Crosslinking of DNA by busulfan. Formation of diguanyl derivatives.
High-pressure liquid chromatography has been used to separate the derivatives of guanosine which are formed when this nucleoside is reacted with busulfan. Derivatives which have been identified by a combination of ultraviolet and mass spectrometry include: 7-(delta-hydroxybutyl)guanosine, 1,4-di(7-guanosyl)butane, and 1-(7-guanyl)-4-(7-guanosinyl)butane. The latter two derivatives can be converted to 1,4-di(7-guanyl)butane by mild acid hydrolysis. Using 1,4-di(7-guanyl)butane as a marker for high-pressure liquid chromatography, we have identified this compound as a product of the reaction between DNA and busulfan. These findings verify the previously unconfirmed report that busulfan is a crosslinking agent for DNA and strengthen the hypothesis that differences in the biological properties of alkylating agents result from differences in their reactions with DNA.


Sex differences in prevalence and outcomes of the different endotypes of chronic coronary syndrome in symptomatic patients undergoing invasive coronary angiography: Insights from the global ILIAS invasive coronary physiology registry.
The management of chronic coronary syndrome (CCS) is informed by studies predominantly including men. This study investigated the relationship between patients sex and different endotypes of CCS, including sex-specific clinical outcomes. In patients with CCS undergoing coronary angiography, invasive Fractional Flow Reserve (FFR) and Coronary Flow Reserve (CFR) were measured. Patients were stratified into groups: 1) obstructive coronary artery disease (oCAD) (FFR≤0.80, no revascularization), 2) undergoing revascularization, 3) non-obstructive coronary artery disease with coronary microvascular dysfunction (CMD) (FFR>0.80, CFR≤2.5), and 4) non-obstructive coronary artery disease without CMD (FFR>0.80 and CFR>2.5). 1836 patients (2335 vessels) were included, comprising 1359 (74.0%) men and 477 (26.0%) women. oCAD was present in 14.1% and was significantly less prevalent in women than in men (10.3% vs 15.5%, respectively p < 0.01). Revascularization was present in 30.9% and was similarly prevalent in women and men (28.2% vs. 31.9%, respectively p = 0.13). CMD was present in 24.2% and was significantly more prevalent in women than men (28.6% vs 22.6%, respectively p < 0.01). Normal invasive measurements were found in 564 patients (33.0% women vs 30.0% men, p = 0.23). Male sex was associated with an increased risk of target vessel failure compared to women (HR.1.89, 95% CI 1.12-3.18, p = 0.018), regardless of CCS-endotype. Sex differences exist in the prevalence and outcomes of different endotypes of CCS in symptomatic patients undergoing invasive coronary angiography. In particular, oCAD (and subsequent revascularization) were more prevalent in men. Conversely, CMD was more prevalent in women. Overall, men experienced a worse cardiovascular outcome compared to women, independent of any specific CCS endotype.


[The influence of the continuous epidural anaesthesia on uteroplacental blood flow (author's transl)].
Continuous lumbar epidural anaesthesia causes a drop in maternal blood pressure by decreasing flow resistance in the peripheral vascular bed. By infusion of 1000 ml NaCl blood pressure can be kept constant. Our work shows, that dilatation of the peripheral vessels has a positive effect in patients with reduced uteroplacental flow, as it results in an augmentation of placental flow. In women with normal placental function such an effect could not be seen. The practical use of these results is illustraded by a case report.


Amblyomma parvitarsum (Acari: Ixodidae): localities, hosts and host-parasite ecology.
Only a few aspects of the biology of Amblyomma parvitarsum Neumann are known. Adults of this hard tick species are parasites of South American camelids in the Andean plateau of Argentina, Bolivia, Peru and Chile and also in the Argentine Patagonia, but they have been also rarely found on other artyodactils and two species of birds. The larva has been collected from reptiles in northern Chile, whereas the hosts for the nymph remain unknown. On nine localities included within Altitude Tropical and Perarid Mediterranean ecoregions in northern Chile, we analyzed 237 reptiles, 285 birds, 624 rodents and 52 camelids for infestation with A. parvitarsum to calculate seasonal prevalence of this tick. We also reviewed the literature of this tick and three entomological collections for obtaining and summarizing all the information to date about this tick. None of the analyzed birds and rodents were parasitized with A. parvitarsum; however, seven over a total of ten reptile species that we caught were infested with the larva. In the camelid species Lama glama and Vicugna pacos we collected adult specimens of this tick. Larval prevalence was higher during fall (75 %) in Liolaemus pleopholis in the Altitude Tropical ecoregion. We also collected adult specimens of A. parvitarsum from camelid manure heaps during summer in Salar de Surire and Llullaillaco localities. Additionally, we also reviewed the literature of this tick and examined specimens in three entomological collections for obtaining and summarizing all the information to date about this tick. By this study, nine localities and seven new hosts are added for A. parvitarsum and we confirm reptiles as specific hosts of this tick larva.


A comparison of distances flown by different visitors to flowers of the same species.
The morphologically complex flowers of Delphinium nelsonii, D. barbeyi, and Ipomopsis aggregata are visited by a wide variety of animals. Visitors to each species range from small insects, such as worker bumblebees and solitary bees, to hummingbirds, and thus span roughly an order of magnitude in body mass and metabolic rate while flying; they also differ in type of food collected and in their efficacy as pollinators. Despite these differences, all the visitors to a given plant species fly similar, short distances between successively visited flowers and plants. There are no significant relationships between mean flight distance and metabolic rate or body mass among the visitors to any plant species. Thus there is no evidence that flight characteristics depend on anything as straightforward as whether flower visitors have high or low energetic requirements.


Prison and the brain.
Imprisonment is a common punishment in most countries. Goals of imprisonment are often not only retribution, but also prevention. Specific prevention aims to reduce the risk of reoffending of the imprisoned offender. The question is whether the goals of retribution and specific prevention contradict each other. Retribution is not only expressed in taking away ones freedom, but also in the prison environment itself. Prisoners live in a sober regime, with a minimal amount of autonomy. There are few cognitive challenges, meaningful social interaction is reduced significantly, and many prisoners are highly sedentary. In other words, prison can be viewed as an impoverished environment. In the last few decades, much knowledge has been gained on the influence of enriched versus impoverished environment on the brain. In this chapter, we discuss the influence of the impoverished prison environment on brain functions of prisoners, with an emphasis on self-regulation and executive functions, since these functions are (1) often impaired in offenders, (2) highly sensitive to environmental influences, and (3) crucial for successful resocialization. We conclude this chapter by discussing possibilities for and potential effects of enriching prison environments.


Endopeptidase-24.15 is the primary enzyme that degrades luteinizing hormone releasing hormone both in vitro and in vivo.
The concentration of luteinizing hormone releasing hormone (LHRH) (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2), which reaches the anterior pituitary via the hypothalamo-hypophyseal portal system, appears to be controlled in part by the rate of LHRH degradation within the hypothalamus and/or pituitary. Specific, active site-directed endopeptidase inhibitors synthesized in our laboratory were used to identify the enzyme(s) involved in LHRH degradation by hypothalamic and pituitary membrane preparations, and by an intact anterior pituitary tumor cell line (AtT20). Incubation of LHRH with pituitary and hypothalamic membrane preparations led to the formation of pGlu-His-Trp (LHRH1-3) as the main reaction product. Under the same conditions, addition to the incubation mixtures of captopril, an inhibitor of the angiotensin converting enzyme, led to accumulation of pGlu-His-Trp-Ser-Tyr (LHRH1-5) and, to a lesser extent, pGlu-His-Trp-Ser-Tyr (LHRH1-6). The degradation of LHRH and the formation of the N-terminal tri- and pentapeptides was blocked by N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB), a specific, active site directed inhibitor of endopeptidase-24.15. Some inhibition of LHRH degradation and formation of the N-terminal hexapeptide was also obtained in the presence of N-[1-carboxy-2-phenylethyl]-Phe-p-aminobenzoate (cFE-F-pAB), an inhibitor of endopeptidase-24.11. Similar results were obtained with AtT20 cell membranes and with intact AtT20 cells in monolayer culture. Following cleavage by endopeptidases the C-terminal part of LHRH was rapidly degraded by aminopeptidases. Superactive analogs of LHRH in which Gly6 was replaced by a D-amino acid are resistant to degradation by both endopeptidase-24.11 and -24.15. In vivo, when LHRH was injected directly into the third ventricle of rats, the presence of cFP-AAF-pAB inhibited LHRH degradation. It is concluded that LHRH degradation is primarily initiated by the membrane-bound form of endopeptidase-24.15 to yield pGlu-His-Trp-Ser-Tyr and to a lesser extent by endopeptidase-24.11 to yield pGlu-His-Trp-Ser-Tyr-Gly.


A new indole derivative from the red alga Chondria atropurpurea. Isolation, structure determination, and anthelmintic activity.
Chondriamide C (3), a new bis(indole) amide, was isolated from the red alga Chondria atropurpurea, and its structure was established from spectroscopic data and chemical transformations. A new natural product, 3-indoleacrylamide (4), and the previously described chondriamides A and B (1, 2) and 3-indoleacrylic acid (5) were also isolated. The anthelmintic activities of compounds 1, 3, 4, and 6 (the O,N1,N1'-trimethyl derivative of compound 2) against Nippostrongylus brasiliensis in vitro were evaluated.


Lysergic acid amide-induced posterior reversible encephalopathy syndrome with status epilepticus.
Posterior reversible encephalopathy syndrome (PRES) is known to occur in association with several substances. However, lysergic acid amide (LSA) is not among the previously reported causes of PRES. We report on a patient with PRES presenting as convulsive status epilepticus associated with hypertensive encephalopathy after LSA ingestion. Magnetic resonance imaging was performed and catecholamine metabolites assayed. The patient achieved a full recovery after aggressive antihypertensive therapy and intravenous anticonvulsivant therapy. The clinical history, blood and urinary catecholamine levels, and response to treatment strongly suggest that PRES was induced by LSA. LSA, a hallucinogenic agent chiefly used for recreational purposes, should be added to the list of causes of PRES.


Tracking movement in cell biology.
This article is an overview of techniques for measuring movement of proteins, vesicles and cells using digital image processing. Diverse techniques have been developed during the last decade. Both strong and weak points of each technique are discussed, together with short description on the actual application. Among these techniques, the optical flow estimation technique is explained in more detail and an example of protein movement analysis is described.


PET/CT imaging of giant primary pulmonary meningioma: a case report and literature review.
An ectopic meningioma, such as a primary pulmonary meningioma (PPM), is a rare type of tumor that primarily originates outside of the central nervous system. The most common presentation of PPM is isolated pulmonary nodules or masses, and most of them are benign. Only sporadic cases have been reported. This case reported a giant primary pulmonary meningioma and systematically reviewed previously reported cases in the literature. A 55-year-old female suffered from asthma after activity, chest tightness, and a persistent dry cough for 2 months. Chest computed tomography (CT) showed a huge mass with calcification in the left lower lobe. And positron emission tomography (PET)/CT revealed mild FDG accumulation of the mass. The mass was finally surgically removed and PPM was confirmed according to histopathologic examinations. PPM is a rare disease with heterogeneity not only in CT features but also in glucose metabolism. FDG uptake levels do not identify benign from malignant, benign PPM may have high FDG uptake and malignant may have low.


[The influence of chosen hormones on lipids and its correlation during normal pregnancy].
Lipids and hormones levels in nonpregnant and pregnant with uneventful gestation (from I, II, III trimester) were estimated and its correlation was evaluated. The study group consisted of 219 women: 49 nonpregnant and 170 pregnant women (35 in I trimester, 35 in II and 100 in III trimester of gestation). All subjects were healthy. Following parameters were measured in blood serum: total lipids, LDL total fraction, (beta-lipoproteids), cholesterol both total and free, HDL cholesterol, LDL cholesterol. Percentage of free cholesterol contained on total cholesterol was evaluated. HPL and estrogens levels were estimated. Serum levels of total lipids, phosphlipids, triglicerides, total fraction of LDL and its contains of cholesterol increase with gestational age (p < 0.001). During pregnancy positive correlation between estrogens, HPL and triglycerides was also observed (p < 0.001). Additionally in II trimester positive correlation of total cholesterol, phospholipids and HPL was noted (respectively r = 0.469 p < 0.001 and r = 0.452 p < 0.01). In case of women with uneventful pregnancy positive correlation between estrogens and total lipids, total fractions LDL and triglycerides was stated. Also positive correlation among lipids parameters and HPL concentration was noted. No correlation between HPL and free cholesterol, LDL, HDL cholesterol nor between estrogens and total cholesterol, free cholesterol and LDL cholesterol was found. Lipids status in case of nonpregnant women is multihormonaly influenced.


Electrochemical properties of columns in capillary electrochromatography. I. Ohm's law, resistivity and field strength.
The most commonly used type of column in capillary electrochromatography (CEC) consists of a packed segment and an open (but buffer-filled) segment. The two segments differ importantly in two respects: firstly, their electrical resistivity; and secondly, their zeta potentials at a multitude of solid-liquid interfaces. Determination of the magnitude of these properties for each segment cannot be made using only results from the column as a whole. Instead, measurements of resistivity and zeta potentials of an entirely open, unpacked column can be used in conjunction with those of the CEC column to determine the electrochemical nature of both segments. This review of basic electrochemical properties will describe simple procedures that can be used to determine resistance, resistivity, conductivity, conductance, and field strength in each segment. In addition, it will be shown how the properties of each segment add together to give the same properties of the CEC column as a whole. The equations so derived will be applied to data from the literature and conclusions drawn from the results.


Impact and cost-effectiveness of family Fitness Zones: a natural experiment in urban public parks.
We evaluated the impact of outdoor exercise equipment (FZ, Fitness Zones) in 12 parks serving diverse populations. We used the System for Observing Play and Recreation in Communities (SOPARC) to assess use and estimate energy expenditure prior to and twice after FZ installation. Park use increased more in FZ parks than in 10 control parks that did not get equipment, but the difference was not statistically significant. However, self-reports of being a new park user increased more in FZ parks, and estimated energy expenditure in FZ parks was higher at both follow-ups than at baseline. Installing Fitness Zones appears to be cost-effective (10.5 cents/MET increase) and most successful in parks in densely populated areas with limited facilities. Longer-term follow-up measures are needed to determine if the early increases in physical activity associated with the Fitness Zone installations are sustained.


The cost of reproduction in a freshwater copepod.
An experimental study of the copepod Mesocyclops edax documented that females which reproduced throughout their lifetime survived at a lower rate than unmated females which did not reproduce. This cost of reproduction was most apparent in animals receiving periodic, non-lethal temperature stress. However, among reproductive females, no significant correlations were detected between reproductive output and survival, suggesting caution concerning the application of cost of reproduction arguments to a population of females in which clutch size is seen to vary.


TGF-β1 pathway affects the protein expression of many signaling pathways, markers of liver cancer stem cells, cytokeratins, and TERT in liver cancer HepG2 cells.
Liver cancer is one of the most common human malignancies, and transforming growth factor-beta (TGF-β) pathway plays a key role in its pathogenesis. To study the relationship between TGF-β pathway and the related protein expression of many signaling pathway, markers of stem cells, CK family, and others, liver cancer HepG2 cells were transfected with siRNA directed against TGF-β1 or were treated with exogenous TGF-β1. Then, these protein levels were measured by Western blotting. After siRNA transfection, TGF-β1 protein level was decreased, indicating that the siRNA against it was effective. In exogenous TGF-β1 group, the expression of smad4, smad2/3, and β-catenin proteins was increased, whereas that of p-smad2/3, CD133, cleaved Notch1, and epithelial cell adhesion molecule (EpCAM) proteins at 48 h was decreased. The expression of CK8 and CK18 proteins was increased at 24 h and was decreased at 48 and 96 h. In TGF-β1-silenced group, the expression of smad2/3, β-catenin, cleaved-notch1, and CK18 proteins was decreased, while that of smad4, p-smad2/3, CD133, EpCAM, and CK8 proteins was increased. TERT protein expression was slightly increased in exogenous TGF-β1 group at 48 h and in TGF-β1-silenced group at 96 h. TGF-β1 did not affect the protein expression of CK19 and HIF-1. Thus, TGF-β1 pathway plays an important role in cell regulation of liver cancer through the modulation of these proteins. These data will contribute to the understanding of the pathogenesis of liver cancer and the role of TGF-β pathway in this process.


Insights into palladium nanoparticles produced by Shewanella oneidensis MR-1: Roles of NADH dehydrogenases and hydrogenases.
Biologically synthesized palladium nanoparticles (bio-Pd) have attracted considerable interest as promising green catalysts for environmental remediation. However, the mechanisms by which microorganisms produce bio-Pd remain unclear. In the present study, we investigated the roles of Shewanella oneidensis MR-1 and its NADH dehydrogenases and hydrogenases (HydA and HyaB) in bio-Pd production using formate as the electron donor. The roles of NADH dehydrogenases and hydrogenases were studied by inhibiting NADH dehydrogenases and using hydrogenase mutants (ΔhydA, ΔhyaB, and ΔhydAΔhyaB), respectively. The results showed ~97% reduction of palladium by S. oneidensis MR-1 after 24 h using 250 μM palladium and 500 μM formate. Electron microscopy images showed the presence of bio-Pd on both the outer and cytoplasmic membranes of S. oneidensis MR-1. However, the inhibition of NADH dehydrogenases in S. oneidensis MR-1 resulted in only ~61% reduction of palladium after 24 h, and bio-Pd were not found on the outer membrane. The mutants lacking one or two hydrogenases removed 91-96% of palladium ions after 24 h and showed more cytoplasmic bio-Pd but less periplasmic bio-Pd. To the best of our knowledge, this is the first study to demonstrate the role of NADH dehydrogenases of S. oneidensis MR-1 in the formation of bio-Pd on the outer membrane. It also demonstrates that the hydrogenases (especially HyaB) of S. oneidensis MR-1 contribute to the formation of bio-Pd in the periplasmic space. This study provides mechanistic insights into the production of biogenic metal nanoparticles towards their possible use in industrial and environmental applications.


Optimization, validation, and application of a real-time PCR protocol for quantification of viable bacterial cells in municipal sewage sludge and biosolids using reporter genes and Escherichia coli.
Biosolids result from treatment of sewage sludge to meet jurisdictional standards, including pathogen reduction. Once government regulations are met, materials can be applied to agricultural lands. Culture-based methods are used to enumerate pathogen indicator microorganisms but may underestimate cell densities, which is partly due to bacteria existing in a viable but non-culturable physiological state. Viable indicators can also be quantified by realtime polymerase chain reaction (qPCR) used with propidium monoazide (PMA), a dye that inhibits amplification of DNA found extracellularly or in dead cells. The objectives of this study were to test an optimized PMA-qPCR method for viable pathogen detection in wastewater solids and to validate it by comparing results to data obtained by conventional plating. Reporter genes from genetically marked Pseudomonas sp. UG14Lr and Agrobacterium tumefaciens 542 cells were spiked into samples of primary sludge, and anaerobically digested and Lystek-treated biosolids as cell-free DNA, dead cells, viable cells, and mixtures of live and dead cells, followed by DNA extraction with and without PMA, and qPCR. The protocol was then used for Escherichia coli quantification in the three matrices, and results compared to plate counts. PMA-qPCR selectively detected viable cells, while inhibiting signals from cell-free DNA and DNA found in membrane-compromised cells. PMA-qPCR detected 0.5-1 log unit more viable E. coli cells in both primary solids and dewatered biosolids than plate counts. No viable E. coli was found in Lystek-treated biosolids. These data suggest PMA-qPCR may more accurately estimate pathogen cell numbers than traditional culture methods.


Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression.
Intravenous ketamine is posited to rapidly reverse depression by rapidly enhancing neuroplasticity. In human patients, we quantified gray matter microstructural changes on a rapid (24-h) timescale within key regions where neuroplasticity enhancements post-ketamine have been implicated in animal models. In this study, 98 unipolar depressed adults who failed at least one antidepressant medication were randomized 2:1 to a single infusion of intravenous ketamine (0.5 mg/kg) or vehicle (saline) and completed diffusion tensor imaging (DTI) assessments at pre-infusion baseline and 24-h post-infusion. DTI mean diffusivity (DTI-MD), a putative marker of microstructural neuroplasticity in gray matter, was calculated for 7 regions of interest (left and right BA10, amygdala, and hippocampus; and ventral Anterior Cingulate Cortex) and compared to clinical response measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR). Individual differences in DTI-MD change (greater decrease from baseline to 24-h post-infusion, indicative of more neuroplasticity enhancement) were associated with larger improvements in depression scores across several regions. In the left BA10 and left amygdala, these relationships were driven primarily by the ketamine group (group * DTI-MD interaction effects: p = 0.016-0.082). In the right BA10, these associations generalized to both infusion arms (p = 0.007). In the left and right hippocampus, on the MADRS only, interaction effects were observed in the opposite direction, such that DTI-MD change was inversely associated with depression change in the ketamine arm specifically (group * DTI-MD interaction effects: p = 0.032-0.06). The acute effects of ketamine on depression may be mediated, in part, by acute changes in neuroplasticity quantifiable with DTI.


All-trans retinoic acid added to treatment of primary immune thrombocytopenia: a systematic review and meta-analysis.
All-trans retinoic acid (ATRA) application is a novel treatment approach for primary immune thrombocytopenia (ITP). This study aimed to evaluate the efficacy and safety of ATRA in the treatment of ITP. The databases of PubMed (MEDLINE), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and China National Knowledge Internet were searched on August 5, 2022, to find randomized controlled trials (RCTs) and observational studies. Five observational studies and four RCTs from China were included, and 760 Chinese patients were analyzed. In the five observational studies, the pooled overall response rate (ORR) and complete response rate (CRR) were 59.5% (95% confidence interval [CI], 52.4-66.4%) and 20.6% (95% CI, 14.3-27.6%), respectively. In the selected four RCTs, the pooled odds ratios for sustained response rate, ORR, and CRR were 3.00 (95% CI, 1.97-4.57; P < 0.01), 3.21 (95% CI, 2.15-4.78; P < 0.01), and 2.12 (95% CI, 1.17-3.86; P = 0.01), respectively. ATRA was associated with a reduction in relapse rate and salvage treatment rate (odds ratio, 0.30; 95% CI, 0.18-0.50; P < 0.01; 0.36; 95% CI, 0.23-0.56; P < 0.01, respectively). The pooled odds ratios for grade 1-2 dry skin, headache (or dizziness), and rash acneiform were 49.99 (95% CI, 16.05-155.67; P < 0.01), 1.75 (95% CI, 0.98-3.12; P = 0.06), and 0.37 (95% CI, 0.10-1.34; P = 0.13), respectively. This study suggests that ATRA may significantly improve the initial and long-term response of patients with ITP.


Targeting heterochromatin formation to transposable elements in Drosophila: potential roles of the piRNA system.
Successful heterochromatin formation is critical for genome stability in eukaryotes, both to maintain structures needed for mitosis and meiosis and to silence potentially harmful transposable elements. Conversely, inappropriate heterochromatin assembly can lead to inappropriate silencing and other deleterious effects. Hence targeting heterochromatin assembly to appropriate regions of the genome is of utmost importance. Here we focus on heterochromatin assembly in Drosophila melanogaster, the model organism in which variegation, or cell-to-cell variable gene expression resulting from heterochromatin formation, was first described. In particular, we review the potential role of transposable elements as genetic determinants of the chromatin state and examine how small RNA pathways may participate in the process of targeted heterochromatin formation.


Which central venous catheter for neonatal use?
Complications in 100 percutaneous central venous catheters used for parenteral nutrition were monitored prospectively in patients on a regional neonatal medical and surgical unit. Infants were randomly allocated to receive either a Vygon Epicutaneous catheter or Dow Corning silastic tubing. The majority of lines -63 - were removed electively when parenteral feeding was no longer required. The most common serious complication was catheter sepsis for which 11 lines were removed; all patients made a complete recovery. Minor mechanical complications were encountered with 17 catheters. There was no difference in performance or complication rate comparing the two types of catheter. Percutaneous central venous catheters provide a suitable and safe means of administration of parenteral nutrition to preterm infants over an extended period of time.


Knowing your boundaries: no effect of tool-use on body representation following a gather-and-sort task.
Internal representations of the body have received considerable attention in recent years, particularly in the context of tool-use. Results have supported the notion that these representations are plastic and tool-use engenders an extension of the internal representation of the arm. However, the limitations of the literature underlying this tool embodiment process have not been adequately considered or tested. For example, there is some evidence that tool-use effects do not extend beyond simplistic tool-use tasks. To further clarify this issue, 66 participants engaged in a period of tool-augmented reaches in a speeded gather-and-sort task. If task characteristics inherent to simplistic tasks are relevant to putative embodiment effects, it was predicted that there would be no effect of tool-use on tactile distance judgments or forearm bisections. A Bayesian analysis found considerable support for the null hypothesis in both outcome measures, suggesting that some of the evidence for tool embodiment may be based in task characteristics inherent in the narrow range of tool-use tasks used to study them, rather than a tool incorporation process. Potential sources of influence stemming from these characteristics are discussed.


Study of interaction of poly(1-vinyl-2-pyrrolidone) with a surface of highly dispersed amorphous silica.
Interaction of poly(1-vinyl-2-pyrrolidone) with the surface of highly dispersed silica and character of its thermal destruction were investigated by means of ad-desorption measurement, vibration and electron spectroscopy, and thermal gravimetric analysis with programmed heating. The correlation between the character of polymer keeping on the surface of silicon dioxide and its thermal decomposition was established.


YouTube Videos on Nutrition and Dental Caries: Content Analysis.
Dental caries is the most common health condition worldwide, and nutrition and dental caries have a strong interconnected relationship. Foods and eating behaviors can be both harmful (eg, sugar) and healthful (eg, meal spacing) for dental caries. YouTube is a popular source for the public to access information. To date, there is no information available on the nutrition and dental caries content of easily accessible YouTube videos. This study aimed to analyze the content of YouTube videos on nutrition and dental caries. In total, 6 YouTube searches were conducted using keywords related to nutrition and dental caries. The first 20 videos were selected from each search. Video content was scored (17 possible points; higher scores were associated with more topics covered) by 2 individuals based on the inclusion of information regarding various foods and eating behaviors that impact dental caries risk. For each video, information on video characteristics (ie, view count, length, number of likes, number of dislikes, and video age) was captured. Videos were divided into 2 groups by view rate (views/day); differences in scores and types of nutrition messages between groups were determined using nonparametric statistics. In total, 42 videos were included. Most videos were posted by or featured oral health professionals (24/42, 57%). The mean score was 4.9 (SD 3.4) out of 17 points. Videos with >30 views/day (high view rate; 20/42, 48% videos) had a trend toward a lower score (mean 4.0, SD 3.7) than videos with ≤30 views/day (low view rate; 22/42, 52%; mean 5.8, SD 3.0; P=.06), but this result was not statistically significant. Sugar was the most consistently mentioned topic in the videos (31/42, 74%). No other topics were mentioned in more than 50% of videos. Low-view rate videos were more likely to mention messaging on acidic foods and beverages (P=.04), water (P=.09), and frequency of sugar intake (P=.047) than high-view rate videos. Overall, the analyzed videos had low scores for nutritional and dental caries content. This study provides insights into the messaging available on nutrition and dental caries for the public and guidance on how to make improvements in this area.


Influence of photic environment on the form of the fish electroretinographic off-response.
Scotopic electroretinogram of dogfish shark (Scylliorhinus canicula) and eel (Anguilla anguilla) is characterized by a negative off-response, changing in sign under photopic condition. It increased under the effect of increased background illumination, but its amplitude never exceeded that of the b-wave. On the other hand, dark-adapted electroretinograms of two perch-like species, perch (Perca fluviatilis) and painted comber (Serranus scriba), exhibited a positive off-wave, exceeding the b-wave amplitude under bright photopic conditions.


Rabbit anti-T-lymphocyte globulin (ATG) persists with differential reactivity in patients' sera after full hematopoetic regeneration from allogeneic stem cell transplantation.
Rabbit polyclonal anti-T-lymphocyte Globulin (ATG-F®, Fresenius) is widely used for GvHD prophylaxis in allogeneic stem cell transplantation (SCT). ATG has a wide epitope spectrum and has been shown to react with all compartments of peripheral blood mononuclear cells (PBMNCs). ATG induces apoptosis in all cellular compartments. In this study we investigated the binding of ATG in sera from ten patients treated with rabbit ATG to PBMNCs and subcellular compartments after full hematopoetic regeneration on day 21 post SCT. Sera from ten patients treated with unrelated donor allogeneic SCT for hematologic malignancy were collected after full hematopoetic regeneration on day 21 post SCT and incubated with healthy donor PBMNCs. Rabbit ATG on PBMNCs was detected by staining with fluorochrome labeled anti-rabbit IgG antibody. PBMNC compartments were investigated by counterstaining with lineage markers CD4, CD8, CD14 CD20 and CD56. Positive control was the fresh ATG preparation. We found that patient's' sera retained activity towards PBMNCs in all patients, yet at reduced intensity. When cell compartments were analyzed we found a differential pattern of ATG reactivity within sera. The mean percentage of total cells reacting with serum ATG from ten patients compared to fresh ATG (100%) was 44% of CD4 positive and 58% of CD8 positive T-lymphocytes, 41% of CD56 positive NK-cells, 83% of CD20 positive B-lymphocytes and 98% of CD14 positive monocytes. However, inter-individual variations were high with a wide spread around the mean especially for T-lymphocytes. We conclude that upon PBMNC regeneration following SCT and immunosuppressive treatment with ATG subpopulations of T-lymphocytes (CD4, CD8) and NK cells (CD56) are selected that lose epitopes recognized by ATG while B-lymphocytes (CD20) and monocytes (CD14) maintain a homogeneity with respect to epitopes recognized by ATG. This may be due to loss of idiotypes reacting with subpopulations of high frequency and turnover. Further studies should investigate the subphenotype of these populations and functional effects of extremely high or low reactivity with one or more compartments in some patients on GvHD and disease outcome.


Iron absorption by CaCo 2 cells cultivated in serum-free medium as in vitro model of the human intestinal epithelial barrier.
A cell culture system consisting of confluent monolayer of human enterocyte-like CaCo 2 cells, cultivated in a serum-free nutritive medium, on microporous synthetic membranes has been used as an in vitro model of the intestinal epithelial barrier. The uptake of 55ferric citrate, as well as the transepithelial passage from the apical to the basolateral pole, have been studied. CaCo 2 cells accumulate iron in a time- and concentration-dependent process, largely specific from the apical pole. When 55ferric citrate is added at the apical pole, radioiron appears at the basal pole and the clearance rate is approximately four times higher than in the opposite direction; the amounts of 55Fe increase with the concentration in iron citrate and the duration of incubation. At least two concurrent mechanisms could be involved in iron absorption across monolayers of CaCo 2 cells. A first route would correspond to a paracellular passage of the metal from the apical to the basal pole. The second route would involve a selective intake of iron at the apical pole and could require a reduction of ferric iron, prior to the entry. Iron accumulated by the cells would, for a minor part, be stored within ferritin, whereas the major part would be excreted at the basolateral pole, either as low molecular weight material of undetermined chemical composition but from which iron is easily mobilized by apotransferrin or associated with neosynthesized apotransferrin. Vesicular transport and protein synthesis seem to be required.


Coffee silverskin as nutraceutical ingredient in yogurt: its effect on functional properties and its bioaccessibility.
Silverskin is a by-product obtained from coffee roasting. It is characterized by a high content of dietary fibre, phenolic compounds and caffeine. The aim of this study was to assess the silverskin obtained from two species of Coffea (Arabica and Robusta) at three percentages (2%, 4%, or 6%) into cow whole-milk yogurt to raise the nutraceutical value of the products and to verify the bioaccessibility of bioactive compounds during the shelf-life of 3 weeks. The amount and origin of silverskin significantly influenced all the physicochemical parameters. Concerning the bioactive compounds, the highest levels were observed in yogurt supplemented with 6% of silverskin. Between the coffee species, Arabica yielded the highest 5-caffeoylquinic acid content and the strongest antioxidant activity, whereas Robusta gave the highest caffeine content. The digestion increased antioxidant activity in the yogurt, possibly because of greater accessibility of compounds. The results obtained highlighted that silverskin can be used in yogurt production to increase the nutraceutical value of the products and that the bioactive compounds are bioaccessible during the digestion process. The characteristics and bioaccessibility of the resulting yogurt were strongly correlated with the coffee species and with the percentage added. © 2019 Society of Chemical Industry.


Dietary leucine improves whole-body insulin sensitivity independent of body fat in diet-induced obese Sprague-Dawley rats.
Dairy foods and dietary calcium (Ca) are potential regulators of body weight and insulin sensitivity. The specific components of dairy responsible for these actions are not known but may include leucine. Our objective was to determine the effect of dietary protein (casein, skim milk or leucine) and Ca level [low, 0.67% (LC) or high, 2.4% (HC)] on adiposity and insulin sensitivity. Obesity was induced in Sprague-Dawley rats with a 6-week period of high-fat/high-sucrose (HFHS) diet intake. Rats were randomly assigned to one of six HFHS diets for 8 weeks where dietary protein was provided as casein, skim milk or casein enriched with leucine, and contained either LC or HC. Body composition via dual-energy x-ray absorptiometry and insulin sensitivity via euglycemic-hyperinsulinemic clamp were measured. Microarray was used to assess gene expression in liver and skeletal muscle. Rats fed leucine had greater insulin sensitivity than those fed casein or skim milk (P<.05). Dietary protein differentially regulated hepatic and skeletal muscle genes associated with insulin, peroxisome proliferator-activated receptor and mammalian target of rapamycin pathways. Specifically, two key genes responsible for insulin sensitivity, hepatic insulin receptor substrate (IRS) and protein kinase B (Akt), were altered in hepatic tissue in response to leucine. Rats fed skim milk and leucine diets had lower body weight compared to those fed casein (P<.05). HC reduced fat mass compared to LC (P<.05). While skim milk and leucine both reduced fat mass, only leucine improved insulin sensitivity compared to casein. Differential expression of genes such as IRS and Akt may be responsible for changes in insulin sensitivity in obese rats.


Extracorporeal membrane oxygenation in immunocompromised patients with acute respiratory failure: A retrospective cohort study.
The clinical indications of extracorporeal membrane oxygenation (ECMO) in immunosuppressed patients are not clear. This study aimed to analyse the effectiveness of ECMO and to identify the risk factors for the mortality of ECMO in immunocompromised patients with acute respiratory failure. This retrospective, cohort study included 46 confirmed immunocompromised patients with acute hypoxemic respiratory failure treated with ECMO between July 2014 and August 2020. The clinical features and outcomes of the survival group and the non-survival group were statistically analysed. The mean age of the enrolled patients was 60.0 (50.0, 66.0) years; male patients accounted for 60.9% of patients, and the mean CD4 level was 213 cells/μL (150.3, 325.3). The hospital mortality rate of the cohort was 67.4% (31/46 patients). Patients in the survival group showed a higher rate of receiving awake ECMO (11/15 vs. 4/31; p = 0.006), a lower rate of acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT) (1/15 vs. 12/31; p = 0.035), fewer platelet transfusion units (0/15 vs. 2/31 units; p = 0.039) and a lower rate of ventilator-associated pneumonia (2/15 vs. 19/31; p = 0.006). In a multivariate Cox regression analysis model, intubated ECMO (hazard ratio = 1.77, 95% confidence interval: 1.34-2.32, p < 0.001) and AKI requiring CRRT (1.37, 95% confidence interval: 1.14-1.61, p = 0.003) were identified as independent risk factors for mortality. In-hospital mortality has remained high in ECMO-treated immunocompromised patients with acute respiratory failure. Intubated ECMO and AKI receiving CRRT during ECMO treatment may predict ECMO failure in immunocompromised patients with ARF. A primarily awake ECMO strategy seems feasible in some selected immunocompromised patients.


Evolution analysis of Dof transcription factor family and their expression in response to multiple abiotic stresses in Malus domestica.
As a family of transcription factors, DNA binding with one figure (Dof) proteins play important roles in various biological processes in plants. Here, a total of 60 putative apple (Malus domestica) Dof genes (MdDof) were identified and mapped to different chromosomes. Chromosomal distribution and synteny analysis indicated that the expansion of the MdDof genes came primarily from segmental and duplication events, and from whole genome duplication, which lead to more Dof members in apples than in other plants. All 60 MdDof genes were classified into thirteen groups, according to multiple sequence alignment and the phylogenetic tree constructed of Dof genes from apple, peach (Prunus persica), Arabidopsis and rice. Within each group, the members shared a similar exon/intron and motif compositions, although the sizes of the MdDof genes and encoding proteins were quite different. Several Dof genes from the apple and peach were identified to be homologues based on their close synteny relationship, which suggested that these genes bear similar functions. Half of the MdDof genes were randomly selected to determine their responses to different stresses. The majority of MdDof genes were quite sensitive to PEG, NaCl, cold and exogenous ABA treatment. Our results suggested that MdDof family members may play important roles in plant tolerance to abiotic stress.


Effects of the relative positioning between the disc-fovea angle and localized optic disc defects on the 10-2 visual field results in glaucoma.
To investigate the effects of the foveal position relative to the optic disc on the 10-2 visual field (VF) results of glaucoma patients with localized inferotemporal neuroretinal rim defects (ITD). Cross-sectional study. Fifty-seven eyes of 35 open-angle glaucoma (OAG) patients were included and divided into two groups based upon the presence (18 eyes) or not (39 eyes) of ITD. Three different parameters obtained from a spectral domain optic coherence tomography (sdOCT) [disc-fovea angle (DFA), fovea vertical deviation (FVD) from midline, and the angular difference between the ITD border and the DFA (DAD)] were tested for their relationship with four 10-2 VF sectors: superior hemifield, superior edge, nasal edge, and superonasal arcuate. These relationships were tested with regression analyses with linear mixed effects models and random intercepts. Influences of DFA, FVD, and DAD on 10-2 VF sectors. Mean (±SD) values of DFA, FVD, and DAD were respectively: -5.05° ± 4.40°, -1346.6 um ± 1609.0 um, and 43.30° ± 17.33°. After adjustment for multiple comparisons, both FVD and DAD, but not DFA, were significantly associated with the severity of defects on the predefined VF sectors. Larger DAD values (third tertile: 54°-77°) showed higher coefficient estimate for the nasal edge sector sensitivities. The vertical foveal location and its position relative to the ITD was associated with loss of sensitivity at 10-2 VF locations in the superior hemifield. This association was significant but weak and was not seen using other conventional parameters that describe foveal position relative to the optic disc on sdOCT.


Bottom-up synthesis of mesoporous germanium as anodes for lithium-ion batteries.
A series of mesoporous germanium materials were synthesized via the self-templating method. Germanium tetrachloride and sodium potassium alloy were utilized as germanium precursor and reducing agent, respectively. The by-products, NaCl and KCl, could be considered as the in-situ templates. The characterization results showed that the mesopores could be obtained, when the salts were removed by water washing. Moreover, the crystalline germanium could also be achieved, when the calcination temperature is as high as 500 °C. However, when the calcination temperatures are 300 °C, the as-received mesoporous germanium materials are amorphous. When evaluated as anode for lithium-ion batteries (LIBs), the obtained mesoporous germanium exhibits outstanding cycling stability, showing a high reversible specific capacity of 803 mA h g-1 after 100 cycles, as well as enhanced rate performance (655 mA h g-1 at 1 C rate).


Surgical Advances in the Management of the Silent Sinus Syndrome: Our Experience and Review of the Literature.
Silent sinus syndrome is a rare disorder characterized by ipsilateral enophthalmos and hypoglobus caused by collapse of the orbital floor in the presence of asymptomatic long-term maxillary sinusitis. The basic principles in the management are to address the diseased sinus and reconstruct the orbit concurrently or separately. Failure to accurately restore the orbit volume can have significant consequences on the patient. In this article, we provide an update on current practices and highlight our experience of using computer-assisted planning and patient-specific implant in managing this syndrome.


Novel application of pyronin Y fluorophore as high sensitive optical sensor of glucose in human serum.
This paper presents a novel, high sensitive, facile and rapid spectrofluorimetric method for the direct assessment of glucose in human serum samples. The strong fluorescence intensity of pyronin Y (PY) is found to be selectively quenched substantially by adding solutions of glucose. Therefore, a new quantitative method to determine glucose could be developed. The noticeable and specific quenching effect of glucose on PY emission could be attributed to the increase in the nonradiative interactions as a result of a charge-transfer excited state with the location of the positive charge at the xanthenes moiety. Various parameters namely, the best working solvent, the proper pH medium in addition to the concentration of PY fluorophore corresponding to maximum fluorescence intensity were closely investigated. Under optimal conditions, the standard curve was linear in the glucose concentration ranges from 5.0×10(-9) to 1.0×10(-6)molL(-1) (r=0.994). The detection limit (S:N=3) (LOD) is 2.9×10(-9)molL(-1). Validation of this approach was done by examining glucose concentration in serum samples of twenty patient and ten health donors. Achieved recovery reached 99.63-100.43% and 99.57-100.70%, respectively, in good agreement with those provided from hospital using traditional method. The relative standard deviations (RSD) were estimated between 0.00-0.78% and 0.15-1.91%, respectively.


Ultrasound-guided peripheral intravenous cannulation for patients requiring dental surgery under intravenous dental sedation.
Dental surgeons regularly provide intravenous dental sedation and oral/transmucosal sedation, which involves cannulation. Cannulation is an essential skill that dental surgeons should be competent to perform, but certain patient groups may be difficult to cannulate. Ultrasound-guided peripheral intravenous cannulation is an evidence-based technique already used in radiology, emergency medicine, and anaesthesia. Ultrasound-guided peripheral intravenous cannulation has been shown to reduce complications and significantly increase the success of cannulation in patients with difficult intravenous access (DIVA); it may also be preferable in certain special care patient groups. The application of ultrasound-guided peripheral intravenous cannulation should be considered for patients with DIVA who require intravenous dental sedation or other common procedures in dental surgery that involve cannulation.


Effects and regulatory pathway of proopinmelanocortin on feeding habit domestication in mandarin fish.
Proopiomelanocortin (POMC) is a hormone precursor, and has been reported to participate in domestication. However, its effects on feeding habit domestication in fish are poorly understood. Mandarin fish (Siniperca chuatsi) feeds solely on live prey fish since first-feeding. In the present study, the high expression of pomc in mandarin fish, both the pomc siRNA and MC4R inhibitor treatments increased the success rate of domestication from live prey fish to dead prey fish and food intake of dead prey fish, suggesting the role of pomc on the special feeding habit of live prey fish in mandarin fish. In addition, one c-fos binding site was identified in the region that from -1053 bp to -931 bp upstream of the transcription start site of pomc, and this region exhibited positive promoter activity. The mandarin fish brain cells treated with c-fos siRNA displayed suppressed pomc mRNA expression, indicating that c-fos positively regulated pomc expression. Furthermore, the mRNA expression of c-fos was higher in the mandarin fish which were more difficult to domesticate. The results of ChIP assay and inhibitor treatment confirmed that the activation of c-fos gene by histone H3K4me3 was catalyzed by Setd1b in mandarin fish. Three open peaks were found at the upstream regulatory region of setd1b by ATAC-seq, and the mRNA expression of setd1b was higher in the mandarin fish which were more difficult to domesticate. These results indicated that Setd1b could methylate histone H3K4 to activate the c-fos transcription, maintaining the high expression of pomc, which might contribute to the special feeding habit of mandarin fish.


Detection of non-pylori Helicobacter species in "Helicobacter heilmannii"-infected humans.
A small proportion of patients suffering from chronic active gastritis are diagnosed with gastric Helicobacter species other than Helicobacter pylori. Circumstantial evidence has suggested that these bacteria, also referred to as "Helicobacter heilmannii"-like organisms (HHLO), may be transmitted through animals. The isolation of a Helicobacter bizzozeronii strain from a human patient confirmed this hypothesis. It was the aim of the present study to assess the presence of animal Helicobacter species and H. pylori in humans infected with HHLO, as diagnosed by histology. Paraffin-embedded gastric biopsy specimens of 108 HHLO-infected patients (42 women and 66 men) from three clinical centers were screened for the presence of animal gastric Helicobacter species by polymerase chain reaction (PCR), using assays targeting the 16S rDNA region of the three known canine and feline helicobacters (H. bizzozeronii, H. salomonis and H. felis), "Candidatus H. suis", and "Candidatus H. bovis". In addition, the presence of H. pylori was evaluated by multiplex PCR analysis. In 63.4% of the stomachs (64/101) classification of the Helicobacter infection into the above mentioned groups was achieved. Non-pylori Helicobacter species commonly colonizing the stomachs of cats and dogs were found in 48.5% (49/101) of the patients. Fourteen (13.9%) samples tested positive for "Candidatus H. suis", and "Candidatus H. bovis" was demonstrated in 1 (0.9%) patient. The presence of H. pylori was established in 13 patients (12.9%). Eleven stomachs (10.9%) were infected with at least two different Helicobacter species. This study identifies animal Helicobacter species in the stomach of a large series of HHLO-infected patients, which may have clinical implications in a subset of patients with gastric disease.


Comparing Clinicopathologic and Radiographic Findings Between TT-UMP, Classical, and Non-Encapsulated Follicular Variants of Papillary Thyroid Carcinomas.
Thyroid tumors of uncertain malignant potential (TT-UMP) comprise an accepted subgroup of follicular-patterned thyroid tumors for which benignancy or malignancy cannot be precisely assessed. We aimed to evaluate the demographic characteristics, ultrasound (US) findings, and cytological results of patients with TT-UMP and compare these findings to a classical variant of papillary thyroid carcinoma (CV-PTC) and non-encapsulated follicular variant of PTC (NEFV-PTC) patients; we also evaluated the immunohistochemical characteristics of patients with TT-UMP. Twenty-four patients with TT-UMP, 672 with CV-PTC, and 132 with NEFV-PTC were included in the study. Mean longitudinal nodule size and median nodule volume were higher in the TT-UMP group than in the CV-PTC and NEFV-PTC groups (p < 0.001 and p < 0.001 for CV-PTC; p < 0.001 and p = 0.008 for NEFV-PTC). The presence of halo and peripheral vascularization was observed more frequently in the TT-UMP group than in the CV-PTC group (p = 0.002 and p = 0.024). Benign and follicular neoplasm/suspicious for follicular neoplasm cytological results were higher in the TT-UMP group than in the CV-PTC group (p = 0.030 and p = 0.001). US findings were similar between TT-UMP and NEFV-PTC groups (all, p > 0.05). However, none of the patients with TT-UMP were called malignant; 105 patients (31.2 %) of CV-PTC and 11 patients (9.5 %) of NEFV-PTC (infiltrative FV) were classified as malignant cytologically. Tumor size was higher in the TT-UMP group than in the CV-PTC and NEFV-PTC groups (p < 0.001 and p = 0.006). In the TT-UMP group, positive expression of HBME-1, CK-19, and Gal-3 was found in 50, 33.3, and 25 % of patients, respectively. This study demonstrated that none of the TT-UMP patients were evaluated as malignant in preoperative cytology. However, patients with TT-UMP had higher nodule and tumor sizes than CV-PTC and NEFV-PTC patients; US features were similar between NEFV-PTC and TT-UMP patients.


Fetal development in alloxan-treated rats.
The effect of alloxan on embryo and fetal development in rats was evaluated. Alloxan was injected intraperitoneally (ip) in pregnant rats at doses of 80 to 150 mg/kg at Day 0 (day of fertilization), and 110 mg/kg at Day 4 of pregnancy. Hyperglycemia was rarely produced at alloxan doses from 80 to 100 mg/kg, and the frequency of malformations observed was low. Higher doses (110 to 150 mg/kg) caused severe hyperglycemia, and maternal or embryonic death. When 110 mg/kg was administered on Day 4 of gestation (the day before embryo implantation), all rats had resorption nodules and litters with embryos with delayed growth. We recommend the induction of diabetes mellitus on Day 4 of pregnancy for studies of diabetes-gestation interaction.


Rapid isolation and identification of reovirus-3.
Mammalian reoviruses are connected with a variety of humans diseases, including gastroenteritis, malabsorption and hepatitis. Recently, reovirus-3 was found to be associated with neonatal biliary atresia. We describe a technique for the rapid isolation and identification of reovirus-3. Mouse fibroblasts (L 929 cells) were grown in monolayers in a RPMI 1640 medium containing 10% calf serum. The cytopathic effects were visualized by the rounding of the L 929 cells and the appearance of fine granulation in the cytoplasm 48 h after the infection. Hematoxylin-eosin staining showed swelling and rounding of the infected cells, diminished chromatin in the nuclei, and the absence of mitoses. The immunohistochemical staining by the avidin-biotin-peroxidase technique was positive in the infected monolayers of the L 929 cells. The positive staining was limited to cytoplasmic inclusions, which were surrounded by a halo and sometimes by vacuoles. We conclude that the described technique is useful for the rapid isolation and identification of reovirus-3.


Therapeutic applications of gene editing in chronic liver diseases: an update.
Innovative genome editing techniques developed in recent decades have revolutionized the biomedical research field. Liver is the most favored target organ for genome editing owing to its ability to regenerate. The regenerative capacity of the liver enables ex vivo gene editing in which the mutated gene in hepatocytes isolated from the animal model of genetic disease is repaired. The edited hepatocytes are injected back into the animal to mitigate the disease. Furthermore, the liver is considered as the easiest target organ for gene editing as it absorbs almost all foreign molecules. The mRNA vaccines, which have been developed to manage the COVID-19 pandemic, have provided a novel gene editing strategy using Cas mRNA. A single injection of gene editing components with Cas mRNA is reported to be efficient in the treatment of patients with genetic liver diseases. In this review, we first discuss previously reported gene editing tools and cases managed using them, as well as liver diseases caused by genetic mutations. Next, we summarize the recent successes of ex vivo and in vivo gene editing approaches in ameliorating liver diseases in animals and humans. [BMB Reports 2022; 55(6): 251-258].


The role of Rhipicephalus sanguineus ticks parasitizing dogs in the spread of tick-borne rickettsial pathogens in the city of Sevastopol.
The occurrence of Mediterranean fever with periods of increase and decrease has been recorded in the Crimean peninsula. The city of Sevastopol and its vicinity are known endemic areas for this disease. Some of the most active agents in the spread of this rickettsiosis are feral and abandoned dogs. The aim of this study was to test ticks parasitizing dogs in Sevastopol for the presence of Rickettsia using molecular methods. The testing of ticks was carried out using real-time PCR and the 'Real Best DNA Rickettsia species' kit (AO 'Vector-Best') followed by sequence identification of the rickettsial DNA detected. The DNA marker for Rickettsia species (a conservative area of citrate synthase gene, gltA) was detected in 16 of 84 (19.1%) samples of Rhipicephalus sanguineus ticks tested. Larger fragments of gltA, ompA and sca4 were amplified and sequenced for 10 of 16 PCR-positive samples. Rickettsia DNA amplified from eight of the samples matched the sequence of Rickettsia conorii conorii Malish, the causative agent of Mediterranean fever. The sequences of Rickettsia DNA from two other ticks had the closest match to homologous fragments of Rickettsia massiliae, a pathogenic spotted fever rickettsia that was identified in the Crimean Peninsula for the first time as part of this study. The detection of two pathogenic species of Rickettsia in the studied ticks suggests the potential for two rickettsial diseases in the region and warrants further epidemiological and clinical studies.


Is there a bilingual advantage on interference-control tasks? A multiverse meta-analysis of global reaction time and interference cost.
A contentious issue in contemporary psycholinguistics is whether bilingualism enhances executive functions. Here, we report a meta-analysis of 80 studies (253 effect sizes) comparing performance of monolinguals and bilinguals on non-verbal interference-control tasks, while examining potential moderators of effects on two dependent variables (DVs): global reaction time (RT) and interference cost. We used a multiverse approach to determine how robust conclusions were to several dataset construction and analysis decisions. In our "preferred" analysis, using a broad definition of bilinguals and standard versions of interference-control tasks, there was a very small but significant bilingual advantage for global RT (g =.13), which became non-significant once corrected for publication bias. For interference cost, there was a very small but significant bilingual advantage (g =.11). Effects were not significantly moderated by task or participant age, but were moderated by an interaction between age of second language acquisition (AoA) and the DV. Unexpectedly, larger effect sizes for interference cost were observed for studies involving bilinguals with late as opposed to early AoA. The multiverse analysis produced results largely consistent with the preferred analysis, confirming our conclusion that evidence for a bilingual advantage on interference-control tasks is weak.


Fluorimetric determination of cerium(IV) with ascorbic acid.
A simple, sensitive, and selective method for the determination of cerium(IV), based on the oxidative reaction between cerium(IV) and ascorbic acid, has been described. The fluorescence comes from Ce(III) at lambda(excitation) 298 nm and lambda(emission) 358 nm, which, in turn, is obtained from the oxidation of ascorbic acid by Ce(IV) in the presence of sulfuric acid. The optimum conditions such as concentrations of ascorbic acid, sulfuric acid media and pH of the buffer solution were investigated. The fluorescent intensity of the system is linear over the range 0.0531 microg/ml to 0.3322 mg/ml Ce(IV) and detection limit and correlation coefficient are 0.0145 microg/ml and R=0.99987, respectively.


Utilization of freshwater mussel (Lamellidens marginalis) for the isolation of proteins through pH shift processing: characterization of isolates.
Study was conducted to use underutilized freshwater mussel (Lamellidens marginalis) for the recovery of proteins using pH shift method and to study the functionality and characteristics of the recovered isolates. From the pH range tested (pH 2.0-13.0), maximum protein yields were obtained during solubilization at pH 2.0 and pH 13.0 (p < 0.05). During the protein recovery process, pH 13.0 was found to have minimal effect on proteins resulting in higher protein yields compared to pH 2.0. Isolates obtained by both acidic and alkaline solubilization processes had low stability and poor gel network. Total lipid content, total myoglobin, and pigment contents were reduced significantly (p < 0.05) during pH shift processing, resulting in whiter protein isolates and protein gels. All the essential amino acids were present in the isolates recovered by acid and alkaline solubilization, indicating the complete recovery of amino acids. No microbial counts were observed in any of the isolates prepared using acid and alkaline-aided processing. Acid and alkaline solubilization (pH shift) process was found to be promising for the recovery of proteins from underutilized freshwater mussel thus by reducing the supply demand gap.


Cost-effectiveness of custom-made insoles versus usual care in patients with plantar heel pain in primary care: cost-effectiveness analysis of a randomised controlled trial.
To evaluate the cost-effectiveness of custom-made insoles compared with general practitioner (GP)-led usual care after 26 weeks of follow-up in individuals with plantar heel pain (PHP) from a societal perspective. Cost-effectiveness analysis of a double-blinded randomised controlled trial. General practice in the Netherlands. 116 participants with PHP for at least 2 weeks, aged 18-65 years and presenting to the GP. Participants were randomised to GP-led usual care (n=46) or referral to a podiatrist for treatment with a custom-made insole (n=70). Participant randomised to a sham insole (n=69) were excluded from this analysis. Outcomes comprised pain during rest and activity, and quality of life. Costs included healthcare and lost productivity costs. Statistical uncertainty was estimated using bootstrapping and presented using cost-effectiveness acceptability curves. Participants in the custom-made insole group experienced statistically significant more pain during activity at 26 weeks than participants in the usual care group (overall effect 1.06; 95% CI 0.36 to 1.75). There were no significant differences between groups in other outcomes. Total societal costs in the custom-made insole group were non-significantly higher than in the usual care group (mean difference €376; 95% CI -€1775 to €2038). The intervention with custom-made insoles was dominated by usual care by the GP (ie, more expensive and less effective) for pain during activity and quality of life outcomes. For the outcome pain at rest, the intervention was more expensive and more effective than usual care. However, the maximum probability of cost-effectiveness was only 0.59 at very high ceiling ratios. These findings show that that custom-made insoles are not cost-effective in comparison with GP-led usual care. Clinicians should be reserved in prescribing custom-made insoles for PHP as a primary intervention. NTR5346.


Development of a remineralizing calcium phosphate nanoparticle-containing self-etching system for orthodontic bonding.
This study aimed to incorporate hydroxyapatite nanoparticles (nHA) or amorphous calcium phosphate nanoparticles (nACP) into a self-etch primer (SEP) to develop a simplified orthodontic bonding system with remineralizing and enamel preserving properties. nHA and nACP were incorporated into a commercial SEP (Transbond™ plus) in 7% weight ratio and compared with the plain SEP as a control. Shear bond strengths (SBS), enamel damage, and adhesive remnant index (ARI) scores were evaluated at 24 h and post 5000 thermocycling. Field-emission scanning electron microscope (FESEM) was used to inspect the distribution of the nanoparticles in the experimental SEPs and evaluate the enamel surface integrity both before bracket bonding and post bracket debonding. Phase determination and remineralizing capability of the modified SEP were characterized by X-ray diffraction and Raman spectroscopy, respectively. The addition of nHA or nACP to the SEP significantly reduced the SBS, ARI, and enamel damage (p < 0.05) as compared to the control SEP; however, only nHA-SEP survived the thermocycling protocol and yielded acceptable SBS (13.38 MPa). Enamel remineralizing ability of the developed nHA-SEP was confirmed by both FESEM images and Raman phosphate map. Incorporating nHA into SEP resulted in clinically acceptable bond strengths with remineralizing ability. The newly developed nHA-SEP has unprecedented ability to simultaneously etch, prime, and remineralize the enamel in a single step leaving immaculate enamel surface with the potential of saving cost and time at the post-debonding step.


Effect of concomitant use of pitavastatin with neoadjuvant chemotherapy protocols in breast cancer patients: A randomized controlled clinical trial.
Preclinical studies have demonstrated the possible anticancer effects of statins, but the synergistic effect of concomitant statin use with standard chemotherapy protocols in patients with breast cancer has not yet been investigated. The current study aimed to evaluate the efficacy of concomitant pitavastatin use with neoadjuvant chemotherapy protocols in patients with breast cancer. This study was a randomized controlled clinical trial. A total of 70 adult female patients with pathologically-proven invasive breast cancer were randomized to receive or not receive pitavastatin (2 mg) oral tablets once daily concomitantly with standard neoadjuvant chemotherapy protocols for 6 months. The primary outcomes of this study were changes in tumor size and changes to the Ki67 index. In addition, secondary outcomes were changes in cyclin D1 and cleaved caspase-3 serum levels. This study was registered at ClinicalTrials.gov (Identifier: NCT04705909). Patients in the pitavastatin group showed significantly higher median (IQR) reductions in tumor size [-19.8 (-41.5, 9.5)] compared to those in the control group [-5.0 (-15.5, 0.0), p = 0.0009]. The change in Ki67 from baseline to the end of therapy was similar between the two groups (p = 0.12). By the end of therapy, the cyclin D1 levels in the pitavastatin group were significantly decreased [median (IQR) change of - 10.0 (-20.2, -2.9) from baseline], whereas the control group showed an increase in cyclin D1 levels [14.8 (4.1, 56.4)]. The median (IQR) caspase-3 was elevated in the pitavastatin group 1.6 (0.2, 2.2), and decreased in the control group (-0.2 (-1.1, 0.0), p = 0.0002).Subgroup analysis of the pitavastatin group revealed that patients with positive human epidermal growth receptor 2 (HER2) had higher median (IQR) reductions in Ki67 [-35.0 (-70.0, -12.5)] than those with negative HER2 [2.5 (-15.0, 10.0), p = 0.04]. All patients who achieved a complete pathological response (n = 9) exhibited an HER2-neu positive receptor at baseline. Concomitant use of pitavastatin with standard neoadjuvant chemotherapy protocols may improve neoadjuvant chemotherapy responses in patients with breast cancer.


Cases of mercury exposure, bioavailability, and absorption.
Mercury is a unique element that, unlike many metals, has no essential biological function. It is liquid at room temperature and is 13.6 times heavier than water. Its unique physical properties have been exploited for a variety of uses such as in mercury switches, thermostats, thermometers, and other instruments. Its ability to amalgamate with gold and silver are used in mining these precious metals and as a dental restorative. Its toxic properties have been exploited for medications, preservatives, antiseptics, and pesticides. For these reasons there have been many industrial uses of mercury, and occupational exposures of workers and industrial emissions and effluents contaminating air, water, soil, and ultimately food chains have long been a matter of great public health concern. This paper examines briefly six cases representing various forms of exposure to different species of mercury, and indicates the methodological issues in estimating exposure, bioavailability and absorption; these cases include Minamata disease in Japan, organic mercury poisoning in Iraq, methylmercury (MeHg) exposure in the Amazon, dimethylmercury (PMM) in the laboratory, an elemental mercury spill in Cajamarca, Peru, and a mercury-contaminated building in Hoboken, NJ, USA. Other scenarios that are not described include occupational exposure to mercury salts, mercurial preservatives in vaccines, cultural and ritualistic uses of mercury, and mercury in dental amalgams.


Effect of apolipoprotein E-free high density lipoproteins on cholesterol metabolism in cultured pig hepatocytes.
We studied cholesterol synthesis from [14C]acetate, cholesterol esterification from [14C]oleate, and cellular cholesterol and cholesteryl ester levels after incubating cells with apoE-free high density lipoproteins (HDL) or low density lipoproteins (LDL). LDL suppressed synthesis by up to 60%, stimulated esterification by up to 280%, and increased cell cholesteryl ester content about 4-fold. Esterification increased within 2 h, but synthesis was not suppressed until after 6 h. ApoE-free HDL suppressed esterification by about 50% within 2 h. Cholesterol synthesis was changed very little within 6 h, unless esterification was maximally suppressed; synthesis was then stimulated about 4-fold. HDL lowered cellular unesterified cholesterol by 13-20% within 2 h and promoted the removal of newly synthesized cholesterol and cholesteryl esters. These changes were transient; by 24 h, both esterification and cellular unesterified cholesterol returned to control levels, and cholesteryl esters increased 2-3-fold. HDL core lipid was taken up selectively from 125I-labeled [3H]cholesteryl ester- and ether-labeled HDL. LDL core lipid uptake was proportional to LDL apoprotein uptake. The findings suggest that 1) the cells respond initially to HDL or LDL with changes in esterification, and 2) HDL mediates both the removal of free cholesterol from the cell and the delivery of HDL cholesteryl esters to the cell.


High-risk CT features for detection of local recurrence after stereotactic ablative radiotherapy for lung cancer.
Early detection of local recurrences following stereotactic ablative radiotherapy (SABR) for lung cancer may allow for curative salvage treatment, but recurrence can be difficult to distinguish from fibrosis. We studied the clinical performance of CT imaging high-risk features (HRFs) for detecting local recurrence. Patients treated with SABR for early stage lung cancer between 2003 and 2012 who developed pathology-proven local recurrence (n=12) were matched 1:2 to patients without recurrences (n=24), based on baseline factors. Serial CT images were assessed by blinded radiation oncologists. Previously reported HRFs were (1) enlarging opacity at primary site; (2) sequential enlarging opacity; (3) enlarging opacity after 12-months; (4) bulging margin; (5) loss of linear margin and (6) air bronchogram loss. All HRFs were significantly associated with local recurrence (p<0.01), and one new HRF was identified: cranio-caudal growth (p<0.001). The best individual predictor of local recurrence was opacity enlargement after 12-months (100% sensitivity, 83% specificity, p<0.001). The odds of recurrence increased 4-fold for each additional HRF detected. The presence of ≥3 HRFs was highly sensitive and specific for recurrence (both >90%). The systematic assessment of post-SABR CT images for HRFs enables the accurate prediction of local recurrence.


Triple-Stranded DNA As a Structural Element in DNA Origami.
Molecular self-assembly with DNA origami offers an attractive route to fabricate arbitrary three-dimensional nanostructures. In DNA origami, B-form double-helical DNA domains (dsDNA) are commonly linked with covalent phosphodiester strand crossovers to build up three-dimensional objects. To expand the palette of structural motifs in DNA origami, here we describe hybrid duplex-triplex DNA motifs as pH-dependent building blocks in DNA origami. We investigate design rules for incorporating triplex forming oligonucleotides and noncanonical duplex-triplex crossovers in multilayer DNA origami objects. We use single-particle cryoelectron microscopy to elucidate the structural basis of triplex domains and of duplex-triplex crossovers. We find that duplex-triplex crossovers can complement and fully replace the canonical duplex-duplex crossovers within DNA origami objects, for example, to increase the crossover density for potentially greater rigidity and reduced interhelical spacing, and to create connections at sites where conventional crossovers may be undesirable. We also show the pH-induced formation of a DNA origami object stabilized entirely by triplex-mediated strand crossovers.


Sympathetic tales: subdivisons of the autonomic nervous system and the impact of developmental studies.
Remarkable progress in a range of biomedical disciplines has promoted the understanding of the cellular components of the autonomic nervous system and their differentiation during development to a critical level. Characterization of the gene expression fingerprints of individual neurons and identification of the key regulators of autonomic neuron differentiation enables us to comprehend the development of different sets of autonomic neurons. Their individual functional properties emerge as a consequence of differential gene expression initiated by the action of specific developmental regulators. In this review, we delineate the anatomical and physiological observations that led to the subdivision into sympathetic and parasympathetic domains and analyze how the recent molecular insights melt into and challenge the classical description of the autonomic nervous system.


Understanding redundancy and resilience: Redundancy in life is provided by distributing functions across networks rather than back-up systems: Redundancy in life is provided by distributing functions across networks rather than back-up systems.
Understanding how evolution generates and maintains redundancy to cope with damage and loss of function in living systems could inspire applications from new therapies to resilient computer networks.


Analysis of adenoid cystic carcinoma treated by radiotherapy.
The records of 41 patients with adenoid cystic carcinoma of the head and neck region who had been treated with radiotherapy were reviewed. Local control was achieved in 72.3% in the cases with primary lesions at 5 years. The prognosis for tumors that arose in the major salivary glands was better than that for tumors that arose in the minor salivary glands; however, the difference was not statistically significant. In the minor salivary glands, early-stage tumors were well controlled with the use of radiation therapy alone. In spite of the high local control rate, the disease-free survival rate of the patients at 10 years was only 20.8%. Lung metastasis determined the prognosis.


Endometrial preparation and maternal and obstetrical outcomes after frozen blastocyst transfer.
Two types of endometrial preparation protocols are used for frozen embryo transfers in current practice: hormone replacement and the natural cycle. Endometrial preparation in the natural cycle reportedly increases the chances of live birth and decreases early pregnancy loss compared with that in the hormone replacement cycle. However, the influence of endometrial preparation on maternal and neonatal health remains unclear. This study aimed to investigate whether the differences between hormone replacement cycle and natural cycle influence perinatal outcomes and risk of congenital anomalies in frozen-thawed blastocyst transfer fetuses or births. Perinatal outcomes and congenital abnormalities were compared between the natural and hormone replacement cycles. According to the timing of ovulation, frozen-thawed blastocyst transfers in the natural cycle were classified into 2 patterns: on day 4.5 (ovulation 4.5) or day 5 (ovulation 5.0) after ovulation. When the serum luteinizing hormone level was not increased on the day of the trigger, a single vitrified-warmed blastocyst transfer was performed on day 7 after the trigger (ovulation 5.0). When the luteinizing hormone level was slightly increased on the day of trigger, single vitrified-warmed blastocyst transfer was performed on day 6 after the trigger (ovulation 5.0). In total, 67,018 cycles (ovulation 4.5, 29,705 cycles; ovulation 5.0, 31,995 cycles; hormone replacement, 5318 cycles) of frozen-thawed blastocyst transfer between January 2008 and December 2017 at Kato Ladies Clinic were retrospectively analyzed. During the study period, embryo cryopreservation was performed using a vitrification method in all cycles. Hormone replacement cycles were associated with a higher occurrence of hypertensive disorders of pregnancy (adjusted odds ratio, 2.16; 95% confidence interval, 1.66-2.81) and placenta accreta (adjusted odds ratio, 4.14; 95% confidence interval, 1.64-10.44) compared with the natural cycle. The risks of cesarean delivery (adjusted odds ratio, 1.93; 95% confidence interval, 1.78-2.18), preterm birth (adjusted odds ratio, 1.55; 95% confidence interval, 1.25-1.93), and low birthweight (adjusted odds ratio, 1.42; 95% confidence interval, 1.18-1.73) were also higher for hormone replacement cycles. No significant difference in the risk of congenital anomalies was observed between the 2 cycles. The risk of hypertensive disorders of pregnancy, placenta accreta, cesarean delivery, preterm delivery, and low birthweight was higher in hormone replacement cycles than in natural cycles, whereas the risk of congenital anomalies was similar between both cycles. Further follow-up is needed to investigate these risks and to explore alternative endometrial preparation methods.


Distribution of 137Cs, 238Pu and 239+240 Pu in sediments of the southeastern Brazilian shelf-SW Atlantic margin.
In this work levels of 137Cs, 238Pu and 239+240 Pu as well as activity ratios of anthrophogenic radionuclides in sediment samples from the southeastern Brazilian shelf are presented. Instrumental gamma spectrometry was used to determine 137Cs and alpha spectrometry to determine 238Pu and 239+240 Pu after a radiochemical procedure. The levels ranged from 0.30 to 1.79 Bq kg(-1) for 137Cs, from 15 to 150 mBq kg(-1) for 238Pu and, from 18 to 117 mBq kg(-1) for 239+240 Pu. There was a bathymetric differentiation in the radionuclides distribution. 137Cs values were generally higher in the samples collected at water depths of less than 100 m. On the other hand, plutonium isotopes exhibit higher values at greater depths. The mean ratio of 239+240 Pu/137Cs obtained was 0.112+/-0.072 which is in agreement with the value reported for the Atlantic from atmospheric fallout of nuclear explosions in the past. The 238Pu/230+240 Pu ratios varied widely (from 0.339 to 2.088) and showed the influence of the SNAP-9A accident in the 238Pu levels for this area. The main goal of this work was to present unpublished anthropogenic radionuclide levels and activity ratios related to the contamination of the southeastern Brazilian shelf.


Treatment and outcomes of lateral collateral ligament injury associated with anterior and posterior cruciate ligament injury at 2-year follow-up.
Injuries to the lateral collateral ligament (LCL) are most commonly associated with anterior cruciate ligament (ACL) injury than with posterior cruciate ligament (PCL) injury. There is currently a paucity in the literature in regards to treatment and outcomes of such lesions. 30 patients underwent surgical treatment of concomitant LCL and ACL injury or concomitant LCL and PCL injury with follow-up postoperative period of two years. The Lysholm score and varus stress radiographs was calculated and analysed before and at 6, 12, and 24 months postoperatively. There was a significant increase in scores between two timepoints over the follow-up period for both groups: before surgery and after 6 months, and between 6 and 12 months (p < 0.05). The lateral joint opening measured on the varus stress radiographs was greater in group 2 than in group 1 before surgery (p = 0.04). When assessing each group separately, the lateral joint opening decreased at each timepoint in the first year for both groups (p < 0.05). Patients diagnosed with combined LCL and PCL injuries were shown to have a higher degree of lateral opening at the time of injury when compared to patients with combined LCL and ACL injuries. However, there was no difference in lateral joint opening on stress radiography after 12 months postoperatively in either group. Finally Lysholm scores for both groups significantly increased between the preoperative period and 6 months postoperatively, as well as between 6 months and 12 months postoperatively. III.


Prenatal stress and early life febrile convulsions compromise hippocampal genes MeCP2/REST function in mid-adolescent life of Sprague-Dawley rats.
Early life neuronal insults exacerbate the development of febrile seizures and can result in epigenetic changes in the hippocampus. The MeCP2 and REST genes play a pivotal role in cognition as both contribute to neuronal function. In this study, cognitive function and expression of the MeCP2 and REST genes in the hippocampus were investigated in four groups of Sprague Dawley rats offspring viz. (1) Normally reared treated with saline (NSS). (2) Prenatally stressed treated with saline (SS). (3) Normally reared with febrile seizures (NSFS). (4) Prenatally stressed with febrile seizures (SFS). Pregnant dams were subjected to 1h of restraint stress for 7days starting on gestational day 14. Following birth, a once-off exposure to saline injections or febrile seizure induction was conducted on postnatal day (PND) 14. Behavioural tests were conducted using the Morris-Water maze on PND 21 and 30. Our results showed a febrile seizure effect on learning and memory in the non-stressed animals. However, febrile seizures did not exacerbate learning deficits in the prenatally stressed animals. Gene analysis found a down-regulation in MeCP2 gene expression and an up-regulation of the REST gene in prenatally stressed animals. Exposure to febrile seizure resulted in down-regulation of both MeCP2 and REST gene expression in the non-stressed animals, but febrile seizures did not exacerbate the stress effect on gene expression. This suggests that exposure to prenatal stress (SS) and febrile seizures (NSFS) may impair cognitive behavioural function. However, in the NSFS animals, there seems to be an attempt to counteract the effects of febrile seizures with time.


Management of a Patient With Premenstrual Syndrome Using Acupuncture, Supplements, and Meditation: A Case Report.
The purpose of this case report was to describe a multimodal approach for the treatment of premenstrual syndrome (PMS). A 36-year-old nulliparous woman presented to a free clinic for veterans and their spouses. She received a PMS diagnosis at age 18. She was previously prescribed hormonal birth control and nonsteroidal anti-inflammatory drugs, which minimally affected her condition. She stopped using conventional medicine therapies at age 27. Laboratory results showed that her progesterone was below 0.5 ng/mL. Her symptom score was 50 out of 60 on the Treatment Strategies for PMS assessment tool. During her menses, she experienced low back pain and stiffness, bloating, swelling, weight gain, breast tenderness, swelling, and pain, and she felt overwhelmed and stressed. Traditional Chinese medicine acupuncture was administered in conjunction with 100 mg of coenzyme Q10 (ubiquinol) and a B-100 complex once a day and 400 mg of magnesium citrate, 1000 mg of flaxseed oil (Linum usitatissimum), and 1000 mg of turmeric (Curcuma longa) twice a day. Five days before the onset of her menstrual period, she was to ingest a B-100 complex twice a day and 400 mg of magnesium citrate, 1000 mg of flaxseed oil, and 1000 mg of turmeric 3 times a day. Mindfulness meditation was encouraged twice a day for 10 minutes to reduce stress. After 12 treatments over 3 months, her symptom score decreased to 18 out of 60 and remained below 20 for an additional 32 weeks. This patient with PMS symptoms positively responded to a multimodal approach using traditional Chinese medicine-style acupuncture, dietary supplements, and mindfulness meditation.


Long-lived Ames dwarf mice: Oxidative damage to mitochondrial DNA in heart and brain.
The single gene mutation of Ames dwarf mice increases their maximum longevity by around 40% but the mechanism(s) responsible for this effect remain to be identified. This animal model thus offers a unique possibility of testing the mitochondrial theory of aging. In this investigation, oxidative damage to mitochondrial DNA (mtDNA) was measured for the first time in dwarf and wild type mice of both sexes. In the brain, 8-oxo,7,8-dihydro-2'-deoxyguanosine (8-oxodG) in mtDNA was significantly lower in dwarfs than in their controls both in males (by 32%) and in females (by 36%). The heart of male dwarfs also showed significantly lower mtDNA 8-oxodG levels (30% decrease) than the heart of male wild type mice, whereas no differences were found in the heart of females. The results, taken together, indicate that the single gene mutation of Ames dwarfs lowers oxidative damage to mtDNA especially in the brain, an organ of utmost relevance for aging. Together with the previous evidence for relatively lower level of oxidative damage to mtDNA in both long-lived and caloric restricted animals, these findings suggest that lowering of oxidative damage to mtDNA is a common mechanism of life extension in these three different mammalian models.


Implementation of an evidence-based intervention to promote colorectal cancer screening in community organizations: a cluster randomized trial.
The implementation of evidence-based strategies to promote colorectal cancer (CRC) screening remains challenging. The aim of this study is to evaluate two strategies to implement an evidence-based intervention to promote CRC screening in Filipino American community organizations. Twenty-two community organizations were randomized to either a basic or enhanced implementation strategy. In both arms, community health advisors recruited participants non-adherent to CRC screening guidelines, conducted educational sessions, distributed print materials and free fecal occult blood test kits, reminded participants to get screened, and mailed letters to participants' providers. In the enhanced arm, leaders of the organizations participated in implementation efforts. While the effectiveness was similar in both arms of the study (screening rate at 6-month follow-up was 53 % in the enhanced arm, 49 % in the basic arm), 223 participants were screened in the enhanced arm versus 122 in the basic arm. The enhanced implementation strategy reached 83 % more participants and achieved a higher public health impact. NCT01351220 (ClinicalTrials.gov).


Complex arming in antibody-dependent cell-mediated cytotoxicity: ultrastructural studies of the interaction between human effector cells armed with aggregated anti-DNP antibody and DNP-coated erythrocytes.
We have examined, by transmission electron microscopy, mixtures of DNP-coated chicken red blood cells and normal human peripheral blood leucocytes 'armed' with alkali-aggregated anti-dinitrophenyl (DNP) antibody. The combination of these observations with chromium release assays enabled us to identify four types of effector cell interacting with the target erythrocytes, viz. phagocytic and non-phagocytic monocytes, neutrophils and lymphocytes. Comparison of these findings with previous work, using antibody-coated targets, allowed us to conclude that the mechanisms and cell types involved are similar. We also demonstrated the short-lived cytotoxic potential of cells armed in this manner.


Multidrug resistance, biofilm formation and detection of bla CTX-M and bla VIM genes in E. coli and Salmonella isolates from chutney served at the street-food stalls of Bharatpur, Nepal.
Antimicrobial resistance (AMR) amid the bacteria found in ready-to-eat foods is a grave concern today warranting an immediate intervention. The current study was undertaken to explore the status of AMR in E. coli and Salmonella species in ready-to-eat Chutney samples (n = 150) served at the street food stalls in Bharatpur, Nepal, with a major focus on detecting extended-spectrum β-lactamase (ESBL) and metallo β-lactamase (MBL) genes along with biofilm formation. Average viable counts, coliform counts, and Salmonella Shigella counts were 1.33 × 106±141481.4, 1.83 × 105±91303.6, and 1.24 × 105±63933.19 respectively. Out of 150 samples, 41 (27.33%) harbored E. coli, of which 7 were E. coli O157:H7; whereas Salmonella spp. were found in 31 (20.67%) samples. Bacterial contamination of Chutney by E. coli and Salmonella and ESBL-production were both found significantly affected by different sources of water used, personal hygiene and literacy rate of the vendors as well as by the type of cleaning materials used to wash knives and chopping boards (P < 0.05). Antibiotic susceptibility testing revealed that imipenem was the most effective drug against both types of bacterial isolates. Additionally, 14 (45.16%) Salmonella isolates and 27 (65.85%) E. coli isolates were found to be multi-drug resistant (MDR). Total ESBL (bla CTX-M) producers reported were 4 (12.90%) Salmonella spp. and 9 (21.95%) E. coli. Only 1 (3.23%) Salmonella spp. and 2 (4.88%) E. coli isolates were bla VIM gene carriers. Dissemination of knowledge of personal hygiene amongst the street vendors and consumer awareness regarding ready-to-eat foods are crucial factors that can be suggested to curtail the emergence and transmission of food-borne pathogens.


Single immunization with a recombinant multiple-epitope protein induced protection against FMDV type Asia 1 in cattle.
To develop recombinant epitope vaccines against the foot-and-mouth disease virus (FMDV) serotype Asia 1, genes encoding six recombinant proteins (A1-A6) consisting of different combinations of B-cell and T-cell epitopes from VP1 capsid protein (VP1) of FMDV were constructed. These proteins were expressed in Escherichia coli and used to immunize animals. Our results showed that A6 elicited higher titers of neutralizing antibodies after single inoculation in guinea pigs than did the other five recombinant proteins, as determined by micro-neutralization tests. In addition, a strong lymphocyte proliferation response and Th1 type immunity were observed in splenocytes from the mice immunized with A6. Further tests carried out in cattle demonstrated that a single inoculation with A6 generated comparable levels of neutralizing antibodies as inactivated vaccine and protected 4 of 5 cattle against challenge with FMDV type Asia 1. Our results suggest that A6 might be a promising recombinant vaccine against FMDV type Asia 1 in cattle.


Ureteroneocystostomy without dissection of the submucosal tunnel.
A technique of ureteroneocystostomy with fixation of the ureter to the bladder musculature denuded from the mucosa was studied in dogs. The intravesical portion of the ureter shrank to half its original length after the operation. This portion preserved its muscular structure and was overgrown by the bladder mucosa to more than half its circumference. The submucous canal thus formed for the ureter prevented reflux in every animal. The technique avoids the formation of strictures. It is recommended if direct dissection of a submucous canal is impracticable.


Disturbed bowel habits in patients with non-ulcer dyspepsia.
BACKGROUND; Emerging medications for non-ulcer-dyspepsia, such as the serotonin-receptor modulators, also affect bowel habits by altering colonic transit. If drugs that alter colonic function were to prove useful in non-ulcer dyspepsia, knowledge of baseline bowel habit disturbances would be potentially critical. To estimate the rate of non-ulcer dyspepsia patients with clinically relevant constipation or diarrhoea potentially precluding use of motility agents. Consecutive patients with non-ulcer dyspepsia (n = 79), gastro-oesophageal reflux disease (n = 135) and organic upper gastrointestinal disease (upper gastrointestinal disease; n = 36) completed a validated symptom questionnaire evaluating predominant bowel habits in the last year. Prevalence of constipation was higher in non-ulcer dyspepsia (34%) than in gastro-oesophageal reflux disease (P = 0.01) and organic upper gastrointestinal disease (P = 0.01), prevalence of alternating diarrhoea/constipation (24%) and diarrhoea (22%) was similar, while prevalence of normal bowel habits was significantly less in non-ulcer dyspepsia (20%; P = 0.01 vs. gastro-oesophageal reflux disease and P < 0.01 vs. organic upper gastrointestinal disease). Constipation was particularly frequent in ulcer-like and dysmotility-like non-ulcer dyspepsia, while prevalence of diarrhoea was lowest in dysmotility-like non-ulcer dyspepsia. A normal bowel habit was equally uncommon in male (21%) and female non-ulcer dyspepsia patients (20%). Only one of five non-ulcer dyspepsia patients had normal bowel habits based on clinical symptoms; constipation is particularly prevalent. Patients with functional dyspepsia who are prescribed motility altering drugs should be evaluated by taking a thorough bowel habit history.


Preferences of dress and address: views of attendees and mental health professionals of the psychiatric services.
The aim of this study was to determine the views of both individuals attending the mental health services (attendees) and mental health professionals in relation to how attendees and staff should be addressed, how attendees should be described, and how staff should be attired. We surveyed 132 attendees of the West Galway Mental Health Services and 97 mental health professionals in relation to how they prefer to be addressed (first name/ title and surname/ no preference) the description of attendees (patient / client / service user / no preference) and the attire of mental health staff (casual / smart / no preference). We also ascertained how mental health professionals believed attendees would view these issues. Attendees preferred to be described as patients rather than clients or service users by all mental health professionals, with 46-54% of attendees preferring this term "patient" compared to 14-17% preferring the term "client", 11-13% preferring the term "service user" and 20-25% having no preference (p < 0.001). They preferred to address doctors by their title and surname (61%) but other mental health professionals by their first names (60-69%) (p < 0.001). Attendees had a strong preference for being addressed by their first names by all the mental health professionals (86-91%) (p < 0.001). Doctors preferred to be attired formally (88%), compared to nurses (50%) or other mental health professionals (42%) (p = 0.002). Attendees had no preference in relation to the attire of doctors but preferred other mental health professionals to be attired informally. The study demonstrates that despite the increased use of several non-medical terms to describe attendees of mental health services; the preferred term of attendees of the psychiatric services in both in-patient and out-patient settings remains 'patient'. However, this is not universally the case, and the ascertainment of the preference of the attendee at the first encounter with the health professional should be ascertained. We also demonstrated that attendees preferences in relation to both "dress and address" of doctors is significantly different to their preference for nurses or other allied mental health professionals; which may reflect a wish for a less familiar and more formal interaction with doctors.