radiation exposure and secondary outcomes included technical success and procedural adverse events. Technical success was defined as catheterization of the ophthalmic or meningolacrimal artery and complete delivery of chemotherapy. Each procedure was retrospectively reviewed and categorized as one of five imaging protocol types. Protocol types were characterized by uniplanar versus multiplanar imaging and digital subtraction angiographic versus roadmap angiographic techniques. Radiation exposure, protocol utilization, the association of protocol and radiation exposure were assessed. During 96 consecutive interventions, 109 ocular treatments were performed. Thirteen of the 96 (15.5%) treatments were bilateral. Ocular technical success was 106 of 109 (97.2%). All three treatment failures were successfully repeated within a week. Mean fluoroscopy time was 6.4±6.2 min (range: 0.7-31.1 min). Mean air kerma was 36.2±52.2 mGy (range: 1.4-215.0 mGy). There were two major (1.8%) complications and four (3.7%) minor complications. Of the 96 procedures, 10 (10.4%), 9 (9.4%), 13 (13.5%), 28 (29.2%) and 36 (37.5%) were performed using protocol types A, B, C, D and E, respectively. For protocol type A, mean fluoroscopy time was 10.3±6.8 min (range: 3.0-25.4 min) and mean air kerma was 118.2±61.2 mGy (range: 24.5-167.3 mGy). For protocol type E, mean fluoroscopy time was 3.1±3.2 min (range: 0.7-15.1 min) and mean air kerma was 5.4±4.2 mGy (range: 1.4-19.5 mGy). Fluoroscopy time and air kerma decreased over time, corresponding to the reduced use of multiplanar imaging and digital subtraction angiography. In the first quartile (procedures 1-24), 8 (33.3%), 7 (29.2%), 2 (8.3%), 6 (25.0%) and 1 (4.2%) were performed using protocol types A, B, C, D and E, respectively. Mean fluoroscopy time was 10.5±8.2 min (range: 2.4-28.1 min) and mean air kerma was 84.2±71.6 mGy (range: 12.8-215.0 mGy). In the final quartile (procedures 73-96), 24 (100%) procedures were performed using protocol type E. Mean fluoroscopy time was 3.5±4.0 min (range: 0.7-15.1 min) and mean air kerma was 5.0±4.3 mGy (range: 1.4-18.0 mGy), representing 66.7% and 94.1% reductions from the first quartile, respectively. Technical success in the second half of the experience was 100%. Sequence elimination, consolidation from biplane imaging to lateral-only imaging, and replacing digital subtraction with roadmap angiography dramatically reduced radiation exposure during IAC for retinoblastoma without adversely affecting technical success or safety.


DDI-MuG: Multi-aspect graphs for drug-drug interaction extraction.
Drug-drug interaction (DDI) may lead to adverse reactions in patients, thus it is important to extract such knowledge from biomedical texts. However, previously proposed approaches typically focus on capturing sentence-aspect information while ignoring valuable knowledge concerning the whole corpus. In this paper, we propose a Multi-aspect Graph-based DDI extraction model, named DDI-MuG. We first employ a bio-specific pre-trained language model to obtain the token contextualized representations. Then we use two graphs to get syntactic information from input instance and word co-occurrence information within the entire corpus, respectively. Finally, we combine the representations of drug entities and verb tokens for the final classification. To validate the effectiveness of the proposed model, we perform extensive experiments on two widely used DDI extraction dataset, DDIExtraction-2013 and TAC 2018. It is encouraging to see that our model outperforms all twelve state-of-the-art models. In contrast to the majority of earlier models that rely on the black-box approach, our model enables visualization of crucial words and their interrelationships by utilizing edge information from two graphs. To the best of our knowledge, this is the first model that explores multi-aspect graphs to the DDI extraction task, and we hope it can establish a foundation for more robust multi-aspect works in the future.


Beneficial and detrimental aspects of miRNAs as chief players in breast cancer: A comprehensive review.
Breast cancer (BC) is the most common cancer in women and poses a serious threat to their health. Despite familiarity with factors affecting its etiology, initiation, progression, treatment strategies, and even resistance to therapy, it is considered a significant problem for women. However, several factors have greatly affected previous aspects affecting BC progression and treatment in the last decades. miRNAs are short non-coding RNA sequences that regulate gene expression by inhibiting the translation of the target mRNA. miRNAs play a crucial role in BC pathogenesis by promoting cancer stem cell (CSCs) proliferation, postponing apoptosis, continuing the cell cycle, and endorsing invasion, angiogenesis, and metastasis. Similarly, miRNAs influence important BC-related molecular pathways such as the PI3K/AKT/mTOR signaling pathway, the Wnt/β-catenin system, JAK/STAT signaling pathway, and the MAPK signaling pathway. Moreover, miRNAs affect the treatment response of BC to chemo and radiotherapy. Consequently, this review aims to provide an acquainted summary of oncomiRs and tumor suppressor (TS) miRNAs and their potential role in BC pathogenesis and therapy responses by focusing on the molecular pathways that drive them.


The relation between hypoxia and CO2-induced reflex alternation of breathing in man.
Four healthy young volunteers, selected for the responsiveness and steadiness of their breathing, were studied in rest and mild exercise while receiving alternate inspirates of low and high PCO2 (0 and 8.6 kPa). PACO2, oscillated between ca. 6 and 7.5 kPa (45-55 torr). PAO2 was held steady at 4-7 levels between 6 and 28 kPa (45-210 torr). Thirteen separate inspiratory and expiratory variables (volumes, times, flows) were recorded and tested for reflex alternation. Matched controls were performed. Responses were generally small in relation to the scatter. Reflex alternation of any one variable was not always evident. The incidences of the responses were, in descending order, inspiratory flows and volumes, expiratory flows and volumes, expiratory duration; inspiratory duration alternated seldom, and then with only small amplitude. Reflex alternation was more likely to be observed in hypoxia than in euoxia or hyperoxia. A tendency for the incidences to be greater in exercise than at rest was not significant, but the amplitudes of alternation showed a significant difference in favour of exercise. In a substantial minority of experiments the amplitude of reflex alternation was significantly and positively correlated with hypoxia (1/(PAO2--C)). Alternation also occurred frequently in another substantial minority of experiments in which, however, there was no significant amplitude-hypoxia correlation. It was concluded that these two groups probably differed not so much in the form of the amplitude-hypoxia relation as in respect of the extent of the scatter in the observations. The results are consistent with interaction of non-steady-state with steady-state signals at the arterial chemoreceptors.


Complement proteins and C3 anaphylatoxin in the tears of patients with conjunctivitis.
Previous studies in our laboratory have demonstrated pollen-specific IgG antibodies in the tears of patients with vernal conjunctivitis (VC) and elevated tear IgG levels in patients with contact lens-induced giant papillary conjunctivitis (GPC). Tear secretions were examined for complement (C) proteins to determine the role of this effector system in the pathogenesis of these ocular disorders. The tears of VC (15) and GPC (10) patients with active disease had elevated tear levels of both C3 and factor B. By use of transferrin as a marker for the leakage of plasma proteins into the tears, most C3 was locally produced by the conjunctival tissues. Although immune complexes could not be detected in the tear secretions, increased levels of C3 des Arg were present in the tears that suggested complement activation with the generation of anaphylatoxins. These studies suggest that complement may be important in the inflammatory ocular process of VC and GPC and that the generation of anaphylatoxins (C3a), even by nonimmune mechanisms, may contribute to basophil and mast cell activation with the release of inflammatory mediators into the tear secretions.


Strategies to minimize background autofluorescence in live mice during noninvasive fluorescence optical imaging.
As small-animal fluorescence imaging becomes increasingly accessible to a broad spectrum of users, many lab animal researchers are just beginning to be exposed to its challenges. One setback to fluorescence imaging is background autofluorescence generated in animal tissue and in ingested food. The authors bring this issue into focus, and show how autofluorescence can be reduced in nude mice through selection of appropriate excitation wavelength and mouse diet.


Hemispheric differences in evoked potentials to pictures of faces in the left and right visual fields.
Fifteen right-handed women evaluated the similarity of two faces presented to them either in the left or in the right visual field. The subjects' task was to decide whether the faces were the same or different and accordingly to press a button or abstain from doing so. Errors made by the subjects and the visual evoked potentials (VEPs) from points O1 and O2 referred to point CZ were recorded. Behavioural and electrophysiological results demonstrated the superiority of the right hemisphere in the perception of faces. The subjects made fewer errors when faces were presented in the left visual field. The number of errors also decreased when the presented faces were different from each other. Analysis of the VEPs indicates the existence of hemispheric asymmetry as early as 100 msec after the first stimulus disappeared. The asymmetry is larger in response to the second stimulus. On the basis of these results we conclude that differentiation in hemispheric functions takes place in the phase of short-term memory. The smaller number of errors made when the presented faces were different we explain by the strategy applied by the subjects.


Intradialytic plantar electrical nerve stimulation to improve mobility and plantar sensation among adults with diabetes undergoing hemodialysis: a randomized double-blind trial.
Impaired mobility is a debilitating consequence of hemodialysis. We examined the efficacy of intradialytic-plantar-electrical-nerve-stimulation (iPENS) to promote mobility among diabetes patients undergoing hemodialysis.. Adults with diabetes undergoing hemodialysis received either 1-h active iPENS, (Intervention-Group) or non-functional iPENS (Control-Group) during routine hemodialysis for 12 weeks (3 sessions/week). Participants and care-providers were blinded. Mobility (assessed using a validated pendant-sensor) and neuropathy (quantified by vibration-perception-threshold test) outcomes were assessed at baseline and 12 weeks. Among 77 enrolled subjects (56.2 ± 2.6 years old), 39 were randomly assigned to the intervention group, while 38 were assigned to the control group. No study-related adverse events and dropouts were reported in the intervention group. Compared to the control group, significant improvements with medium to large effect sizes were observed in the intervention group at 12 weeks for mobility-performance metrics, including active-behavior, sedentary-behavior, daily step counts, and sit-to-stand duration variability (p < 0.05), Cohen's d effect size (d = 0.63-0.84). The magnitude of improvement in active-behavior was correlated with improvement in the vibration-perception-threshold test in the intervention group (r = - 0.33, p = 0.048). A subgroup with severe-neuropathy (vibration-perception-threshold > 25 V) showed a significant reduction in plantar numbness at 12 weeks compared to baseline (p = 0.03, d = 1.1). This study supports feasibility, acceptability, and effectiveness of iPENS to improve mobility and potentially reduce plantar numbness in people with diabetes undergoing hemodialysis. Considering that exercise programs are not widely used in hemodialysis clinical practice, iPENS may serve as a practical, alternative solution to reduce hemodialysis-acquired weakness and promote mobility.


The Use of Human Wharton's Jelly Cells for Cochlear Tissue Engineering.
Tissue engineering focuses on three primary components: stem cells, biomaterials, and growth factors. Together, the combination of these components is used to regrow and repair damaged tissues that normally do not regenerate easily on their own. Much attention has been focused on the use of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), due to their broad differentiation potential. However, ESCs and iPSCs require very detailed protocols to differentiate into target tissues, which are not always successful. Furthermore, procurement of ESCs is considered ethically controversial in some regions and procurement of iPSCs requires laborious transformation of adult tissues and characterization. However, mesenchymal stem cells are an adult stem cell population that are not ethically controversial and are readily available for procurement. Furthermore, mesenchymal stem cells exhibit the ability to differentiate into a variety of cell types arising from the mesoderm. In particular, human Wharton's jelly cells (hWJCs) are mesenchymal-type stem cells found in umbilical cords that possess remarkable differentiation potential. hWJCs are a highly desirable stem cell population due to their abundance in supply, high proliferation rates, and ability to differentiate into multiple cell types arising from all three germ layers. hWJCs are used to generate several neurological phenotypes arising from the ectoderm and are considered for engineering mechanosensory hair cells found in the auditory complex. Here, we report the methods for isolating hWJCs from human umbilical cords and non-virally transfected for use in cochlear tissue engineering studies.


Percutaneous ultrasonic tenotomy effectively debrides tendons of the extensor mechanism of the knee: A technical note.
Percutaneous ultrasonic tenotomy (PUT) is a minimally-invasive method of treating patellar tendinosis, but its immediate effect on tendon structure has never been studied. Given the crucial nature of the extensor mechanism of the knee, it is important to understand the procedure's effect on tendon structure prior to clinical implementation. The aim of this study was to analyze the tendon structure of the extensor mechanism of the knee after PUT in a cadaveric model. Four fresh-frozen cadaveric specimens (two patellar and two quadriceps tendons) underwent PUT. The tendons were then sectioned and stained with hematoxilin & eosin (H&E). The sections were analyzed for a clear area of debridement. The area of debridement was calculated as an average of three measurements. All four tendons demonstrated a clear area of debridement limited to the treatment area without damaging any surrounding tissue. The area of debridement for the patellar and quadriceps tendons treated was 2.89 mm2, 1.5 mm2, 2.98 mm2 and 7.29 mm2, respectively. Percutaneous ultrasonic tenotomy effectively debrided the treatment area in all tendons without damaging surrounding tissue. Further work is needed to report clinical outcomes, assess the risk of post-procedure tendon rupture and define return-to-sport progression.


Impacts of C-uptake by plants on the spatial distribution of 14C accumulated in vegetation around a nuclear facility-Application of a sophisticated land surface 14C model to the Rokkasho reprocessing plant, Japan.
The impacts of carbon uptake by plants on the spatial distribution of radiocarbon (14C) accumulated in vegetation around a nuclear facility were investigated by numerical simulations using a sophisticated land surface 14C model (SOLVEG-II). In the simulation, SOLVEG-II was combined with a mesoscale meteorological model and an atmospheric dispersion model. The model combination was applied to simulate the transfer of 14CO2 and to assess the radiological impact of 14C accumulation in rice grains during test operations of the Rokkasho reprocessing plant (RRP), Japan, in 2007. The calculated 14C-specific activities in rice grains agreed with the observed activities in paddy fields around the RRP within a factor of four. The annual effective dose delivered from 14C in the rice grain was estimated to be less than 0.7 μSv, only 0.07% of the annual effective dose limit of 1 mSv for the public. Numerical experiments of hypothetical continuous atmospheric 14CO2 release from the RRP showed that the 14C-specific activities of rice plants at harvest differed from the annual mean activities in the air. The difference was attributed to seasonal variations in the atmospheric 14CO2 concentration and the growth of the rice plant. Accumulation of 14C in the rice plant significantly increased when 14CO2 releases were limited during daytime hours, compared with the results observed during the nighttime. These results indicated that plant growth stages and diurnal photosynthesis should be considered in predictions of the ingestion dose of 14C for long-term chronic releases and short-term diurnal releases of 14CO2, respectively.


Blood pressure-lowering efficacy of the fixed-dose combination of azilsartan medoxomil and chlorthalidone: a factorial study.
This study compared the efficacy and safety of fixed-dose combinations (FDCs) of the angiotensin II receptor blocker azilsartan medoxomil (AZL-M) and the thiazide-like diuretic chlorthalidone (CLD) with the individual monotherapies in a double-blind factorial study. A total of 1714 patients with clinic systolic blood pressure (SBP) 160 mm Hg to 190 mm Hg inclusive were randomized to AZL-M 0 mg, 20 mg, 40 mg, or 80 mg and/or chlorthalidone 0 mg, 12.5 mg, or 25 mg. The primary efficacy end point was change from baseline to 8 weeks in trough (hour 22-24) SBP by ambulatory blood pressure (BP) monitoring (ABPM). Patients' mean age was 57 years; 47% were men and 20% were black. Baseline trough BP was approximately 165/95 mm Hg and 151/91 mm Hg by clinic and ABPM measurements, respectively. For the pooled AZL-M/CLD 40/25-mg and 80/25-mg FDC groups, SBP reduction by ABPM at trough was 28.9 mm Hg and exceeded AZL-M 80 mg and CLD 25 mg monotherapies by 13.8 mm Hg and 13 mm Hg, respectively (P<.001 for both comparisons). Discontinuation rates and elevations in serum creatinine were dose-dependent and occurred more often in the AZL-M/CLD groups. In patients with stage 2 hypertension, treatment with the combination of AZL-M and CLD resulted in substantially greater SBP reduction compared with either agent alone.


Banding a hemodialysis arteriovenous fistula to decrease blood flow and resolve high output cardiac failure: report of a case.
We report herein the successful surgical treatment of a patient with high-output cardiac failure which developed from a high-flow hemodialysis arteriovenous fistula of the Brescia-Cimino type. Banding correction of the venous limb of the fistula with a woven Dacron prosthesis resulted in marked improvement of the cardiac failure. An ultrasonic study showed the fistula flow of 3.2 l/min to be as high as 40% of the resting cardiac output, or 8.0 l/min, before banding, while an intraoperative electromagnetic study was useful for controlling the degree of banding and showing the decrease of fistula flow from 3.7 l/min to 1.4 l/min.


FADS1 rs174550 genotype and high linoleic acid diet modify plasma PUFA phospholipids in a dietary intervention study.
Fatty acid desaturase 1 (FADS1) gene encodes for delta-5 desaturase enzyme which is needed in conversion of linoleic acid (LA) to arachidonic acid (AA). Recent studies have shown that response to dietary PUFAs differs between the genotypes in circulating fatty acids. However, interactions between the FADS1 genotype and dietary LA on overall metabolism have not been studied. We aimed to examine the interactions of FADS1 rs174550 genotypes (TT and CC) and high-LA diet to identify plasma metabolites that respond differentially to dietary LA according to the FADS1 genotype. A total of 59 men (TT n = 26, CC n = 33) consumed a sunflower oil supplemented diet for 4 weeks. Daily dose of 30, 40, or 50 ml was calculated based on body mass index. It resulted in 17-28 g of LA on top of the usual daily intake. Fasting plasma samples at the beginning and at the end of the intervention were analyzed with LC-MS/MS non-targeted metabolomics method. At the baseline, the carriers of FADS1 rs174550-TT genotype had higher abundance of long-chain PUFA phospholipids compared to the FADS1 rs174550-CC one. In response to the high-LA diet, LA phospholipids and long-chain acylcarnitines increased and lysophospholipids decreased in fasting plasma similarly in both genotypes. LysoPE (20:4), LysoPC (20:4), and PC (16:0_20:4) decreased and cortisol increased in the carriers of rs174550-CC genotype; however, these genotype-diet interactions were not significant after correction for multiple testing. Our findings show that both FADS1 rs174550 genotype and high-LA diet modify plasma phospholipid composition. The study was registered to ClinicalTrials: NCT02543216, September 7, 2015 (retrospectively registered).


Diurnal fluctuations of cell kinetic parameters in the epidermis and the sebaceous gland of the hamster ear.
By using the colcemid method, the presence of a diurnal variation for the mitosis index was confirmed, showing a definite minimum during the night in the sebaceous gland of the Syrian hamster ear. Furthermore, the number of all labelled cells and the quotient "single-labelled 14C-cells + double-labelled cells/single-labelled 3H-cells" determined with double-labelling autoradiography ([3H] and [14C]thymidine) seem to be subject to rhythmic fluctuations, although statistical support for this observation is lacking. The parallelism of the rhythmic variations in the epidermis and in the sebaceous glands is striking.


Parental cigarette smoking and childhood risks of hepatoblastoma: OSCC data.
Reported cigarette smoking habits for the parents of 43 UK children who died with hepatoblastoma (1953-55 deaths, 1971-81 deaths) have been compared with corresponding information for the parents of 5777 healthy control children by means of unconditional logistic regression. Hepatoblastoma risks were doubled if both parents smoked relative to neither parent smoking (RR 2.28, 95% CI 1.02-5.09).


Psilocybin containing mushrooms: a rapidly developing biotechnology industry in the psychiatry, biomedical and nutraceutical fields.
Humans have collected and used hallucinogenic mushrooms for ethnic medicinal, recreational, and religious purposes since before recorded history. Currently, the use of these mushrooms is illegal in most countries, but where their use is legal they are applied as self medication. Psilocybin and psilocin, two psychoactive alkaloids, are naturally synthesized by hallucinogenic mushrooms. The chemical structure of these compounds are similar to the neurotransmitter serotonin. Activation of this system by psilocybin and psilocin may produce temporary changes in the brain that induce hallucinations and feelings of euphoria. Adjustment of the serotonin system in this way can moderate symptoms of related mental disorders. This review summarizes relevant and current information regarding the discovery of hallucinogenic mushrooms and their contained psychoactive compounds, the events that lead to their criminalization and decriminilization, and the state of knowledge of psilocybin, psilocin, and derivatives. Last, research on the psychoactive properties of these mushrooms is placed in perspective to possible applications for human dysfunctions.


The role of BRCA2 in the fragility of interstitial telomeric sites.
We examined frequencies of radiation-induced chromosomal aberrations, using classical cytological methods, and DNA damage in interphase and metaphase cells, using a combination of FISH, CO-FISH, TIF (telomere dysfunction induced assay) and simultaneous detection of DNA damage and telomeric sequences in metaphase chromosomes, in Chinese hamster cells defective in BRCA2 and control cells. Given that the Chinese hamster genome contains large blocks of interstitial telomeric sites, our results allow us to examine the role of BRCA2 in the potential fragility of these sites, but also whether BRCA2 affects DNA repair within terminal telomeric sequences. BRCA2 defective cells exhibited greater frequencies of DNA damage within interstitial telomeric sites, as well as within terminal telomeric sites, relative to control cells. Therefore, BRCA2 deficiency contributes to the telomere dysfunction phenotype in Chinese hamster cells.


Dopamine Depletion Reduces Food-Related Reward Activity Independent of BMI.
Reward sensitivity and possible alterations in the dopaminergic-reward system are associated with obesity. We therefore aimed to investigate the influence of dopamine depletion on food-reward processing. We investigated 34 female subjects in a randomized placebo-controlled, within-subject design (body mass index (BMI)=27.0 kg/m(2) ±4.79 SD; age=28 years ±4.97 SD) using an acute phenylalanine/tyrosine depletion drink representing dopamine depletion and a balanced amino acid drink as the control condition. Brain activity was measured with functional magnetic resonance imaging during a 'wanting' and 'liking' rating of food items. Eating behavior-related traits and states were assessed on the basis of questionnaires. Dopamine depletion resulted in reduced activation in the striatum and higher activation in the superior frontal gyrus independent of BMI. Brain activity during the wanting task activated a more distributed network than during the liking task. This network included gustatory, memory, visual, reward, and frontal regions. An interaction effect of dopamine depletion and the wanting/liking task was observed in the hippocampus. The interaction with the covariate BMI was significant in motor and control regions but not in the striatum. Our results support the notion of altered brain activity in the reward and prefrontal network with blunted dopaminergic action during food-reward processing. This effect is, however, independent of BMI, which contradicts the reward-deficiency hypothesis. This hints to the hypothesis suggesting a different or more complex mechanism underlying the dopaminergic reward function in obesity.


[A systematic analysis of nosocomial outbreaks of nosocomial infections after gastrointestinal endoscopy].
Esophagogastroduodenoscopy (EGD), endoscopic retrograde cholangiopancreatography (ERCP) and colonoscopy (CLN) come with a potential risk of pathogen transmission. Unfortunately, up to now data on the causes and the distribution of pathogens is rather sparse.We performed a systematic review of the medical literature using the Worldwide Outbreak Database, the PubMed, and Embase. We then checked so-retrieved articles for potential sources of the outbreak, the spectrum of pathogens, the attack rates, mortality and infection control measures.In total 73 outbreaks (EGD: 24, ERCP: 42; CLN: 7) got included. The corresponding attack rates were 3.5%, 7.1% and 12.8% and mortality rates were 6.3%, 12.7% and 10.0% respectively. EGD was highly associated with transmission of enterobacteria including a large proportion of multi-drug resistant strains. ERCP led primarily to transmission of non-fermenting gram-negative rods. The most frequent cause was human failure during reprocessing regardless of the type of endoscope.Staff working in the field of endoscopy should always be aware of the possibility of pathogen transmission in order to detect and terminate those events at the early most time point. Furthermore, proper ongoing education of staff involved in the reprocessing and maintenance of endoscopes is crucial. Single-use devices may be an alternative option and lower the risk of pathogen transmission, but on the downside may also increase costs and waste.


Molecular cloning, characterization and expression analysis of cathepsin D gene from turbot Scophthalmus maximus.
Cathepsin D is a lysosomal endoproteolytic aspartic proteinase which also has been found in endosomes of macrophage. It is thought to play key roles in the developmental and physiological process of animals. The EST sequence of turbot (Scophthalmus maximus L.) cathepsin D was obtained from a subtractive cDNA library. In the present study, 5'-RACE and 3'-RACE were carried out to obtain the complete cDNA sequence of turbot cathepsin D, which contained a 91 bp 5'-UTR, a 1191 bp open reading frame encoding 396 amino acids, and a 329 bp 3'-UTR. The deduced amino acid sequence of the cathepsin D consisted of a signal peptide of 18 aa, a leader peptide extending 43 aa, and a mature peptide of 335 aa. BLAST analysis revealed that turbot cathepsin D shared high similarity with other known cathepsin D, and it showed significant homology with that of Barramundi (Lates calcarifer B., 89% aa similarity). Quantitative real-time PCR (q PCR) demonstrated that the highest expression level of the turbot cathepsin D was in liver. After turbot were challenged with Vibrio harveyi, the lowest expression levels of cathepsin D in liver, spleen and head kidney were detected at 8 h. This result was different from the expression of MHCII of which the expression lever was increased upon challenge. The expression levels of cathepsin D in liver and head kidney increased gradually after 8 h and exceeded the background level after 24 h. In spleen, the expression level was reinforced after 8 h and kept at level that was higher than the original level after 12 h. The results suggested that cathepsin D might process antigens for presentation to the immune system and have synergetic effect with apoptosis pathway until 12 h after injection.


T-cell engaging poly(lactic-co-glycolic acid) nanoparticles as a modular platform to induce a potent cytotoxic immunogenic response against PD-L1 overexpressing cancer.
Bispecific nanoparticles (NPs) are conjugated with two antibodies that enhance T cell cytotoxicity by sequentially targeting CD3 and tumor-specific proteins. This interaction redirects T cells to specific tumor antigens and activates them to lyse tumor cells by blocking two different signaling pathways simultaneously. This study developed NP-based bispecific T-cell engagers (nanoBiTEs), which are R848-loaded bispecific poly(lactic-co-glycolic acid) NPs decorated with anti-CD3 antibody targeting T cells and anti-PD-L1 antibody targeting PD-L1 ligands (bis-R848-PLGA-NPs). Bis-R848-PLGA-NPs enhance the immunogenic response in destroying cancer cells by restoring the T cell effector functions. These interactions allow T cells to come in close proximity to the tumor cells. Finally, the release of R848 from PLGA-NPs activates dendritic cells, enhancing T cell activation. In vitro results show maximum internalization of bis-R848-PLGA-NPs in SK-OV3 and B16F10 cell lines, attributed to high PD-L1 expression in both cells. Furthermore, bis-R848-PLGA-NPs-treated CD8+ T cells exhibit a significantly increased total amount of CD8+/CD25+, CD8+/CD69+, and cytokine expression that leads to the robust inhibition of PD-L1 expressed cancer cells. Additionally, tumor growth is significantly inhibited by bis-R848-PLGA-NPs in the B16F10 xenograft mouse model and significantly enhanced intratumoral infiltration of CD4+ and CD8+ T cells, as well as tumor-infiltrated cytokines.


Maternal and fetal brain contents of docosahexaenoic acid (DHA) and arachidonic acid (AA) at various essential fatty acid (EFA), DHA and AA dietary intakes during pregnancy in mice.
We investigated essential fatty acids (EFA) and long-chain polyunsaturated fatty acids (LCP) in maternal and fetal brain as a function of EFA/LCP availability to the feto-maternal unit in mice. Diets varying in parent EFA, arachidonic acid (AA), and docosahexaenoic acid (DHA) were administered from day 3 prior to conception till day 15 of pregnancy. We concentrated on DHA, AA, Mead acid, and EFA-index [(omega-3+omega-6)/(omega-7+omega-9)] in maternal erythrocytes, maternal brain, and fetal brain. It was found that erythrocyte EFA/LCP sensitively reflects declining EFA/LCP status in pregnancy, although this decline was not apparent in maternal brain. Differences in erythrocyte EFA/LCP coincided with larger differences in fetal brain EFA/LCP as compared to EFA/LCP in maternal brain. Both maternal and fetal brains were affected by short-term EFA/LCP intake, but the developing fetal brain proved most sensitive. The inverse relationship between fetal brain AA and DHA suggests the need of a maternal dietary DHA/AA balance, at least in mice.


Laser Fenestration in TEVAR: Perspectives and Future Directions.
Endovascular aortic repair has been increasingly used to treat a multitude of thoracic aorticpathologies. When placement of a thoracic endograft necessitates coverage of one or more of the great vessels, in situ laser fenestration is a safe and effective option for supra-aortic trunk revascularization. Certain anatomic factors may render laser fenestration more technically challenging, particularly depending on aortic arch type and branch vessel characteristics. Short-term and mid-term outcomes have shown promising results for mortality, stroke, and complication rates. Future developments may extend the utility of this approach and allow it to be applied to a more widespread set of patients with challenging anatomy.


Early experience with uniportal robotic thoracic surgery lobectomy.
Invasiveness is considered one of the cornerstones of every field of surgery, and video-assisted thoracoscopic (VATS) approaches are now routinely used worldwide to perform pulmonary resections. Recently, robotic-assisted thoracic surgery (RATS) has become the preferred technique in many centers; it is routinely performed using three or four ports with at least one service incision, contrasting with the real concept of invasiveness, especially when compared to uniportal VATS (U-VATS). Hereby, we present our early experience with uniportal RATS (U-RATS) pulmonary resections for early-stage lung cancer. Technical details of surgical steps are accurately described and commented on. Twenty-four consecutive patients with lung cancer underwent U-RATS anatomical pulmonary resections at our institute. All procedures were completed with the uniportal approach. The mean operative time was 210 min (range 120-350); in the last 10 cases, the operative time was significantly reduced (180 min) compared to the first 10 cases (232 min) (p < 0.02), showing a very fast learning curve. The postoperative pain score was comparable to that for U-VATS and was constantly low. U-RATS is a safe and feasible technique, combining the advantages of U-VATS with the well-known advantages of robotic surgery.


Characterization of the nuclear localization signal in the avian sarcoma virus integrase.
A sequence of 21 amino acids (aa) in the C-terminal region of the 286-aa avian sarcoma virus (ASV) integrase (IN) protein has been shown previously to mediate nuclear localization of both IN and beta-galactosidase (betaGal) protein fused to it. This karyophilic sequence includes a high proportion of prolines and residues with basic side chains. In this report, site-directed mutagenesis was used to introduce single aa substitutions of several of these residues. Indirect immunofluorescence showed that IN-betaGal fusion constructs with Ala substitutions for sequence constituents K206, P215, K225 or R227 had lost the exclusive nuclear localization capability of the wild-type fusion. A fusion protein with the conservative substitution K206R retained the nuclear localization capacity. The site-specific substitutions that reduced karyophilic activity had no effect on the processing or joining activities of IN in vitro. However, the introduction of three of the four Ala codon substitutions into viral DNA clones caused a significant delay in viral replication following transfection of cycling chicken embryo fibroblasts. These results are consistent with a possible role for ASV IN in nuclear targeting.


Neurobehavioral effects of tetramisole in mice.
Acute toxicity and neurobehavioral effects of the veterinary anthelmintic tetramisole were examined in male albino mice. The 24-h median lethal doses of tetramisole were determined by the up-and-down method in mice after oral, subcutaneous and intraperitoneal administrations, and they were 110, 57 and 34 mg/kg, respectively. The intoxicated mice manifested nervousness, crouching, piloerection and tremor. Subcutaneous injection of tetramisole at 0.5 and 1mg/kg did not significantly affect general locomotor activity of the mice in 5-min open-field activity test or negative geotaxis performance and landing foot splay. However, the 1mg/kg dose of tetramisole significantly increased the stereotyped behavior (grooming, sniffing, biting and licking and head bobbing) of the mice when compared to the control group. Daily treatment of mice with tetramisole at 0.5 and 1mg/kg for six consecutive days did not significantly affect their general locomotor activity in the open-field activity test. Both doses of tetramisole significantly increased stereotyped behavior of the mice on days 3, 5 and 8 in comparison with respective control values. Repeated tetramisole treatments (0.5 and 1mg/kg) also significantly decreased the time needed to complete the negative geotaxis task and reduced landing foot splay. All tetramisole-treated mice showed crouching behavior and were nervous and difficult to handle. The results suggest nervous involvement in the acute toxicity of tetramisole. Stereotyped behavior and changes in the negative geotaxis and landing foot splay are reported for the first time in mice treated with tetramisole.


Lexical guidance in sentence processing: a note on Adams, Clifton, and Mitchell (1998).
Mitchell (1987) conducted a self-paced reading experiment that showed that people experienced difficulty reading a noun phrase when it immediately followed an intransitive verb. From this, he argued for a two-stage theory of parsing, in which verb subcategorization information is initially ignored. In response, Adams, Clifton, and Mitchell (1998) found no evidence to support this claim in an eye-tracking experiment and argued that Mitchell's segmentation procedure distorted the parsing process. We report an eye-tracking experiment, in which materials similar to those in Adams et al., but with longer noun phrases, were used, that showed a pattern of difficulty similar to Mitchell's findings. Hence, Mitchell's results did not depend on the use of an artificial method of presentation. The results cast further doubt on the adequacy of constraint-based accounts of parsing.


Molecular and morphometric analysis of the rat ventral prostate injected with leptin.
The aim of this study was to evaluate the effect of leptin administration on the ventral prostate lobe of adult rat. Twenty adult male rats were divided into 2 groups: L-animals were daily injected with 50 μL of leptin (8 μg/100 g BW, subcutaneous) for four days and C-animals received the same volume of saline solution. Lipid profile and testosterone serum levels were evaluated. The prostate ventral lobe was processed for histomorphometric analysis. Gene expression of aromatase, androgen, leptin and estrogen receptors isoforms was evaluated by real-time PCR. Cell proliferation was evaluated by PCNA immunohistochemistry. Data were expressed as mean±standard error and analyzed by student's t-test. Serum levels of cholesterol (C=39.7±4.2;L=55.2±4.2, mg/dL; P<0.02) increased and testosterone (C=1.6±0.43;L=0.6±0.15, ng/dL; P<0.03) decreased in L group. The histomorphometric analysis showed a reduction in cell density (C=8868±242; L=8211±210, mm(2); P<0.04), in total (C=0.24±0.026; L=0.10±0.009, mm(2); P<0.001) and in the internal acini areas (C=0.16±0.009; L=0.08±0.006, mm(2); P<0.0002). On the other hand, there was an increase in the epithelial height (C=17.3±0.3; L=22.8±0.2, μm; P<0.0001) and in the number of acini (C=7.0±0.2; L=8.7±0.1, mm(2); P<0.0002). The histomorphometric analyses together with PCNA immunohistochemistry results suggest that leptin increases cell proliferation. In relation to the gene expression, leptin treatment increased the expression of all genes, but ER-α, in more than 200 times compared to the expression in C group. In conclusion, in this paper we showed that leptin has a direct effect on the prostate gland of adult rats leading to an increase in proliferation and in the gene expression of aromatase, androgen, leptin and estrogen receptors isoforms that are important for the physiology of the prostate gland.


9. Steroid receptors. Correlation of estrogen and progesterone receptor status with ultrastructural differentiation in breast tumors.
The interrelationships of ultrastructural and biochemical parameters have been studied in a multivariate analysis of 139 cases of invasive breast carcinoma. There was no relationship between the histologic subclassification and distribution of estrogen and progesterone receptors. However, significant correlations could be found between receptor status and certain ultrastructural features of the tumor cells. A prevalence of well differentiated cancers had a significant correlation with a positive estrogen receptor status. Estrogen receptors were more frequently associated to tumors showing great complexity of cytoplasmic organization, high degrees of cell interconnections by desmosomes and membrane interdigitations, presence of intracytoplasmic ductules, specific secretory granules, and low grades of nuclear pleomorphy. In a series of 120 non-selected cases, receptor status was assessed by the fluorescent technique. Of the cases, 38.3% have proved to be ER+, 49.2% showed low binding capacity and 12.5% were negative. The correlation of receptor content with the histological type of breast cancer revealed some type-dependent connections. While only 36.9% of the solid tumors were receptor positive the proportion increased to 54.2% for the more differentiated glandular type of ductal carcinoma. 8 out of 13 (61.5%) infiltrating lobular carcinomas and 4 (4) colloid cancers were found to be receptor positive. The plotting test showed a good correlation of histochemical receptor status and histological grading. Although the type of "receptor", which is localized by the indirect fluorescent technique is still incompletely defined, there is no doubt, that the selective binding affinity reflects a specific capacity of the tumor cells depending on their degree of differentiation.


[Reliability of skin paddle in monitoring blood flow after free fibular osteocutaneous composite flap transfer].
To evaluate the reliability of skin paddle in monitoring blood flow after free fibular osteocutaneous composite flap transfer. Seven hundred and fourteen consecutive cases of mandibular or maxillary reconstruction using free fibular flap from May 1999 to September 2007 were reviewed. The cases with postoperative vessel thrombosis were analyzed. Postoperative vessel thrombosis occurred in 23 cases, 17 were venous and 6 arterial. Among 14 cases of venous thrombosis with color change of skin paddles, only 6 were successfully salvaged, but 3 cases with no color change of skin paddles were all successfully salvaged. For arterial thrombosis, only one flap was successfully salvaged. The postoperative vessel thrombosis rate was 3.2%, and the salvage rate was 43.5%. The overall successful rate of free fibula flap was 98.2%. Postoperative vessel thrombosis can not be detected in the early stage if only observing the color change of skin paddle after free fibula flap transfer.


Nonarteritic anterior ischemic optic neuropathy: associations with homozygosity for the C677T methylenetetrahydrofolate reductase mutation.
The association between nonarteritic anterior ischemic optic neuropathy (NAION) and coagulation disorders was prospectively assessed at least 3 months after the occurrence of ocular vascular events in 12 white patients in an outpatient clinical research center. Two community-based ophthalmologists evaluated the 12 NAION patients in the consecutive order of their referral. Polymerase chain reaction-complementary DNA assays of gene mutations associated with coagulation disorders and serologic coagulation measurements in study patients were compared with those in 36 healthy, normal race-, sex-, and age-matched controls, with 3 controls matched for each case. Of the 12 patients, 4 men and 8 women (mean age 62 +/- 15 years, 3 of them 55 years or older), 8 had unilateral NAION (bilateral in 4). The 12 patients with NAION were more likely than controls to demonstrate homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation (50% vs 11 %; Fisher's P =.009, with the likelihood of a type I error quite small, 0.9%). Our sample size had a power of 80% to detect this case-control difference in C677T MTHFR homozygosity at an alpha value of.05. Of the 12 NAION patients, 7 (58%) had at least 1 gene mutation in the C677T MTHFR, G1691A V Leiden, or G20210A prothrombin gene, compared with 5 of 36 controls (14%) (chi(2) = 9.48, P =. 002, with the likelihood of a type I error quite small, 0.2%). Our sample size had a power of 85% to detect this case-control difference at alpha =. 05. Of the 8 women with NAION, 5 (63%) first experienced the condition while taking hormone replacement therapy (n = 4) or during pregnancy (n = 1), with superposition of estrogen-induced thrombophilia on heritable thrombophilia and hypofibrinolysis. Confirmation of a causal relationship between coagulation disorders and NAION should facilitate its prevention and treatment and help protect against thrombi in other vascular beds.


Body cell mass is a useful parameter for assessing malnutrition and severity of disease in non-ascitic cirrhotic patients with hepatocellular carcinoma or esophageal varices.
Body cell mass (BCM) is a nutritional parameter, however, changes in BCM in patients with non-ascitic liver cirrhosis (LC) in comparison to patients with other malnutritional diseases remains unclear. We investigated the difference in BCM between patients with LC and malnourished gastrointestinal disease controls (M.CON), and examined the relationship between BCM and the severity of LC. Results demonstrated that serum nutritional parameters were not significantly different between the LC (n=56) and M.CON groups (n=25), whereas BCM%BW was significantly lower in the LC group than in the M.CON group (50.9+/-4.6 vs. 54.4+/-7.1%, P=0.018). Furthermore, BCM%BW negatively correlated with the model for end-stage liver disease (MELD) score (P=0.04). In concluson, BCM showed a significant decrease and a negative correlation with the MELD score in the LC group. BCM may be a useful parameter for assessing malnutrition and severity of LC.


Pathways between verbal bullying and oral conditions among school children.
To investigate the direct and indirect pathways between verbal bullying and adverse oral conditions among school-aged children. A cross-sectional survey was conducted with 8- to 10-year-old children, enrolled in public schools in Southern Brazil. Verbal bullying was collected by self-reports. Independent variables included sociodemographic characteristics (sex, age, household income, and caregivers' educational level) and oral conditions (anterior open bite, anterior teeth crowding, upper anterior diastema, large overjet, untreated dental caries, and PUFA index). The pathways between verbal bullying and the independent variables were analysed through structural equation modelling. 1369 children were included. The prevalence of verbal bullying was 26.2% (95% confidence interval [CI] 23.9-28.6%). Verbal bullying was directly influenced by large overjet (standard coefficient [SC] 0.13, P < 0.01), untreated dental caries (SC 0.63, P = 0.01) and PUFA index (SC 0.75, P = 0.02). Sex (SC - 0.005, P = .04) and age (SC - 0.006, P < 0.01) indirectly influenced verbal bullying via untreated dental caries. Verbal bullying was directly influenced by large overjet, untreated dental caries and PUFA index. Sex and age indirectly impacted verbal bullying through untreated dental caries.


Enhancement of bleomycin-mediated DNA damage by epidermal microsomal enzymes.
The role of epidermal microsomal enzymes in catalyzing bleomycin-mediated chain breakage in calf-thymus DNA and in DNA isolated from neonatal rat epidermis was studied. Aerobic incubation of bleomycin with epidermal microsomes, epidermal or calf-thymus DNA and NADPH caused substantial chain breakage of the DNA which was dependent upon concentrations of drug, microsomal protein and NADPH. The reactive oxygen scavenger superoxide dismutase, the metal chelator EDTA, and cytochrome c each inhibited the enzyme-mediated chain breakage reaction. Scavengers of hydrogen peroxide and hydroxyl radicals, including catalase and benzoate and inhibitors of microsomal cytochrome P-450-dependent monooxygenases such as 1-benzylimidazole, metyrapone and alpha-naphthoflavone, had no inhibitory effects on bleomycin-mediated DNA chain breakage. In contrast, ascorbic acid significantly enhanced DNA damage by bleomycin. These studies indicate that mammalian epidermis possesses membrane-bound enzyme activity capable of enhancing bleomycin-mediated chain breakage of DNA and that oxidation/reduction of adventitious iron and generation of reactive oxygen participate in the reaction. These responses in the epidermis could directly relate to the mechanism of action of intralesional injections of bleomycin which are used quite effectively in the management of recalcitrant human warts. Either epidermal or wart virus DNA or both could be targets for this pharmacologic effect of the drug which is augmented by epidermal microsomal enzymes.


Synthesis of N-aminophalimides derived from α-amino acids: Theoretical study to find them as HDAC8 inhibitors by docking simulations and in vitro assays.
Phthalimides are valuable for synthesis and biological properties. New acetamides 3(a-c) and 4(a-c) were synthesized and characterized as precursors for novel N-aminophalimides 5(a-c) and 6(a-c). Structures of 4a, 5(a-b), and 6(a-b) were confirmed by single crystal X-ray. Docking studies identified compounds with favorable Gibbs free energy values for binding to histone deacetylase 8 (HDAC8), an enzyme targeted for anticancer drug development. These compounds bound to both the orthosteric and allosteric pockets of HDAC8, similar to Trichostatin A (TSA), an HDAC8 inhibitor. 6(a-c) contain hydroxyacetamide moiety as a zinc-binding group, a phthalimide moiety as a capping group, and aminoacetamide moiety as a linker group, which are important for ligand-receptor binding. ΔG values indicated that compounds 5b, 6b, and 6c had higher affinity for HDAC8 in the allosteric pocket compared to TSA. In vitro evaluation of inhibitory activities on HDAC8 revealed that compounds 3(a-c) and 5(a-c) showed similar inhibitory effects (IC50 ) ranging from 0.445 to 0.751 μM. Compounds 6(a-c) showed better affinity, with 6a (IC50 = 28 nM) and 6b (IC50 = 0.18 μM) showing potent inhibitory effects slightly lower than TSA (IC50 = 26 nM). These findings suggest that the studied compounds hold promise as potential candidates for further biological investigations.


Life cycle assessment and carbon reduction potential prediction of electric vehicles batteries.
Electric vehicles (EVs) battery is a crucial component of energy storage components for electric vehicles. However, the environmental impact of EVs battery is still not clear. Therefore, this paper establishes a cradle-to-cradle life cycle assessment (LCA) frame and clarifies the environmental impacts on the entire lifespan of EVs battery in China. Specifically, the environmental impact of battery production, battery use, and recycling & disposal stages are analyzed and measured. In addition, the carbon reduction potential of recycling and secondary use under a future electricity mix is estimated. Results show that: (1) The production stage of EVs battery with the carbon emission of 105 kgCO2-eq/kWh, which has the most significant impact on the environment. (2) In the recycling process, cascade utilization can reduce 1.536 kgCO2-eq/kWh carbon emission. In terms of recycling methods, hydrometallurgy can reduce the most carbon emission (13.3 kgCO2-eq/kWh), followed by the combined hydro-pyrometallurgical process (8.11 kgCO2-eq/kWh) and pyrometallurgy (0.57 kgCO2-eq/kWh). (3) Under the estimated electricity mix in 2030, 2040, and 2050, the carbon emission in battery production can be approximately reduced by 31.9 %, 45 %, and 48.1 %, respectively.


Allergen-induced IgE-dependent gut inflammation in a human PBMC-engrafted murine model of allergy.
Humanized murine models comprise a new tool to analyze novel therapeutic strategies for allergic diseases of the intestine. In this study we developed a human PBMC-engrafted murine model of allergen-driven gut inflammation and analyzed the underlying immunologic mechanisms. Nonobese diabetic (NOD)-scid-γc(-/-) mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or not. Three weeks later, mice were challenged with the allergen orally or rectally, and gut inflammation was monitored with a high-resolution video miniendoscopic system, as well as histologically. Using the aeroallergens birch or grass pollen as model allergens and, for some donors, also hazelnut allergen, we show that allergen-specific human IgE in murine sera and allergen-specific proliferation and cytokine production of human CD4(+) T cells recovered from spleens after 3 weeks could only be measured in mice treated with PBMCs plus allergen. Importantly, these mice had the highest endoscopic scores evaluating translucent structure, granularity, fibrin, vascularity, and stool after oral or rectal allergen challenge and a strong histologic inflammation of the colon. Analyzing the underlying mechanisms, we demonstrate that allergen-associated colitis was dependent on IgE, human IgE receptor-expressing effector cells, and the mediators histamine and platelet-activating factor. These results demonstrate that allergic gut inflammation can be induced in human PBMC-engrafted mice, allowing the investigation of pathophysiologic mechanisms of allergic diseases of the intestine and evaluation of therapeutic interventions.


Partial molar volumes and adiabatic compressibilities of unfolded protein states.
We determined the partial molar volumes, V degrees , and adiabatic compressibilities, K degrees (S), of N-acetyl amino acids with neutralized carboxyl termini, N-acetyl amino acid amides, and N-acetyl amino acid methylamides between 18 and 55 degrees C. The individual compounds in the three classes have been selected so as to collectively cover the 20 naturally occurring amino acid side chains. We interpret our experimental results in terms of the volumetric contributions and hydration properties of individual amino acid side chains and their constituent atomic groups. We also conducted pH-dependent densimetric and acoustic measurements to determine changes in volume and compressibility accompanying protonation of the aspartic acid, glutamic acid, histidine, lysine, and arginine side chains. We use our resulting data to develop an additive scheme for calculating the partial molar (specific) volume and adiabatic compressibility of fully extended polypeptide chains as a function of pH and temperature. We discuss the differences and similarities between our proposed scheme and the reported additive approaches. We compare our calculated volumetric characteristics of the fully extended conformations of apocytochrome c and apomyoglobin with the experimental values measured in water (for apocytochrome c) or acidic pH (for apomyoglobin). At these respective experimental conditions, the two proteins are unfolded. However, the comparison between the calculated and experimental volumetric characteristics suggests that neither apocytochrome c nor apomyoglobin are fully unfolded and retain a sizeable core of solvent-inaccessible groups.


Determination of the stereoisomers of hydroxychloroquine and its major metabolites in plasma and urine following a single oral administration of racemic hydroxychloroquine.
Plaquenil (hydroxychloroquine, HCQ; Sanofi Winthrop Pharmaceuticals, New York, NY) is a stereoisomeric drug administered as a racemic (50: 50) mixture of two isomeric forms--(+) and (-) HCQ. To correlate clinical efficiency accurately with dose, it is necessary to determine the fate of both isomers. This will allow for the optimization of clinical dosing. A method has been developed for the quantitation of (+) and (-) HCQ and its major metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), in plasma and in urine. Application of this method in a preliminary study in four human volunteers is reported. After a single oral dose of 200 mg of Plaquenil, the average enantiomeric ratio of (+) to (-) HCQ was approximately 1 over an 8-hour period. However, the average cumulative 48-hour excretion of HCQ, DHCQ, and DCQ showed stereoselective excretion.


Assessing the role of an artificial intelligence assessment tool for thoracic aorta diameter on routine chest CT.
To assess the diagnostic accuracy and clinical impact of automated artificial intelligence (AI) measurement of thoracic aorta diameter on routine chest CT. A single-centre retrospective study involving three cohorts. 210 consecutive ECG-gated CT aorta scans (mean age 75 ± 13) underwent automated analysis (AI-Rad Companion Chest CT, Siemens) and were compared to a reference standard of specialist cardiothoracic radiologists for accuracy measuring aortic diameter. A repeated measures analysis tested reporting consistency in a second cohort (29 patients, mean age 61 ± 17) of immediate sequential pre-contrast and contrast CT aorta acquisitions. Potential clinical impact was assessed in a third cohort of 197 routine CT chests (mean age 66 ± 15) to document potential clinical impact. AI analysis produced a full report in 387/436 (89%) and a partial report in 421/436 (97%). Manual vs AI agreement was good to excellent (ICC 0.76-0.92). Repeated measures analysis of expert and AI reports for the ascending aorta were moderate to good (ICC 0.57-0.88). AI diagnostic performance crossed the threshold for maximally accepted limits of agreement (>5 mm) at the aortic root on ECG-gated CTs. AI newly identified aortic dilatation in 27% of patients on routine thoracic imaging with a specificity of 99% and sensitivity of 77%. AI has good agreement with expert readers at the mid-ascending aorta and has high specificity, but low sensitivity, at detecting dilated aortas on non-dedicated chest CTs. An AI tool may improve the detection of previously unknown thoracic aorta dilatation on chest CTs vs current routine reporting.


Analytical and Clinical Evaluation of the Automated Elecsys Anti-SARS-CoV-2 Antibody Assay on the Roche cobas e602 Analyzer.
To evaluate the analytical and clinical performance of the automated Elecsys anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody (Elecsys Ab) assay on the Roche cobas e602 analyzer. With the ongoing global coronavirus disease 2019 (COVID-19) pandemic, widespread and routine serologic testing of SARS-CoV-2 remains a pressing need. To better understand its epidemiologic spread and to support policies aimed at curtailing further infections, reliable serologic testing is crucial for providing insight into the dynamics of the spread of COVID-19 on a population level. The presence of anti-SARS-CoV-2 antibodies in polymerase chain reaction-positive, confirmed COVID-19 patient samples was determined using the Elecsys Ab assay on the Roche cobas e602 analyzer. The precision and cross-reactivity of the Elecsys Ab assay were characterized and its performance was compared against the EuroImmun IgA/IgG antibody (EuroImmun Ab) assay. Calculated sensitivity, specificity, and positive and negative predictive values were assessed. The Elecsys Ab assay demonstrated good precision, had no cross-reactivity with other viral samples, and showed 100% concordance with the EuroImmun Ab assay. Excellent clinical performance with respect to sensitivity, specificity, and positive and negative predictive values was observed. The Elecsys Ab assay is a precise and highly reliable automated platform for clinical detection of seropositivity in SARS-CoV-2 infection.


The ATP costs and time required to degrade ubiquitinated proteins by the 26 S proteasome.
The degradation of ubiquitinated proteins by 26 S proteasomes requires ATP hydrolysis. To investigate if the six proteasomal ATPases function independently or in a cyclic manner, as proposed recently, we used yeast mutants that prevent ATP binding to Rpt3, Rpt5, or Rpt6. Although proteasomes contain six ATPase subunits, each of these single mutations caused a 66% reduction in basal ATP hydrolysis, and each blocked completely the 2-3-fold stimulation of ATPase activity induced by ubiquitinated substrates. Therefore, the ATPase subunits must function in a ordered manner, in which each is required for the stimulation of ATPase activity by substrates. Although ATP is essential for multiple steps in proteasome function, when the rate of ATP hydrolysis was reduced incrementally, the degradation of Ub5-DHFR (where Ub is ubiquitin and DHFR is dihydrofolate reductase) decreased exactly in parallel. This direct proportionality implies that a specific number of ATPs is consumed in degrading a ubiquitinated protein. When the ubiquitinated DHFR was more tightly folded (upon addition of the ligand folate), the rate of ATP hydrolysis was unchanged, but the time to degrade a Ub5-DHFR molecule (∼13 s) and the energy expenditure (50-80 ATPs/Ub5-DHFR) both increased by 2-fold. With a mutation in the ATPase C terminus that reduced gate opening into the 20 S proteasome, the energy costs and time required for conjugate degradation also increased. Thus, different ubiquitin conjugates activate similarly the ATPase subunit cycle that drives proteolysis, but polypeptide structure determines the time required for degradation and thus the energy cost.


Ketamine as adjunct to midazolam treatment following soman-induced status epilepticus reduces seizure severity, epileptogenesis, and brain pathology in plasma carboxylesterase knockout mice.
Delayed treatment of cholinergic seizure results in benzodiazepine-refractory status epilepticus (SE) that is thought, at least in part, to result from maladaptive trafficking of N-methyl-d-aspartate (NMDA) and gamma-aminobutyric acid type A (GABAA) receptors, the effects of which may be ameliorated by combination therapy with the NMDA receptor antagonist ketamine. Our objective was to establish whether ketamine and midazolam dual therapy would improve outcome over midazolam monotherapy following soman (GD) exposure when evaluated in a mouse model that, similar to humans, lacks plasma carboxylesterase, greatly reducing endogenous scavenging of GD. In the current study, continuous cortical electroencephalographic activity was evaluated in male and female plasma carboxylesterase knockout mice exposed to a seizure-inducing dose of GD and treated with midazolam or with midazolam and ketamine combination at 40 min after seizure onset. Ketamine and midazolam combination reduced GD-induced lethality, seizure severity, and the number of mice that developed spontaneous recurrent seizure (SRS) compared with midazolam monotherapy. In addition, ketamine-midazolam combination treatment reduced GD-induced neuronal degeneration and microgliosis. These results support that combination of antiepileptic drug therapies aimed at correcting the maladaptive GABAA and NMDA receptor trafficking reduces the detrimental effects of GD exposure. Ketamine may be a beneficial adjunct to midazolam in reducing the epileptogenesis and neuroanatomical damage that follows nerve agent exposure and pharmacoresistant SE.


Preparation and characterisation of solid state forms of paracetamol-O-glucuronide.
The synthesis and crystallisation of the pharmaceutically important metabolite, paracetamol-O-glucuronide, is described. Hydrated and anhydrous forms of the target molecule have been characterised by PXRD, DSC and TGA. In addition, a methanol solvate has been analysed, including single crystal analysis, which represents the first structure solution for this system.


A course in nursing consultation. Promoting indirect nursing activities.
Skills in consultation are a core competency for nurses practicing in advanced roles. Although changes in the healthcare delivery system are creating a growing need and increasing opportunities for nurses to provide consultation services, nurse educators have been slow to respond to the need for students to have formal education in consultation concepts and processes. The author describes a graduate-level course in nursing consultation. Suggestions are given for incorporating consultation content into other courses at both the graduate and undergraduate level.


Synergistic combination of antioxidants, silver nanoparticles and chitosan in a nanoparticle based formulation: Characterization and cytotoxic effect on MCF-7 breast cancer cell lines.
Chitosan (Cs) is a biocompatible, biodegradable cationic polymer having the ability of targeted drug delivery. Vitamin E and C are not synthesized in our body thus, when encapsulated within a carrier system these vitamins in combination with/alone can be utilized for their anti-cancer potentials. The present investigation was conducted to develop a stable nanoparticle based formulation encapsulating antioxidants (Vitamin E, catechol) and silver nanoparticles synthesized from Hibiscus rosa-sinensis (HRS) petal extracts within a chitosan matrix. The prepared nanoformulations were characterized using Field emission scanning electron microscopy (Fe-SEM), X-ray diffraction (XRD) and Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR-FTIR). They were further tested for their antioxidant potentials using DPPH assay, hydrogen peroxide scavenging assay, nitric oxide scavenging assay and ferrous antioxidant reducing potential assay. The nanoformulations were found to be highly hemocompatible and showed high encapsulation efficiency up to 76%. They also showed higher antioxidant activity than their base materials. Further, their anti-cancer efficacy was observed against MCF-7 breast cancer cells having IC50 values of 53.36±0.36μg/mL (chitosan-ascorbic acid-glucose), 55.28±0.85μg/mL (chitosan-Vitamin E), 63.72±0.27μg/mL (Chitosan-catechol) and 58.53±0.55μg/mL (chitosan-silver nanoparticles). Thus, the prepared formulations can be therapeutically applied for effective and targeted delivery in breast cancer treatment.


Selenium status prior to and during one month total parenteral nutrition in gastroenterological patients: A randomised study of two dosages of Se supplementation.
13 consecutive adult gastroenterological patients with non-malignant disease who were candidates for total parenteral nutrition (TPN), and who had mild protein-energy malnutrition (82 +/- 3% of ideal body weight, serum albumin 32 +/- 2 g/l, mean +/- SEM) were found to have, prior to TPN, a Selenium level 50% less than controls (p < 0.001) as assayed by Se and glutathione peroxidase (GSHPx) in plasma and erythrocytes. Compared with other trace metals and minerals, eg, Mn, Zn and Cu, depletion of Selenium was the most marked in this population. Patients were randomised to be supplemented with either 100 or 200 microg/d of sodium-selenite, equal to 32 microg (0.4 micromol) or 64 microg (0.8 micromol) of selenium, in two cross-over periods of TPN, each of two weeks. In this short term study, significant increases in the four measurements of Se status (p < 0.05) were seen in all patients, but there was no difference between those receiving the high or low dose of the element. GSHPx in plasma was normalised within 1 month whereas the increase seen in the erythrocyte pool was consistent with a 4-month half-life. Pooled Se values for patients and controls showed logarithmic correlations between Se and GSHPx in erythrocytes (p < 0.001) and plasma (p < 0.01). Changes in GSHPx provided further evidence of Se depletion in our patients. This study suggests that malnourished gastroenterological patients receiving TPN require Se supplements and that 100 microg (0.4 micromol)/d of sodium-selenite is adequate for most patients since there was no additional benefit from the higher dose of 200 microg (0.8 micromol).


Evidence-based medicine concerning efficacy of vaccination against Clostridium chauvoei infection in cattle.
Clostridium chauvoei infections occur frequently in cattle and produce disease end lethality. Vaccination is frequently used to prevent occurrence of these infections. Although the literature on blackleg is voluminous, scientific evidence on the efficacy of vaccination against C chauvoei to prevent diseases and lethality in cattle is scant. This study demonstrates that the evidence of efficacy of C chauvoei vaccines to prevent infection by this microorganism in cattle is poor to moderate. A greater participation of practitioners in clinical research and greater access to informational tools such as systematic reviews must be part of the objectives of veterinary medicine.


Laser Doppler measurements of the effect of panretinal photocoagulation on retinal blood flow.
The laser Doppler technique was used to measure the pulsatile characteristics of the retinal arterial blood flow in diabetic patients with severe retinopathy immediately before argon laser panretinal photocoagulation (PRP) and again one to two months after PRP. In each measurement the relative variation of the maximum red blood cell velocity, Vmax, in a major branch retinal artery was determined throughout the cardiac cycle. Flow pulsatility was defined as the ratio of Vmax at maximum systole to Vmax at minimum diastole. Following PRP, each eye showed a decrease in flow pulsatility as well as a decrease in retinal arterial and venous diameters. The measurements are consistent with an autoregulatory response of the retinal circulation to increased inner retinal oxygen concentration following PRP. Laser Doppler measurements may be a useful means of assessing the effectiveness of a particular PRP treatment.


"Confronted with paperwork": information and documentation in peer support.
Peer support has a unique philosophy of practice, which is reflected in the way information is handled. To describe the way peer supporters use documentation in their work and explore tensions this generates. Qualitative study based on two individual or group interviews with each of 37 peer supporters and peer-support managers in Aotearoa New Zealand. Peer supporters challenged disciplinary uses of documentation by either keeping minimal information about their interactions with peers, or keeping notes in a collaborative, empowering and transparent manner. This generated tensions with regard to the wider mental health system, particularly in relation to an emerging national database of mental health service use. Funders and planners need to be aware of the reasons for some peer-support services' reluctance to participate in mental health information strategies. Peer-support documentation approaches might usefully be adopted across the mental health sector.


Malaria and pre-eclampsia in an area with unstable malaria transmission in Central Sudan.
Placental malaria and pre-eclampsia occur frequently in women in tropics and are leading causes of maternal and perinatal morbidities and mortality. Few data exist concerning the interaction between placental malaria and pre-eclampsia. A case control study was conducted in Medani Hospital, which locates in an area of unstable malaria transmission in Central Sudan. Case (N = 143) were women with pre-eclampsia, which was defined as systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg and proteinuria. Controls were parturient women (N = 143) without any blood pressure values > 139/89 mm Hg or proteinuria. Obstetrical and medical characteristics were gathered from both groups through structured questionnaires. Placental histopathology examinations for malaria were performed. Twenty-eight (19.6%) vs. 16 (11.2%); P = 0.04 of the cases vs. controls, had placental malaria infections. Five (2%), 1 (2%) and 22 (28.0%) vs. 1, 2 and 13 of the placentae showed acute, chronic and past infection on histopathology examination in the two groups respectively, while 115 (80.4%) vs.127 (88.8%) of them showed no infection, P = 0.04. In multivariate analysis, while there were no associations between age, parity, educational level, lack of antenatal care, blood groups and body mass index and pre-eclampsia; family history of hypertension and placental malaria (OR = 2.3, 95% CI = 1.0-5.2; P = 0.04) were significantly associated with pre-eclampsia. Placental malaria was associated with pre-eclampsia. Further research is needed.


pH dependence of the binding of folates to milk binder in radioassay of folates.
We compare the binding of folic acid and N-5-methyltetrahydrofolic acid to milk binder in the pH range 7.4 to 10.1. At pH 7.4 the relative affinities are quite disparate, with folic acid showing the greater affinity for milk binder. As the pH is increased from 7.4 to 9.3, the difference in affinities becomes smaller, and at pH 9.3 the affinities are nearly the same. As the pH is increased from 9.3 to 10.1, the relative affinities again begin to differ, with N-5-methyltetrahydrofolic acid displaying the greater affinity. These results indicate that at a pH of 9.3 the more stable folic acid may be used as the standard in radioassay of endogenous folates.


Glycemic efficacy and safety of glucagon-like peptide-1 receptor agonist on top of sodium-glucose co-transporter-2 inhibitor treatment compared to sodium-glucose co-transporter-2 inhibitor alone: A systematic review and meta-analysis of randomized controlled trials.
Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now considered as key players in the treatment of type 2 diabetes mellitus (T2DM). The purpose of this meta-analysis was to provide precise effect estimates regarding the safety and efficacy of the addition of a GLP-1RA on top of SGLT-2i treatment. PubMed and CENTRAL, along with grey literature sources, were searched from their inception to May 2019 for randomized controlled trials (RCTs) with a duration ≥ 12 weeks, evaluating the safety and efficacy of addition of a GLP-1RA on a SGLT-2i compared to SGLT-2i alone in patients with T2DM. We also used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the credibility of our summary estimates. We identified three eligible RCTs, pooling data retrieved from 1,042 patients with T2DM in total. Administration of the maximum dose of a GLP-1RA on top of SGLT-2i treatment compared to SGLT-2i alone resulted in significant decrease in HbA1c by 0.91% (95% CI; -1.41 to -0.42) [GRADE: moderate], in body weight by 1.95 kg (95% CI; -3.83 to -0.07) [GRADE: moderate], in fasting plasma glucose by 1.53 mmol/L (95% CI; -2.17 to -0.88) [GRADE: moderate] and in systolic blood pressure levels by 3.64 mm Hg (95% CI -6.24 to -1.03). No significant effects on lipid profile and diastolic blood pressure were demonstrated. A significant increase in the risk for any hypoglycemia (RR: 2.62, 95% CI; 1.15-5.96, I2 = 33%) [GRADE: moderate] and for nausea (RR: 3.21, 95% CI; 1.36-7.54, I2 = 63%) [GRADE: moderate] and a non-significant increase in the risk for diarrhoea (RR: 1.64, 95% CI; 0.98-2.75, I2 = 0%) [GRADE: low] were documented. No other safety issues were identified. This meta-analysis suggests that a GLP-1RA/SGLT-2i combination, if tolerated, exerts significant beneficial effects on glycemic control and body weight loss, however increasing the risk for any hypoglycemia and gastrointestinal adverse events.


A new species of the genus Claassenia (Plecoptera: Perlidae) from China.
A new species, Claassenia qingzanga Xiang, Huo Du, sp. nov. is described from Tibet and Qinghai Province of western China, this is the first record of Claassenia in Qinghai-Tibet Plateau. Males of the new species are brachypterous, the apex of the aedeagus with tiny spines dorsally and with dense protrusion laterally. The new species is compared to all regional Claassenia.


Treatment of erosive osteoarthritis with peroxisome proliferator-activated receptor alpha agonist fenofibrate: a pilot study.
Hand osteoarthritis (HOA) is a common condition associated with high disease burden and frequently accompanied by comorbidities including dyslipidemia, atherosclerosis and obesity. The most debilitating HOA phenotype is erosive HOA (EHOA), characterized by synovial inflammation, formation of erosions, and substantial decline in hand function. Currently, there is no proven symptomatic treatment for the EHOA. Due to their broad spectrum effects directed on lipid metabolism, inflammation and pain, the agonists of peroxisome proliferator-activated receptor alpha or fibrates are a candidate class of drugs for the treatment of EHOA. In this study, we assessed the influence of fenofibrate treatment on clinical efficacy parameters, in vivo cytokine and adipokine production and concentrations of endothelial progenitor cells (EPC) in patients with EHOA. Fourteen patients received treatment with 145 mg of fenofibrate/day for 12 weeks. Fenofibrate treatment was associated with significant decreases in pain score, tender joint count, duration of morning stiffness, disease activity score, Cochin index, and ESR. Eight (57.14 %) patients developed Outcome Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society response at the end of treatment. Paracetamol consumption did not change during the treatment course. There was a significant reduction in triglyceride levels. No changes were detected in serum pro-inflammatory cytokine and adipokine concentrations while circulating IL-10 levels significantly decreased. There were no differences in circulating EPC numbers before and after the treatment. Fenofibrate was well tolerated, no patient experienced disease flare during the treatment. In conclusion, in EHOA patients, fenofibrate is associated with pleiotropic effects on pain, inflammation, and lipid profile. Larger, controlled studies are needed to confirm these results.