Efficacy of the Fun For Wellness Online Intervention to Promote Well-Being Actions: A Secondary Data Analysis.
Fun For Wellness (FFW) is a new online intervention designed to promote growth in well-being by providing capability-enhancing learning opportunities (e.g., play an interactive game) to participants. The purpose of this study was to provide an initial evaluation of the efficacy of the FFW intervention to increase well-being actions. The study design was a secondary data analysis of a large-scale prospective, double-blind, parallel-group randomized controlled trial. Data were collected at baseline and 30 and 60 days postbaseline. A total of 479 adult employees at a major university in the southeast of the United States of America were enrolled. Participants who were randomly assigned to the FFW group were provided with 30 days of 24-hour access to the intervention. A two-class linear regression model with complier average causal effect estimation was fitted to well-being actions scores at 30 and 60 days. Intent-to-treat analysis provided evidence that the effect of being assigned to the FFW intervention, without considering actual participation in the FFW intervention, had a null effect on each dimension of well-being actions at 30 and 60 days. Participants who complied with the FFW intervention, however, had significantly higher well-being actions scores, compared to potential compliers in the Usual Care group, in the interpersonal dimension at 60 days, and the physical dimension at 30 days. Results from this secondary data analysis provide some supportive evidence for both the efficacy of and possible revisions to the FFW intervention in regard to promoting well-being actions.


Thrombotic Thrombocytopenic Purpura Masquerading as Acute Ischemic Stroke.
Thrombotic thrombocytopenic purpura (TTP) is a hematologic disorder that results in widespread clotting due to a deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) protease. This leads to excessive von Willebrand factor (VWF) protein-platelet multimers. Due to platelet consumption, platelet levels fall, resulting in thrombocytopenia. We examined a case of a 31-year-old female with no significant medical history who presented with expressive aphasia and paresthesias and was sent to the Emergency Department for a stroke workup. Imaging was negative for ischemic or hemorrhagic stroke; however, a complete blood count (CBC) was consistent with anemia and thrombocytopenia, resulting in a high suspicion for TTP. She was admitted to the intensive care unit and given fresh frozen plasma and packed red blood cells. Plasma exchange therapy was initiated, and her aphasia and paresthesias began to improve. The ADAMTS13 level returned at less than 5%, which prompted the initiation of rituximab therapy. During her 36-day hospital stay, she continued to receive daily steroids and plasma exchange and a total of four courses of rituximab. Her platelets steadily climbed, and she was discharged with instructions to follow up with outpatient hematology. TTP is a thrombotic microangiopathy that results in microscopic blood clots anywhere in the body, including the cerebral arteries. This results in the neurologic abnormalities that are often seen in TTP. Because TTP is a rare disease, treatment modalities are still scarce but include steroids, plasma exchange therapy, and rituximab. Novel therapies are on their way, one being caplacizumab, a monoclonal antibody that inhibits VWF from interaction with glycoprotein 1b. A concern highlighted by this case is the exclusion criteria for the administration of tissue plasminogen activator (TPA). As this patient presented with stroke symptoms and a negative head CT, TPA would have been administered had a CBC not returned showing evidence of TTP. This highlights the importance of strict adherence to the American Heart Association/American Stroke Association guidelines that include ensuring that the platelet count is >100,000 prior to the initiation of TPA.


An improved apparatus for transscleral iontophoresis of gentamicin.
The authors previously found that positively charged substances are less well-transported into the vitreous humor by transscleral iontophoresis than are negatively charged substances. There was more bubble formation in the eye cup with positively charged than with negatively charged substances. The authors hypothesized that these bubbles might account for the poorer conductance of the positively charged species by causing interruptions of the current. Therefore, the authors developed a modified eye cup in which the diameter of the fluid column was larger than that in the old device (1.0 rather than 0.5 mm). This modification allowed larger voltage to be applied than with the older device, because bubbles could be more easily cleared from the conjunctiva than with the narrower-bore eye cup. Although the efficiency of the apparatus was the same with the two eye cups (micrograms per milliliter in vitreous humor divided by milliampere minutes of current applied), vitreal concentrations of gentamicin with the modified eye cup were fourfold higher than with the older eye cup (83 versus 19 micrograms/ml; P < 0.001). These studies suggest that modifying the eye cup to permit easier removal of bubbles resulted in improved delivery of gentamicin into the ocular humors.


Genetic etiology of stability of attention problems in young adulthood.
Variation in attention problems in children and adolescents from non-clinical samples is highly heritable. It is unknown how attention problems develop later in life and whether the heritability in the general adult population is the same as in children and adolescents. We assessed the heritability and stability of individual differences in attention problems in the general young adult population and explored to what extent the stability can be attributed to genetic or environmental factors. On one or more occasions, young adult twins (age range, 18-30 years, N = 4,245) from the Netherlands Twin Registry filled out the attention problems (AP) subscale of the Young Adult Self-Report [Achenbach, 1997]: in 1991, N = 1,755 (of which 842 complete pairs), in 1995, N = 2,428 (1156 complete pairs) and in 1997, N = 2,344 (958 pairs). There was only a slight decrease in the average level of attention problems during young adulthood. The heritability at each occasion was around 40%. The correlation of attention problems across a period of 6 years was 0.42, and 77% of this correlation could be ascribed to genetic influences. Thus, individual differences in attention problems in young adulthood are heritable, and stability in individual differences over time can largely be ascribed to genetic influences. Genetic correlations across time were high, suggesting that the genes that influence variability in attention problems in late adolescence are largely the same as those that influence variability in early adulthood.


Nuclear magnetic resonance spectroscopy reveals the metabolic origins of proline excreted by an Escherichia coli derivative during growth on [13C]acetate.
We have used 13C nuclear magnetic resonance to monitor acetate metabolism in a proline-overproducing strain of Escherichia coli growing on 13C-labeled acetate. The conversion of 13C-labeled acetate to proline by actively dividing cells was followed in vivo, and the site specificity of the incorporation of the acetate carbons in the proline was determined from spectra of butanol extracts of the growth media. The degree of incorporation of deuterium from partially deuterated water into various sites on the proline was monitored from the beta-deuterium-shifted signals in the 13C spectra. The spectra provide information on the origin of the carbons and the protons during proline biosynthesis.


Continued nursing education in low-income and middle-income countries: a narrative synthesis.
Continued nursing education and development can reduce mortality and morbidity of patients and can alleviate the shortage of healthcare workers by training of nurses for high-demand skill sets. We reviewed patterns of educational interventions and strategies in initiating behaviour change, improving patient outcomes or knowledge for nurses in low- and middle-income countries (LMICs). The study searched the MEDLINE (PubMed), Embase, CINAHL, Google Scholar and Web of Science databases. The study included interventional studies on continued nursing education from 2007 to 2017. Of the 6216 publications retrieved, 98 articles were included and analysed by three independent reviewers. Of the 98 studies that met inclusion criteria, five were randomised controlled trials, two were qualitative in design and the remaining 91 were quasi-experimental, before-and-after studies. Of these studies, the median sample size of participants was 64, and the majority were conducted in Asia (53.1%). During the 10-year study period, 20.4% was conducted in 2015, the highest proportion, with a general increase in number of studies over time from 2007 to 2017. Main themes that arose from the review included train-the-trainer models, low-dose/high-frequency models, use of multiple media for training, and emphasis on nurse empowerment, strong international partnerships, and the integration of cultural context. Overall, the studies were limited in quality and lacked rigorous study design. Continued nursing education in LMICs is essential and effective in improving nurses' knowledge base, and thus patient outcomes and quality of care. Long-term, randomised studies are needed to understand how training strategies compare in impact on nurses and patients.


[Features of changes in the electrochemical properties of water activated with structurally stressed calcium carbonate in micellar form].
The results of studies of electrochemical indices of waters activated with structurally stressed calcium carbonate tension in micellar form during storage are presented and these indicators of water were shown to change over time. In this case, waters, having initially superior activity over time reduce it, giving place to the waters that have at this moment an activity greater than the activity of the sample leading at the beginning. Established that the cause of this oscillatory over time change in activity is a non-local interaction between macroscopic quantum systems of activated waters located at a distance from each other. Oscillatory changes of the electrochemical indices of activated water during storage reflect the dynamic of changes in its biological properties. These changes in the electrochemical indices should be considered in evaluation of the structural and energetic state of the activated water during storage by means of introducing the correction factors.


Regional distribution of the anticonvulsant and behavioural effects of muscimol injected into the substantia nigra of rats.
Previous anatomical investigations have reported a direct projection from substantia nigra pars lateralis to the dorsal midbrain anticonvulsant zone. The present study tested the hypothesis that the anticonvulsant properties of nigral inhibition previously attributed to substantia nigra pars reticulata were, in fact, due to the suppression of neural activity in the adjacent pars lateralis. Using the electroshock model of epilepsy, a systematic map of the anticonvulsant effects of bilateral injections of muscimol (60 ng/0.5 mu l per side) into different parts of substantia nigra was constructed. Electroshock (1 s of 40 mA 50 Hz AC) was administered via ear-clip electrodes 5 or 60 min following injections of muscimol, or 60 min after control injections of saline. To provide insight into the functional mechanisms whereby nigral inhibition might suppress tonic seizures the behavioural effects elicited by muscimol were also noted. No evidence supporting the experimental prediction was found. The most sensitive region of substantia nigra for suppressing tonic hindlimb extension was caudal pars reticulata. These data indicate a serious mismatch between the results of microinjection mapping studies and underlying patterns of anatomical connectivity. The behavioural reaction most closely associated with tonic seizure suppression was stereotyped locomotion; both were obtained maximally from caudal pars reticulata. Rostral substantia nigra was associated more with oral stereotypy, while a raised head position was observed at lateral injection sites and a lowered positioning of the head at medial locations. These data suggest that the rat substantia nigra may contain a functional organization based on a form of somatomotor topography. This organization may influence which part of the substantia nigra is most effective in suppressing seizures expressed by different muscle groups of the body.


Long-term visual outcome in patients treated by flow diversion for carotid-ophthalmic aneurysms.
Flow-diverter stents (FDSs) are an upgrade in the treatment of intracranial aneurysms. However, complications concerning covered branches have been reported, especially the ophthalmic artery (OA). The purpose of our study was to evaluate the long-term ophthalmic complication rate of carotid-ophthalmic aneurysms (COA) without visual pathways compression, treated by a FDS covering the OA by performing an exhaustive ophthalmic examination. Retrospective analysis of a single-center database screening the patients treated from October 2009 to April 2015 for an intracranial aneurysm with a FDS. The patients treated for a non-compressive COA with coverage of the OA by the device were studied (n=30). Among these patients, 15 (50%) were excluded. The remaining 15 patients underwent a systematic and extensive ophthalmic examination at least 2 years after the stent placement by two ophthalmologists. Fifteen patients with 16 COAs treated with a FDS were included. Mean follow-up was 4.1±2 years. Six patients (40%), presented ophthalmic complications, including three fugax amauroses (18.8%) and four significant visual field defects (25%). After comparing each eye's visual field's patients, we observed a significant difference between the eye on the FDS side compared with the contralateral eye, with a mean deviation of -1.58 dB versus -0.67 dB respectively (P=0.003). Visual acuity was preserved in all patients. Patients treated by FDS for COA have a good long-term clinical ophthalmic outcome. However, extensive ophthalmic examination shows a high percentage of minor ophthalmic modifications. Interventional neuroradiologists should be aware of these possible complications when choosing to treat these aneurysms with FDS.


[Musculoskeletal tumor evaluation with 99mTc-Tetrofosmin].
(99m)Tc-tetrofosmin is an efficient agent as a tumor marker. Several studies have proven its efficiency in detection and localization of tumors of the breast, larynx, thyroid, parathyroid glands, lung, brain, skin, lymphatic and musculoskeletal tissues with a sensitivity and specificity of 95% to 100%. It is used as a predictor of therapy efficacy and to localize remaining and recurrent tissue as well as local and distant extension. To determine the sensitivity, specificity and predictive values of the three-phase 99mTc-Tetrofosmin scan in detection of malignant lesions of the musculoskeletal tissue. Seventy-three patients of both genders with suspected malignant musculoskeletal lesions were studied by three-phase (vascular, tissue and delayed images) 99mTc-tectrofosmin scans. One-hundred-percent sensitivity, 67.3% specificity, 55% positive predictive value, and 100% negative predictive value. Three-phase 99mTc-tectrofosmin scan is useful in detection of malignant lesions of the musculoskeletal system due to its high sensitivity and positive predictive value. Nevertheless, benign pathology such as active inflammation is a source of false positives and the attending physician must consider the aid of complementary studies such as histopathology.


Identifying Rates of Meadowfoam (Limnanthes alba) Seed Meal Needed for Suppression of Meloidogyne hapla and Pythium irregulare in Soil.
Meadowfoam (Limnanthes alba) is a commercial oilseed annual crop grown in Oregon. After extracting oil from seed, the remaining seed meal is rich in the secondary plant metabolite glucolimnanthin, which can be converted into pesticidal compounds such as 3-methoxybenzyl isothiocyanate (ITC) and 3-methoxyphenylacetonitrile (nitrile) in the presence of the enzyme myrosinase. In previous studies, we demonstrated that ITC and nitrile, produced by mixing freshly ground meadowfoam seed with meadowfoam seed meal, are toxic to the plant-parasitic nematode Meloidogyne hapla and the plant pathogen Pythium irregulare. In this study, we evaluated factors that might influence the implementation of meadowfoam seed meal into agricultural production systems for soilborne pathogen and nematode control. Rate-finding experiments demonstrated that a minimum 1.0% seed/seed meal formulation (wt/wt) was necessary to achieve nematode and pathogen suppression; seed meal alone was insufficient for complete control of M. hapla and stimulated the growth of P. irregulare. When this 1.0% seed/seed meal formulation was used, a greater soil amendment rate was required to cause 100% mortality of P. irregulare (1.0% wt/wt) than for M. hapla (0.5% wt/wt). In phytotoxicity experiments, soil amended with the 1.0% seed/seed meal formulation was consistently phytotoxic to wheat, cucumber, and tomato. However, phytotoxic effects were mitigated by a delayed planting into the amended soil. A final assay to monitor concentrations of ITC and nitrile in conjunction with assessing M. hapla and P. irregulare mortality was conducted over a 6-day period in soils amended at 0.5 and 1.0% (wt/wt) with the 1.0% seed/seed meal formulation. The response was rapid, with 100% mortality of both organisms within 2 h after exposure to amended soil. Concentrations of nitrile remained relatively constant over the 6-day period (approximately 0.017 and 0.032 mg/ml at 0.5 and 1.0% amendment rates, respectively), whereas ITC production increased rapidly and peaked 12 to 24 h after amendment (0.083 and 0.171 mg/ml at 0.5 and 1.0% amendment rates, respectively) before returning to near undetectable levels.


Salivary Antiviral and Antibacterial Properties in the Encounter of SARS-CoV-2.
Due to the high mortality rate of COVID-19 and its high variability and mutability, it is essential to know the body's defense mechanisms against this virus. Saliva has numerous functions, such as digestion, protection, and antimicrobial effects. Salivary diagnostic tests for many oral and systemic diseases will be available soon because saliva is a pool of biological markers. The most important antiviral and antibacterial compounds identified in saliva include lysozyme, lactoferrin (LF), mucins, cathelicidin, salivary secretory immunoglobulin (SIgA), chromogranin A, cathelicidin, salivary agglutinin (SAG) (gp340, DMBT1), α, β defensins, cystatin, histatins, secretory leukocyte protease inhibitor (SLPI), heat shock protein (HSP), adrenomedullin and microRNA (miRNAs). Antimicrobial peptides (AMPs) in saliva could be used in the future as models for designing effective oral microbial antibiotics. The antiviral properties of the peptides in saliva may be one of the future treatments for the COVID-19 virus. In this review, we investigate compounds with antiviral and antibacterial properties in saliva and the importance of these compounds in saliva in exposure to the COVID-19 virus. Due to the transmission route of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) into the oral cavity in the lower and upper respiratory tract, studies of salivary antiviral properties in these patients are very important. Some of the antiviral effects of saliva, especially mucin, α, β-defensins, IgA, IgG, IgM, lysozyme, SAG, SLPI, and histatins, may play a greater role in neutralizing or eliminating COVID-19.


Application of GC-MS/MS for the analysis of tobacco alkaloids in cigarette filler and various tobacco species.
This publication reports the first known use of gas chromatography-tandem mass spectrometry for the quantitation of five minor tobacco alkaloids (nornicotine, myosmine, anabasine, anatabine, and isonicoteine) in various tobacco samples. A summary of the concentrations of these minor alkaloid levels in the filler from 50 popular cigarette brands were found to be 659-986 μg/g nornicotine, 8.64-17.3 μg/g myosmine, 127-185 μg/g anabasine, 927-1390 μg/g anatabine, and 23.4-45.5 μg/g isonicoteine. Levels of minor alkaloids found in reference cigarettes (1R5F, 2R4F, 3R4F, CM4, and CM6) as well as burley, flue-cured, oriental, reconstituted, and Nicotiana rustica and Nicotiana glauca tobacco types are also reported. Quantitation of the minor tobacco alkaloids is important because the alkaloids have been shown to be precursors of carcinogenic tobacco specific N'-nitrosamines.


Factors affecting the decision to rehabilitate the posterior maxilla following surgical closure of oroantral communications/fistulae - A cohort study.
Search of the English literature yielded no studies assessing the chosen dental treatment following surgical closure of oroantral communication/oroantral fistula (OAC/OAF). The purpose of the present study was to assess factors affecting the decision to rehabilitate the posterior maxilla following surgical closure of OAC/OAF. Consecutive patients at a single center. A structured form served to collect the data. The differences between groups (cases with versus cases without restoration) were assessed statistically. A total of 58/121 responding individuals (62.1% men). Average age 51.57 years. Average waiting time prior to restoration 10.34 months. Most (51.7%) healthy. Most had a dental etiology (60.3%). Thirty-nine (67.2%) patients had a restoration of the posterior maxilla. Most of the patients responded that the reason not to do any restoration is the fear of failure (65.5%). Most of the patients completed the restoration procedure in a private clinic (87.2%). Only one patient (2.6%) reported a complication. Approximately half of the patients had implant supported prosthesis (ISP) following sinus augmentation (48.3%) with delayed implant placement. Most of the patients responded that the reason not to have ISP was the fear of failure (72.7%), and the rest responded because of financial issues (27.3%). For tooth supported restoration, most of the patients responded removable (90.9%). Surgeons generally wait 6-12 months following surgical treatment of OAC/OAF prior to reconstruction with ISP. The chance for complications is low. Healthy women after dental induced OAC/OAF have the highest chances to seek for ISP in such circumstances.


An essential role for Fgfs in endodermal pouch formation influences later craniofacial skeletal patterning.
Fibroblast growth factor (Fgf) proteins are important regulators of pharyngeal arch development. Analyses of Fgf8 function in chick and mouse and Fgf3 function in zebrafish have demonstrated a role for Fgfs in the differentiation and survival of postmigratory neural crest cells (NCC) that give rise to the pharyngeal skeleton. Here we describe, in zebrafish, an earlier, essential function for Fgf8 and Fgf3 in regulating the segmentation of the pharyngeal endoderm into pouches. Using time-lapse microscopy, we show that pharyngeal pouches form by the directed lateral migration of discrete clusters of endodermal cells. In animals doubly reduced for Fgf8 and Fgf3, the migration of pharyngeal endodermal cells is disorganized and pouches fail to form. Transplantation and pharmacological experiments show that Fgf8 and Fgf3 are required in the neural keel and cranial mesoderm during early somite stages to promote first pouch formation. In addition, we show that animals doubly reduced for Fgf8 and Fgf3 have severe reductions in hyoid cartilages and the more posterior branchial cartilages. By examining early pouch and later cartilage phenotypes in individual animals hypomorphic for Fgf function, we find that alterations in pouch structure correlate with later cartilage defects. We present a model in which Fgf signaling in the mesoderm and segmented hindbrain organizes the segmentation of the pharyngeal endoderm into pouches. Moreover, we argue that the Fgf-dependent morphogenesis of the pharyngeal endoderm into pouches is critical for the later patterning of pharyngeal cartilages.


Bending fluctuations in semiflexible, inextensible, slender filaments in Stokes flow: Toward a spectral discretization.
Semiflexible slender filaments are ubiquitous in nature and cell biology, including in the cytoskeleton, where reorganization of actin filaments allows the cell to move and divide. Most methods for simulating semiflexible inextensible fibers/polymers are based on discrete (bead-link or blob-link) models, which become prohibitively expensive in the slender limit when hydrodynamics is accounted for. In this paper, we develop a novel coarse-grained approach for simulating fluctuating slender filaments with hydrodynamic interactions. Our approach is tailored to relatively stiff fibers whose persistence length is comparable to or larger than their length and is based on three major contributions. First, we discretize the filament centerline using a coarse non-uniform Chebyshev grid, on which we formulate a discrete constrained Gibbs-Boltzmann (GB) equilibrium distribution and overdamped Langevin equation for the evolution of unit-length tangent vectors. Second, we define the hydrodynamic mobility at each point on the filament as an integral of the Rotne-Prager-Yamakawa kernel along the centerline and apply a spectrally accurate "slender-body" quadrature to accurately resolve the hydrodynamics. Third, we propose a novel midpoint temporal integrator, which can correctly capture the Ito drift terms that arise in the overdamped Langevin equation. For two separate examples, we verify that the equilibrium distribution for the Chebyshev grid is a good approximation of the blob-link one and that our temporal integrator for overdamped Langevin dynamics samples the equilibrium GB distribution for sufficiently small time step sizes. We also study the dynamics of relaxation of an initially straight filament and find that as few as 12 Chebyshev nodes provide a good approximation to the dynamics while allowing a time step size two orders of magnitude larger than a resolved blob-link simulation. We conclude by applying our approach to a suspension of cross-linked semiflexible fibers (neglecting hydrodynamic interactions between fibers), where we study how semiflexible fluctuations affect bundling dynamics. We find that semiflexible filaments bundle faster than rigid filaments even when the persistence length is large, but show that semiflexible bending fluctuations only further accelerate agglomeration when the persistence length and fiber length are of the same order.


Developments in infertility therapy--diagnosis of genetic disease in embryos.
The general practitioner plays a vital role in assisting couples through the difficult and emotional field of assisted reproductive techniques including in vitro fertilisation (IVF). This article discusses the most recent developments in IVF so that GPs may better explain this ever changing field of medicine to their patients. This article begins by explaining how sperm can be brought together with oocytes for fertilisation outside the body, and then moves on to selecting the most genetically appropriate embryos for implantation. From this comes the issue of examining the fertilised oocytes to detect abnormalities, and the options available to couples with ethical concerns. The promise of regenerative medicine through the use of sperm cells is also discussed.


Construction of an expression system for engineering of the lantibiotic Pep5.
Pep5 is a lanthionine-containing antimicrobial peptide which is produced by Staphylococcus epidermidis 5. Its structural gene, pepA, is located on the 20-kb plasmid pED503. A 6.2-kb fragment of pED503 containing pepA, the immunity gene pepI, and 5.4 kb of downstream sequence was able to direct biosynthesis of biologically active Pep5 in a nonproducing variant of the producer strain which is devoid of pED503. In addition to producing wild-type Pep5 with a molecular mass of 3,488 Da, the clone produced a peptide with an eightfold-lower bactericidal activity and a mass of 3,506 Da, indicative of incomplete dehydration of one hydroxyamino acid. For construction of the expression system, this 6.2-kb fragment was cut into a 1.39-kb fragment containing pepA and pepI and a 4.8-kb fragment covering the remaining downstream region. This 4.8-kb fragment was directly cloned into an Escherichia coli-Staphylococcus shuttle vector, yielding a new plasmid (pGB9) into which mutated pepA genes generated on the 1.39-kb fragment can be reinserted to yield a functional Pep5 biosynthesis gene cluster. To test the expression system, two mutants were constructed. Lys-18-Pro Pep5 was produced in its dehydrated form and a partially hydrated form in amounts comparable to those of the wild-type peptide. In contrast, only small amounts of Phe-23-Asp Pep5 were excreted, indicating that some residues in the propeptide part of the prelantibiotic may be crucial for certain steps in the biosynthetic pathway of lantibiotics.


Interfacial synthesis: amphiphilic monomers assisted ultrarefining of mesoporous manganese oxide nanoparticles and the electrochemical implications.
Amphiphilic monomers, namely pyrrole and aniline, were used to reduce permanganate ion (MnO(4)(-)) at the dichloromethane/water interface for the preparation of ultrafine manganese oxide (MnO(x), x ≤ 2) nanoparticles (NPs). These monomers did not undergo polymerization upon oxidation by MnO(4)(-), but exerted an interesting effect of ultrarefining the produced MnO(x) NPs from reducing MnO(4)(-) at the organoaqueous interface. This was attributed to the ability of the monomer to access the interfacial reaction sites from both organic and aqueous phases, and hence retard the as-produced MnO(x) nuclei from aggregation at the interface. Such obtained products were mesoporous matrixes of three-dimensionally interconnected and uniform pseudospherical MnO(x) NPs (<20 nm). On the contrary, using a more hydrophobic monomer, i.e., o-aminophenol, to reduce MnO(4)(-) produced a composite of nanobelts of poly(o-aminophenol) embedded in micrometer-sized MnO(x) blocks. The ultrafine MnO(x) NPs prepared from using aniline or pyrrole exhibited highly capacitive behavior in aqueous Na(2)SO(4), promising their use in supercapacitors. It was also found that the MnO(x) NPs prepared from pyrrole-assisted synthesis possessed higher specific capacitance than that from aniline-assisted synthesis, despite the latter having a higher specific surface area. This difference is discussed in terms of crystallographic properties and water contents of these two samples.


The FMRFamide-like neuropeptide AF2 (Ascaris suum) is present in the free-living nematode, Panagrellus redivivus (Nematoda, Rhabditida).
Available primary structural information suggests that the FMRFamide-related peptides (FaRPs) from parasitic and free-living nematodes are different, and that free-living forms may not represent appropriate models for the study of the neurochemistry of parasitic forms in the laboratory. However, here we report the isolation and unequivocal identification of AF2 (originally isolated from the parasite, Ascaris suum) from acidified alcoholic extracts of the free-living species, Panagrellus redivivus. While reverse-phase HPLC analysis of extracts revealed FMRFamide-immunoreactivity to be highly heterogeneous, AF2 was the predominant FMRFamide-immunoreactive peptide present (at least 26 pmol/g wet weight of worms). This peptide was also the major immunoreactant identified by an antiserum raised to the conserved C-terminal hexapeptide amide of mammalian pancreatic polypeptide (PP), which has been used previously to isolate neuropeptide F (NPF). These observations were confirmed by radioimmunoassay and chromatographic fractionation of an acidified alcoholic extract of A. suum heads. The FMRFamide-related peptides present in a nematode extract may be highly dependent on the extraction medium employed, and these data would suggest that this complement of neuropeptides may not be as different between parasitic and free-living nematodes as initial studies have suggested. Finally, all of the evidence suggests that NPF is not present in nematodes and that the PP-immunoreactant previously demonstrated immunochemically is probably AF2.


Post-exposure sleep deprivation facilitates correctly timed interactions between glucocorticoid and adrenergic systems, which attenuate traumatic stress responses.
Reliable evidence supports the role of sleep in learning and memory processes. In rodents, sleep deprivation (SD) negatively affects consolidation of hippocampus-dependent memories. As memory is integral to post-traumatic stress symptoms, the effects of post-exposure SD on various aspect of the response to stress in a controlled, prospective animal model of post-traumatic stress disorder (PTSD) were evaluated. Rats were deprived of sleep for 6 h throughout the first resting phase after predator scent stress exposure. Behaviors in the elevated plus-maze and acoustic startle response tests were assessed 7 days later, and served for classification into behavioral response groups. Freezing response to a trauma reminder was assessed on day 8. Urine samples were collected daily for corticosterone levels, and heart rate (HR) was also measured. Finally, the impact of manipulating the hypothalamus-pituitary-adrenal axis and adrenergic activity before SD was assessed. Mifepristone (MIFE) and epinephrine (EPI) were administered systemically 10-min post-stress exposure and behavioral responses and response to trauma reminder were measured on days 7-8. Hippocampal expression of glucocorticoid receptors (GRs) and morphological assessment of arborization and dendritic spines were subsequently evaluated. Post-exposure SD effectively ameliorated long-term, stress-induced, PTSD-like behavioral disruptions, reduced trauma reminder freezing responses, and decreased hippocampal expression of GR compared with exposed-untreated controls. Although urine corticosterone levels were significantly elevated 1 h after SD and the HR was attenuated, antagonizing GRs with MIFE or stimulation of adrenergic activity with EPI effectively abolished the effect of SD. MIFE- and EPI-treated animals clearly demonstrated significantly lower total dendritic length, fewer branches and lower spine density along dentate gyrus dendrites with increased levels of GR expression 8 days after exposure, as compared with exposed-SD animals. Intentional prevention of sleep in the early aftermath of stress exposure may well be beneficial in attenuating traumatic stress-related sequelae. Post-exposure SD may disrupt the consolidation of aversive or fearful memories by facilitating correctly timed interactions between glucocorticoid and adrenergic systems.


Fast network centrality analysis using GPUs.
With the exploding volume of data generated by continuously evolving high-throughput technologies, biological network analysis problems are growing larger in scale and craving for more computational power. General Purpose computation on Graphics Processing Units (GPGPU) provides a cost-effective technology for the study of large-scale biological networks. Designing algorithms that maximize data parallelism is the key in leveraging the power of GPUs. We proposed an efficient data parallel formulation of the All-Pairs Shortest Path problem, which is the key component for shortest path-based centrality computation. A betweenness centrality algorithm built upon this formulation was developed and benchmarked against the most recent GPU-based algorithm. Speedup between 11 to 19% was observed in various simulated scale-free networks. We further designed three algorithms based on this core component to compute closeness centrality, eccentricity centrality and stress centrality. To make all these algorithms available to the research community, we developed a software package gpu-fan (GPU-based Fast Analysis of Networks) for CUDA enabled GPUs. Speedup of 10-50× compared with CPU implementations was observed for simulated scale-free networks and real world biological networks. gpu-fan provides a significant performance improvement for centrality computation in large-scale networks. Source code is available under the GNU Public License (GPL) at http://bioinfo.vanderbilt.edu/gpu-fan/.


Risk Factors for Surgical Site Infection after Operative Fixation of Acetabular Fractures: Is Psoas Density a Useful Metric?
Surgical site infection (SSI) occurs in 5% to 7% of patients undergoing operative fixation of acetabular fractures, with reported risk factors including longer operative duration, increased blood loss, pelvic artery embolization, and concurrent abdominal organ injury, among others. Psoas muscle density is a measure of muscle quality and, as a metric for sarcopenia and/or nutrition status, has been associated with poor outcomes such as mortality across multiple surgical specialties. To date, psoas muscle density has not been explored for its associations with SSI in acetabular fracture patients.Questions/purposes (1) Is decreased psoas muscle density, as measured by Hounsfield units, associated with an increased SSI risk after acetabular fracture fixation? (2) What patient, operative, and hospital variables are associated with an increased SSI risk after acetabular fracture fixation? Between 2012 to 2017, surgeons performed 684 acetabular ORIF procedures at one level I trauma center. Of those, 8% (56 of 684) did not meet inclusion criteria, leaving 92% (n = 628) for analysis in this study. The median (range) follow-up duration was 12 months (0.5-77). Patient demographics, comorbidities, operative and in-hospital variables, and psoas muscle density measured using preoperative pelvic CT images-acquired for all operative acetabular fracture patients-were analyzed. SSI was defined by positive culture results obtained during irrigation and débridement. Overall, 7% (42 of 628) of patients had an SSI. A multivariable regression analysis was performed to identify independent risk factors. Sensitivity analysis was performed with minimum follow-up set at 3 months and 6 months. There was no difference in the mean psoas muscle density between patients with SSI (50.9 ± 10.2 Hounsfield units [HUs]) and those who did not have an SSI within 1 year of open reduction and internal fixation (51.4 ± 8.1 HUs) (mean difference: 0.5 [95% confidence interval -2.34 to 3.32]; p = 0.69). Four variables were independently associated with an increased risk of SSI: increased operative time (1.04 [95% CI 1.00 to 1.07]; p = 0.03), estimated blood loss (1.08 [95% CI 1.02 to 1.14]; p = 0.01), female sex (2.34 [95% CI 1.19 to 4.60]; p = 0.01), and intravenous drug use (3.95 [95% CI 1.51 to 10.33]; p = 0.01). Sensitivity analysis showed no change in results using either 3-month or 6-month minimum follow-up. Risk factors for SSI after acetabular fixation include female sex, intravenous drug use, prolonged operative times, and increased intraoperative blood loss. Although the density of the psoas muscle may be a surrogate for nutritional markers, it was not associated with SSI in our patients with acetabular fractures. Thus, it is not useful for risk assessment of SSI in the general population with acetabular fracture; however, future studies with larger sample sizes of patients older than 60 years may re-investigate this marker for SSI risk. Contrary to the results of previous studies, pelvic artery embolization, intraoperative blood transfusion, and intensive care unit stay did not increase the risk of SSI; however, we may have been underpowered to detect differences in these secondary endpoints. Future large, multisite studies may be needed to address these conflicting results more definitively. Level III, therapeutic study.


Compartmental distribution of tumor-specific monoclonal antibodies in human melanoma xenografts.
Monoclonal antibodies (MAb) are attractive for tumor therapy because of their exquisite specificity. Although a majority of tumor cells in small (< or = 20 mg) solid tumors can be labeled following systemic administration of antitumor cell MAbs, little quantitative information is available as to the distribution of these MAbs within the several compartments that comprise solid tumors. Our goal was to provide such data in a well-characterized melanoma xenograft system. In accord with earlier work, i.v.-injected, melanoma-specific MAbs 436 and IND1, directed, respectively, against the 125 kD and HMW-melanoma-associated antigens, accumulated in M21 and SK-MEL-2 tumor xenografts in amounts of approximately 20% of injected dose/g. However, only 20-24% of the MAbs present in tumor xenografts was bound to tumor cells; the great majority (76-80%) was in the tumor extracellular fluid (ECF) and collagenous residue fractions. These results could not be accounted for by MAb degradation or release of MAbs from tumor cells during xenograft dissociation. Rather, they reflected in large part interactions of MAbs with antigens which tumors had shed into the ECF. Thus, 48 h after i.v. injection of 20 micrograms of melanoma-specific, biotin-tagged MAb, 46-66% of that present in the tumor ECF was complexed with melanoma-associated antigens. Overall, 61-73% of the MAbs recovered from tumor xenografts were bound to tumor antigens (either to tumor cells themselves or to tumor-shed antigens). In contrast, only approximately 4% of a melanoma-nonspecific MAb (B72.3) accumulated per g tumor after i.v. injection and nearly all of this was free in the ECF. Consistent with these data, fluorescence microscopy revealed that i.v.-injected, fluorescein-tagged MAbs achieved highest concentrations in tumor stroma, particularly at the tumor-host interface. Flow cytometry of dissociated solid tumors revealed that both the fraction of MAb-labeled tumor cells and the amount of MAb/tumor cell could be increased by increasing the administered i.v. dose of melanoma-specific MAb. Nonetheless, even at the highest i.v. injected dose (300 micrograms), 15-37% of tumor cells lacked detectable MAb labeling. Taken together, the data indicate that delivery of tumor cell-specific MAbs to solid tumors cannot be equated with their delivery to tumor cells. This distinction is important for immunotherapeutic approaches that require MAb contact with tumor cells.


Susceptibility to asthma and eczema from mucosal and epidermal expression of distinctive genes.
The past several years have seen an increase in the rate at which genes that are associated with allergic asthma and eczema are discovered. This review -examines genetic association, gene expression, and functional studies that have identified genes that are expressed in the epithelial cells of the skin and lung and are involved in the pathogenesis of allergic asthma and eczema. This includes the genes encoding thymic stromal lympho-poietin (TSLP) and suppressor of cytokine signaling (SOCS3) that are involved in the activation of T-helper 2 cells, the microbial pattern recognition receptors nucleotide-binding oligomerization domain (NOD) genes (CARD4 and CARD15), Toll-like receptors (TLR2 and TLR4), and filaggrin, a protein required for effective barrier defense of the skin. Therefore, the development of allergic disease involves both the adaptive and innate immune systems, and the expression of these genes in the skin and lungs suggests a link to environmental -triggers at body surfaces.


Interpreting the pervasive observation of U-shaped Site Frequency Spectra.
The standard neutral model of molecular evolution has traditionally been used as the null model for population genomics. We gathered a collection of 45 genome-wide site frequency spectra from a diverse set of species, most of which display an excess of low and high frequency variants compared to the expectation of the standard neutral model, resulting in U-shaped spectra. We show that multiple merger coalescent models often provide a better fit to these observations than the standard Kingman coalescent. Hence, in many circumstances these under-utilized models may serve as the more appropriate reference for genomic analyses. We further discuss the underlying evolutionary processes that may result in the widespread U-shape of frequency spectra.


Has widespread use of biologic and immunosuppressant therapy for ulcerative colitis affected surgical trends? Results of a questionnaire survey of surgical institutions in Japan.
The aim of the study is to assess the relationship between the introduction of biologic and immunosuppressant therapy and the number of patients undergoing surgery for ulcerative colitis (UC). A questionnaire survey about patients undergoing surgery for UC was sent to 26 teaching hospitals throughout Japan. The questionnaire period spanned from 2008 to 2013, to account for the introduction of tacrolimus (2009) and infliximab (2010). The total number of patients who underwent surgery was 297, 291, 273, 255, 300, and 305 in 2008, 2009, 2010, 2011 2012, and 2013, respectively. The emergency surgery rate remained stable at 32-34 % each year. The proportion of patients who underwent surgery for cancer increased from 13.8 % in 2008 to 20 % in 2013. In 2013, 41, 38, and 6 % of patients who underwent surgery had received treatment with a biologic, tacrolimus, and cyclosporine, respectively. No institution reported an increase in postoperative complications among patients treated with immunosuppressive drugs. The number of patients undergoing surgery decreased temporarily soon after infliximab and tacrolimus first became widely available, but subsequently increased again. The emergency surgery rate remained unchanged throughout the study period. These data show that immunosuppressive drugs have had little effect on the risk of postoperative complications.


Macrovascular complication phenotypes in type 2 diabetic patients.
Macrovascular diseases (MVD) in type 2 diabetes mellitus (T2DM) are often considered all together, without discriminating the areas involved. The aim of our study was to analyse MVD prevalence in a large population of T2DM patients by dividing the cases into subgroups according to MVD sites (NMVD, no MVD; NSCS, non-significant carotid stenosis; CBVD, cerebrovascular disease; CAD, coronary artery disease; PAD, peripheral artery disease; PVD, polyvascular disease) and studying the anthropometric, clinical and laboratory parameters in each group. A diabetic outpatient cohort (n = 1199) was retrospectively studied. Demographic, clinical and laboratory parameters were included in analyses. A thorough cardiovascular history as documented by previous medical records (including medical and hospital records) and vascular laboratory studies (including standardised electrocardiogram, echocardiogram, provocative tests for cardiac ischaemia, ankle/brachial index, duplex ultrasonography of the carotid and lower limbs and, in selected cases, computed tomography angiography, carotid and peripheral arteriography and evaluation of transcutaneous oxygen pressure), was collected for all of the patients. Standardised procedures were used to assess microvascular complications as well as metabolic syndrome (Mets). The unadjusted MVD prevalence was 46.4% among the participants. The majority of patients with MVD were in the PVD group. In the multivariate analysis, age, male sex and diabetes duration were independent risk factors for PAD and PVD (P < 0.01). A low HDL-C value was an independent risk factor in the CAD and PVD groups (P = 0.03). Very high frequencies of MetS were observed in the PAD and PVD groups (94.9 and 95.7% respectively). The most MetS diagnostic criteria were recorded among members of the CAD group (all or all-1 criteria were present in 73% of patients). The average age in the CAD group (64.5 y) was comparable to that of the NMVD group. Microvascular complications were more frequent in the PAD and PVD patients. Phenotypic heterogeneity is associated with different macrovascular complications in T2DM patients. These findings might have clinical implications for developing diagnostic and therapeutic strategies targeting type 2 diabetes.


Differences in LexA regulon structure among Proteobacteria through in vivo assisted comparative genomics.
The LexA regulon encompasses an ensemble of genes involved in preserving cell viability under massive DNA damage and is present in most bacterial phyla. Up to date, however, the scope of this network had only been assessed in the Gamma Proteobacteria. Here, we report the structure of the LexA regulon in the Alpha Proteobacteria, using a combined approach that makes use of in vitro and in vivo techniques to assist and validate the comparative genomics in silico methodology. This leads to the first experimentally validated description of the LexA regulon in the Alpha Proteobacteria, and comparison of regulon core structures in both classes suggests that a least common multiple set of genes (recA, ssb, uvrA and ruvCAB) might be a defining property of the Proteobacteria LexA network.


Air conduction, bone conduction, and soft tissue conduction audiograms in normal hearing and simulated hearing losses.
In order to differentiate between a conductive hearing loss (CHL) and a sensorineural hearing loss (SNHL) in the hearing-impaired individual, we compared thresholds to air conduction (AC) and bone conduction (BC) auditory stimulation. The presence of a gap between these thresholds (an air-bone gap) is taken as a sign of a CHL, whereas similar threshold elevations reflect an SNHL. This is based on the assumption that BC stimulation directly excites the inner ear, bypassing the middle ear. However, several of the classic mechanisms of BC stimulation such as ossicular chain inertia and the occlusion effect involve middle ear structures. An additional mode of auditory stimulation, called soft tissue conduction (STC; also called nonosseous BC) has been demonstrated, in which the clinical bone vibrator elicits hearing when it is applied to soft tissue sites on the head, neck, and thorax. The purpose of this study was to assess the relative contributions of threshold determinations to stimulation by STC, in addition to AC and osseous BC, to the differential diagnosis between a CHL and an SNHL. Baseline auditory thresholds were determined in normal participants to AC (supra-aural earphones), BC (B71 bone vibrator at the mastoid, with 5 N application force), and STC (B71 bone vibrator) to the submental area and to the submandibular triangle with 5 N application force) stimulation in response to 0.5, 1.0, 2.0, and 4.0 kHz tones. A CHL was then simulated in the participants by means of an ear plug. Separately, an SNHL was simulated in these participants with 30 dB effective masking. STUDY SAMPLE consisted of 10 normal-hearing participants (4 males; 6 females, aged 20-30 yr). AC, BC, and STC thresholds were determined in the initial normal state and in the presence of each of the simulations. The earplug-induced CHL simulation led to a mean AC threshold elevation of 21-37 dB (depending on frequency), but not of BC and STC thresholds. The masking-induced SNHL led to a mean elevation of AC, BC, and STC thresholds (23-36 dB, depending on frequency). In each type of simulation, the BC threshold shift was similar to that of the STC threshold shift. These results, which show a similar threshold shift for STC and for BC as a result of these simulations, together with additional clinical and laboratory findings, provide evidence that BC thresholds likely represent the threshold of the nonosseous BC (STC) component of multicomponent BC at the BC stimulation site, and thereby succeed in clinical practice to contribute to the differential diagnosis. This also provides evidence that STC (nonosseous BC) stimulation at low intensities probably does not involve components of the middle ear, represents true cochlear function, and therefore can also contribute to a differential diagnosis (e.g., in situations where the clinical bone vibrator cannot be applied to the mastoid or forehead with a 5 N force, such as in severe skull fracture).


[Characteristics of microcirculation in patients with diabetic angiopathies].
The radionuclide technique was used to study regional microcirculation in 139 patients with diabetic angiopathies of the lower limbs. All the examined demonstrated impairment of the muscular bloodflow, that increased depending on the disease stage and diabetes mellitus standing. No differences were recorded in the degree of bloodflow impairment in the muscles of patients treated with sulfanilurea drugs and insulin. Comparison of the degree of changes in the muscular bloodflow in diabetic angiopathies of the lower limbs and atherosclerosis obliterans of lower limb vessels in subjects without diabetes mellitus demonstrated that microcirculation in the former group patients was affected to a greater measure. It is desirable that the complex of therapeutic measures should include drugs that improve microcirculation at the early stages of the management of patients with diabetic angiopathies of the lower limbs.


Willingness to pay for cataract surgery in rural Southern China.
To study willingness to pay for cataract surgery, and its associations, in Southern China. Cross-sectional willingness-to-pay interview incorporating elements of the open-ended and bidding formats. Three-hundred thirty-nine persons presenting for cataract screening in Yangjiang, China, with presenting visual acuity (VA) < or = 6/60 in either eye due to cataract. Subjects underwent measurement of their VA and a willingness-to-pay interview. Age, gender, literacy, education, and annual income also were recorded. Maximum amount that the subjects would be willing to pay for cataract surgery. Among 325 (95.9%) subjects completing the interview, 169 (52.0%) were 70 years or older, 213 (65.5%) were women, and 217 (66.8%) had an annual income of <5000 renminbi (5000 = US 625 dollars). Eighty percent (n = 257) of participants were willing to pay something for surgery (mean, 442+/-444 renminbi [US 55 dollars+/-55]). In regression models, older subjects were willing to pay less (8 renminbi [US 1 dollar] per year of age; P = 0.01). Blind subjects were significantly more likely (odds ratio, 5.7; 95% confidence interval, 1.7-19.3) to pay anything for surgery, but would pay on average 255 renminbi (US 32 dollars) less (P = 0.004). Persons at the highest annual income level (>10,000 renminbi [US 1250 dollars]) would pay 50 dollars more for surgery than those at the lowest level (<5000 renminbi) (P = 0.0003). The current cost of surgery in this program is 500 renminbi (US 63 dollars). Sustainable programs will need to attract younger, more well-to-do persons with better vision, while still providing access to the neediest patients.


Human spongiform encephalopathies in marmoset monkeys (Saguinus sp.).
Brain homogenates (10% w/v) from five of seven kuru patients inoculated intracerebrally (i.c., 0.1 ml) into marmosets (Saguinus sp.) induced a rapidly progressive CNS disease 26, 31, 36, 76 and 94 months postinoculation. Serial marmoset passages of kuru were accomplished by i.c. inoculation of neonatal marmosets with brain homogenates from marmosets with experimentally induced kuru. The incubation periods ranged from 1.5 to 11 months (average 7.3) in 19 animals, 20-25 months in four animals and greater than 26 months in two animals. Symptoms and brain lesions of the induced disease were compatible with kuru as observed in humans and other nonhuman primates. Creutzfeldt-Jakob disease (CJD) has been induced by i.c. inoculation of marmosets with brain homogenates from two of four human CJD patients with incubation periods of 43 and 54 months and is in serial passage.


Aminoglycosides: a practical review.
Aminoglycosides are potent bactericidal antibiotics that act by creating fissures in the outer membrane of the bacterial cell. They are particularly active against aerobic, gram-negative bacteria and act synergistically against certain gram-positive organisms. Gentamicin is the most commonly used aminoglycoside, but amikacin may be particularly effective against resistant organisms. Aminoglycosides are used in the treatment of severe infections of the abdomen and urinary tract, as well as bacteremia and endocarditis. They are also used for prophylaxis, especially against endocarditis. Resistance is rare but increasing in frequency. Avoiding prolonged use, volume depletion and concomitant administration of other potentially nephrotoxic agents decreases the risk of toxicity. Single daily dosing of aminoglycosides is possible because of their rapid concentration-dependent killing and post-antibiotic effect and has the potential for decreased toxicity. Single daily dosing of aminoglycosides appears to be safe, efficacious and cost effective. In certain clinical situations, such as patients with endocarditis or pediatric patients, traditional multiple dosing is still usually recommended.


A study on the sentiments and psychology of twitter users during COVID-19 lockdown period.
The outbreak of the novel Coronavirus in late 2019 brought severe devastation to the world. The pandemic spread across the globe, infecting more than ten million people and disrupting several businesses. Although social distancing and the use of protective masks were suggested all over the world, the cases seem to rise, which led to worldwide lockdown in different phases. The rampant escalation in the number of cases, the global effects, and the lockdown may have a severe effect on the psychology of people. The emergency protocols implemented by the authorities also lead to increased use in the number of multimedia devices. Excessive use of such devices may also contribute to psychological disorders. Hence, hence it is necessary to analyze the state of mind of people during the lockdown. In this paper, we perform a sentiment analysis of Twitter data during the pandemic lockdown, i.e., two weeks and four weeks after the lockdown was imposed. Investigating the sentiments of people in the form of positive, negative, and neutral tweets would assist us in determining how people are dealing with the pandemic and its effects on a psychological level. Our study shows that the lockdown witnessed more number positive tweets globally on multiple datasets. This is indicative of the positivity and optimism based on the sentiments and psychology of Twitter users worldwide. The study will be effective in determining people's mental well-being and will also be useful in devising appropriate lockdown strategies and crisis management in the future.


Recombinant domain III of perlecan promotes cell attachment through its RGDS sequence.
Perlecan has been previously been shown to support attachment of a wide variety of cells through interactions of its core protein with the cell surface. The core protein domains involved in cell adhesion are, however, unknown. The laminin-like domain III of murine perlecan contains an RGDS sequence and is a likely candidate for supporting integrin-mediated cell attachment. We made a cDNA construct corresponding to domain III and containing an in frame signal peptide at the 5' end as well as in frame a stop codon at the 3' end by using cDNA clones to perlecan. The construct was inserted into the pRC/CMV vector and transfected into HT1080 cells, and the secreted recombinant domain III, a 130-kDa protein, was purified from the medium. The size of proteolytic fragments produced by digestion with V8 protease as well as analysis of the rotary shadowed image of the recombinant protein indicated it was produced in a native conformation. Recombinant domain III coated on tissue culture dishes, supports adhesion of an epithelial-like mouse mammary tumor cell line MMT 060562 in a dose-dependent manner. This interaction was inhibited specifically by the RGDS synthetic peptide and intact perlecan, but not laminin. This domain III RGD-dependent cell attachment activity indicates a role for perlecan in integrin-mediated signaling.


Diagnostic studies in clinical practice.
In conclusion, it has become obvious that the diagnostic approach to the patient with low back pain is multidisciplinary in nature. The diagnostic and treatment modalities available to the spine surgeon in 1983 have been expanded greatly. No longer does the frustration of dealing with a nebulous realm of pain complaints involving the low back have be tolerated. Specific diagnoses can be made and treatment instituted. New, less invasive diagnostic techniques continue to evolve, including such things as nuclear magnetic resonance. In addition, the importance of diet, physical exercise, relaxation, and overall fitness has become generally accepted in the United States today. It has also become much easier to gain the patient's cooperation in regard to his or her responsibility in the treatment program.


What's New in the Orthopaedic Treatment of Ambulatory Children With Cerebral Palsy Using Gait Analysis.
Limb deformities in ambulatory children with cerebral palsy (CP) are common. The natural history of lower extremity deformities is variable and the impact on gait is managed with many treatment modalities. Effective interventions must consider the underlying pathophysiology, patient-specific goals, and incorporate objective outcome assessment. Evaluation and treatment include observation, tone management multilevel orthopaedic surgery to address muscle contractures and bony deformities, and the use of gait analysis for preoperative and postoperative assessment. A PubMed search of the orthopaedic literature for studies published between January 2016 and February 2019 was performed. Eligible abstracts included the use of 3-dimensional instrumented gait analysis in the evaluation and treatment of the lower extremities in ambulatory children with CP. Seven hundred twenty abstracts were reviewed, with 84 papers identified as eligible, of which 45 full manuscripts were included for detailed review. The review summarized recent advances regarding the treatment of torsional alignment, knee deformities and clinical gait evaluation with visual assessment tools compared with instrumented gait analysis. Gait analysis of ambulatory children with CP remains essential to evaluation and surgical decision-making. Promising results have been reported with the goal of maintaining or reaching a higher level of function and increased endurance. Level IV-literature review.


A BAC based physical map and genome survey of the rice false smut fungus Villosiclava virens.
Rice false smut caused by Villosiclava virens is a devastating fungal disease that spreads in major rice-growing regions throughout the world. However, the genomic information for this fungal pathogen is limited and the pathogenic mechanism of this disease is still not clear. To facilitate genetic, molecular and genomic studies of this fungal pathogen, we constructed the first BAC-based physical map and performed the first genome survey for this species. High molecular weight genomic DNA was isolated from young mycelia of the Villosiclava virens strain UV-8b and a high-quality, large-insert and deep-coverage Bacterial Artificial Chromosome (BAC) library was constructed with the restriction enzyme HindIII. The BAC library consisted of 5,760 clones, which covers 22.7-fold of the UV-8b genome, with an average insert size of 140 kb and an empty clone rate of lower than 1%. BAC fingerprinting generated successful fingerprints for 2,290 BAC clones. Using the fingerprints, a whole genome-wide BAC physical map was constructed that contained 194 contigs (2,035 clones) spanning 51.2 Mb in physical length. Bidirectional-end sequencing of 4,512 BAC clones generated 6,560 high quality BAC end sequences (BESs), with a total length of 3,030,658 bp, representing 8.54% of the genome sequence. Analysis of the BESs revealed general genome information, including 51.52% GC content, 22.51% repetitive sequences, 376.12/Mb simple sequence repeat (SSR) density and approximately 36.01% coding regions. Sequence comparisons to other available fungal genome sequences through BESs showed high similarities to Metarhizium anisopliae, Trichoderma reesei, Nectria haematococca and Cordyceps militaris, which were generally in agreement with the 18S rRNA gene analysis results. This study provides the first BAC-based physical map and genome information for the important rice fungal pathogen Villosiclava virens. The BAC clones, physical map and genome information will serve as fundamental resources to accelerate the genetic, molecular and genomic studies of this pathogen, including positional cloning, comparative genomic analysis and whole genome sequencing. The BAC library and physical map have been opened to researchers as public genomic resources (http://gresource.hzau.edu.cn/resource/resource.html).


Nonlinear myofilament regulatory processes affect frequency-dependent muscle fiber stiffness.
To investigate the role of nonlinear myofilament regulatory processes in sarcomeric mechanodynamics, a model of myofilament kinetic processes, including thin filament on-off kinetics and crossbridge cycling kinetics with interactions within and between kinetic processes, was built to predict sarcomeric stiffness dynamics. Linear decomposition of this highly nonlinear model resulted in the identification of distinct contributions by kinetics of recruitment and by kinetics of distortion to the complex stiffness of the sarcomere. Further, it was established that nonlinear kinetic processes, such as those associated with cooperative neighbor interactions or length-dependent crossbridge attachment, contributed unique features to the stiffness spectrum through their effect on recruitment. Myofilament model-derived sarcomeric stiffness reproduces experimentally measured sarcomeric stiffness with remarkable fidelity. Consequently, characteristic features of the experimentally determined stiffness spectrum become interpretable in terms of the underlying contractile mechanisms that are responsible for specific dynamic behaviors.


[Evoked oto-acoustic emissions (EOE) as screening method in infants].
The authors consider the problems of the early diagnosis of paediatric hypoacusis, presenting a study done on twenty audiological high risk children that were subjected to audiometric screening by delayed cochlear otoacoustic emissions (EOE) and brainstem auditory evoked potentials (BEAPs). Eighteen of twenty children that were examined were normal, while two had bilateral sensorineural hearing loss. EOE were evoked in all patients that presented normal BAEP thresholds, while they were absent in deaf subjects. Evoked otoacoustic emissions research allows us to identify two groups of subjects: those with normal EOE who can be considered normal hearing subjects, and those without EOE who may present a disturbed auditory system. Nevertheless, EOE testing does not allow us to judge the type of hearing loss. The time for EOE testing is approximately five minutes for each subject. On the grounds of their experience, the authors conclude that EOE testing represents a useful and reliable test which differentiates normal auditory function subjects from hypoacoustic ones. Compared to other techniques used in audiological paediatric diagnosis, such as reactometry, BOEL test and Crib. O. Gram, which present the possibility of false positive and false negative results, and BSERA, which even if reliable, must be limited to few selected audiological high-risk subjects, EOE is easy to implement and readily available. Major limitations of this technique seem to be the possibility of false positives, and the impossibility to specify localisation and type of the hearing loss by EOE only.


Astrocytoma in a dog causing convulsions.
An adult, male, 7 Kg. dog was presented because of a convulsion. This progressed and interictal signs became apparent. A slight left spastic hemiparesis was present with a normal gait and posture. A partial left visual deficit with intact pupillary reflexes became evident. All signs were referable to a right cerebral lesion. Necropsy revealed an astrocytoma in the right cerebrum compressing the internal capsule and optic tract.


The 2005 USDA Food Guide Pyramid is associated with more adequate nutrient intakes within energy constraints than the 1992 Pyramid.
The USDA issued the Food Guide Pyramid (FGP) to help Americans choose healthy diets. We examined whether adherence to the 1992 and 2005 FGP was associated with moderate energy and adequate nutrient intakes. We used data for 2138 men and 2213 women > 18 y old, from the 2001-2002 U.S. National Health and Nutrition Examination Survey (NHANES). Quadratic programming was used to generate diets with minimal departure from intakes reported for the NHANES 2001-02. We examined the effect of the number of servings/d of Food Pyramid groups set at 1992 and at 2005 FGP recommendations for 1600, 2200, and 2800 kcal (1 kcal = 4.184 kJ) levels. We calculated energy and nutrients provided by different FGP dietary patterns. Within current U.S. dietary practices, following the 1992 FGP without sodium restriction may provide 200 more kcal than recommended for each energy level. Although it can meet most of old nutrient recommendations (1989), it fails to meet the latest dietary reference intakes, especially for the 1600 kcal level. The 2005 FGP appears to provide less energy and more adequate nutrient intakes, with the exception of vitamin E and potassium for some groups. However, without discretionary energy restriction, Americans are at risk of having excessive energy intake even if they follow the 2005 FGP food serving recommendations. Our analysis suggests that following the 2005 FGP may be associated with lower energy and optimal nutrient intake. Careful restriction of discretionary calories appears necessary for appropriate energy intakes to be maintained.


Feulgen microdensitometry and analysis of S-phase cells in cervical tumour biopsies.
Tissue specimens from the cervical tumours of 70 patients undergoing radiotherapy were examined by Feulgen microdensitometry. Twenty-five of the 70 specimens were also subjected to in-vitro tritiated thymidine autoradiography to determine the proportion of DNA synthesising cells they contained. A spectrum of frequency distributions of nuclear DNA content was obtained from Feulgen microdensitometry, but by inspecting the data the basic DNA content of malignant cells could be established in most cases. Fifty-nine per cent of the tumours were 'diploid', 10% 'tetraploid', 13% 'diploid to tetraploid', and the remaining 18% 'aneuploid'. Grafical analysis of DNA frequencies from 48 'diploid' or 'tetraploid' tumours enabled the proportion of DNA synthesising (S) cells to be estimated by frequency distribution analysis. Estimates of the S component ranged from nil to 30%, were log normally distributed, and comparable to direct measurements of cells in S determined by autoradiography for 25 cases (range 1.2-28.7%). For all paired data the mean difference was 1.2 +/- 1.45% (confidence limits), suggesting that overall Feulgen microdensitometry analysis may be an equally valid technique in providing cellular kinetic information with human tumour material.


Differential control of ventilation among inbred strains of mice.
The role genetic factors play in ventilatory control was examined by challenging eight inbred strains of mice to acute hypercapnia under normoxic and hypoxic conditions. Age-matched mice were exposed for 3-5 min to inspired gases of the following composition (FICO2:FIO2) 0.03:0.10, 2) 0.03:0.21, 3) 0.08:0.10, and 4) 0.08:0.21, with intermittent room air exposures. Breathing frequency (f) and tidal volume (VT) of unanesthetized, unrestrained mice were assessed by whole body plethysmography. During room air breathing, significant (P < 0.01) interstrain differences were noted in the pattern, but minute ventilation (VE) did not differ among the strains. Relative to room air, mild hypercapnia with hypoxia (0.03:0.10) significantly (P < 0.01) elevated VE in each strain, and the percent increase in VE of the DBA/2J strain was significantly (P < 0.05) greater than the other strains. The ventilatory response to these conditions was achieved primarily by a significant (P < 0.01) increase in f among the strains. During severely hypercapnic normoxia (0.08:0.21) and hypoxia (0.08:0.10), the increase in VE was significantly (P < 0.01) greatest in the C57BL/6J (B6) mice and least in the C3H/HeJ (C3) mice. The difference in hypercapnic VE between B6 and C3 strains was largely due to a significantly (P < 0.01) greater increase in VT by B6 mice. On the assumption that environmental factors were identical, these data suggest that genetic determinants govern interstrain variation in the magnitude and pattern of breathing during hypoxia and hypercapnia. Moreover, hypoxic and hypercapnic ventilatory responses appear to be influenced by different genetic mechanisms.


Characteristics of monolayer formation in vitro by the chytrid Batrachochytrium dendrobatidis.
Batrachochytrium dendrobatidis is a globally distributed generalist pathogen that has driven many amphibian populations to extinction. The life cycle of B. dendrobatidis has two main cell types, motile zoospores, and sessile reproductive sporangia. When grown in a nutrient-rich liquid medium, B. dendrobatidis forms aggregates of sporangia that transition into monolayers on surfaces and at the air-liquid interface. Pathogenic microorganisms use biofilms as mechanisms of group interactions to survive under harsh conditions in the absence of a suitable host. We used fluorescent and electron microscopy, crystal violet, transcriptomic, and gas chromatographic analyses to understand the characteristics of B. dendrobatidis monolayers. The cell-free monolayer fraction showed the presence of extracellular ribose, mannose, xylose, galactose, and glucose. Transcriptome analysis showed that 27%, 26%, and 4% of the genes were differentially expressed between sporangia/zoospores, monolayer/zoospores, and sporangia/monolayer pairs respectively. In pond water studies, zoospores developed into sporangia and formed floating aggregates at the air-water interface and attached film on the bottom of growth flasks. We propose that B. dendrobatidis can form surface-attached monolayers in nutrient-rich environments and aggregates of sporangia in nutrient-poor aquatic systems. These monolayers and aggregates may facilitate dispersal and survival of the fungus in the absence of a host. We provide evidence for using a combination of plant-based chemicals, allicin, gingerol, and curcumin as potential anti-chytrid drugs to mitigate chytridiomycosis.


Digital spatially incoherent Fresnel holography.
We present a new method for recording digital holograms under incoherent illumination. Light is reflected from a 3D object, propagates through a diffractive optical element (DOE), and is recorded by a digital camera. Three holograms are recorded sequentially, each for a different phase factor of the DOE. The three holograms are superposed in the computer, such that the result is a complex-valued Fresnel hologram. When this hologram is reconstructed in the computer, the 3D properties of the object are revealed.


Renin release and gene expression in intact rat kidney microvessels and single cells.
To investigate whether newborn kidney microvessels and isolated single microvascular cells have the capacity to release renin and/or alter the expression of the renin gene in response to adenylate cyclase stimulation, newborn kidney microvessels were isolated and purified (95%) using an iron perfusion/enzymatic digestion technique. Incubation of microvessels with either vehicle (control; C) or 10(-5) M forskolin (F) in media resulted in an increase in microvessel cAMP (0.67 +/- 0.13 vs. 22 +/- 4.6 pmol/min per mg protein) (P less than 0.005) and renin released into the culture media (1,026 +/- 98 vs. 1,552 +/- 159 pg angiotensin I/h per mg protein) (P = 0.008) (C vs. F). Renin mRNA levels in the newborn kidney microvessels increased 1.6-fold with forskolin treatment. Renin release by isolated, single microvascular cells (with or without forskolin) was assessed using the reverse hemolytic plaque assay. Forskolin administration resulted in an increase in the number of renin-secreting cells without changes in the amount of renin secreted by individual cells. In conclusion, newborn kidney microvessels and isolated renin-releasing microvascular cells possess a functionally active adenylate cyclase whose short-term stimulation results in accumulation of cAMP, a significant increase in renin release, and an enhancement of renin gene expression. The increase in renin release is due to recruitment of microvascular cells secreting renin. Recruitment of hormone-secreting cells in response to stimuli may prove to be a mechanism of general biological importance shared by many endocrine cell types.


Role of the striatum and the cerebellum in motor skill acquisition.
Motor skill acquisition was investigated in patients with Parkinson's disease (PD) or cerebellar dysfunction using two sensory-guided tracking tasks. The subjects had to learn to track a visual target (a square) on a computer screen by moving a joystick under two different conditions. In the unreversed task, the horizontal target movements were semi-predictable and could be anticipated. In the reversed task, the horizontal movements of a pointer which had to be kept within the target square were mirror-reversed to the joystick movements. PD patients showed intact learning of the semi-predictable task and reduced learning of the mirror-reversed task; patients with cerebellar dysfunction showed the opposite pattern. These findings are discussed in relation to the differential contribution of the cerebellum and the striatum to motor skill acquisition: the cerebellum appears to participate in the implementation of anticipatory movements, whereas the striatum may be critically involved in types of motor learning which require a high degree of internal elaboration.


Isolation of Nicotiana plumbaginifolia cDNAs encoding isoforms of serine acetyltransferase and O-acetylserine (thiol) lyase in a yeast two-hybrid system with Escherichia coli cysE and cysK genes as baits.
We applied the yeast two-hybrid system for screening of a cDNA library of Nicotiana plumbaginifolia for clones encoding plant proteins interacting with two proteins of Escherichia coli: serine acetyltransferase (SAT, the product of cysE gene) and O-acetylserine (thiol)lyase A, also termed cysteine synthase (OASTL-A, the product of cysK gene). Two plant cDNA clones were identified when using the cysE gene as a bait. These clones encode a probable cytosolic isoform of OASTL and an organellar isoform of SAT, respectively, as indicated by evolutionary trees. The second clone, encoding SAT, was identified independently also as a "prey" when using cysK as a bait. Our results reveal the possibility of applying the two-hybrid system for cloning of plant cDNAs encoding enzymes of the cysteine synthase complex in the two-hybrid system. Additionally, using genome walking sequences located upstream of the sat1 cDNA were identified. Subsequently, in silico analyses were performed aiming towards identification of the potential signal peptide and possible location of the deduced mature protein encoded by sat1.


The detection of canine autoantibodies to thyroid antigens by enzyme-linked immunosorbent assay, hemagglutination and indirect immunofluorescence.
Autoantibodies to thyroid antigens in serums from 34 clinically hypothyroid dogs were detected by various methods. Antibodies to thyroglobulin were detectable by enzyme-linked immunosorbent assay (ELISA) in 59%, by chromic chloride hemagglutination in 53% and by indirect immunofluorescence on formalin-fixed, paraffin-embedded, trypsin-digested thyroid tissue in 73% of samples. Antibody to thyroid microsomal antigen was detectable by ELISA in 29% of serums. Indirect immunofluorescence showed cytoplasmic fluorescence of thyroid follicular cells in several serums, however, this could not be confirmed as specific for microsomal antigen by absorption trials. Hemagglutination tests using commercially available tanned red cells coated with human antigens and indirect immunofluorescence assays on formalin-fixed tissue without trypsin digestion, on Bouin's fixed tissue, or on cryostat, methanol-fixed sections, were insensitive. Cryostat sections without methanol fixation were unsuitable due to tissue fragility. No method was recommended for routine diagnostic use. The ELISA test, because of its convenience, may be useful as a screening aid or adjunct to the diagnosis of thyroid disease.


The recombination protein RAD52 cooperates with the excision repair protein OGG1 for the repair of oxidative lesions in mammalian cells.
Oxidized bases are common types of DNA modifications. Their accumulation in the genome is linked to aging and degenerative diseases. These modifications are commonly repaired by the base excision repair (BER) pathway. Oxoguanine DNA glycosylase (OGG1) initiates BER of oxidized purine bases. A small number of protein interactions have been identified for OGG1, while very few appear to have functional consequences. We report here that OGG1 interacts with the recombination protein RAD52 in vitro and in vivo. This interaction has reciprocal functional consequences as OGG1 inhibits RAD52 catalytic activities and RAD52 stimulates OGG1 incision activity, likely increasing its turnover rate. RAD52 colocalizes with OGG1 after oxidative stress to cultured cells, but not after the direct induction of double-strand breaks by ionizing radiation. Human cells depleted of RAD52 via small interfering RNA knockdown, and mouse cells lacking the protein via gene knockout showed increased sensitivity to oxidative stress. Moreover, cells depleted of RAD52 show higher accumulation of oxidized bases in their genome than cells with normal levels of RAD52. Our results indicate that RAD52 cooperates with OGG1 to repair oxidative DNA damage and enhances the cellular resistance to oxidative stress. Our observations suggest a coordinated action between these proteins that may be relevant when oxidative lesions positioned close to strand breaks impose a hindrance to RAD52 catalytic activities.


Cytokine treatment of central nervous system infection: efficacy of interleukin-12 alone and synergy with conventional antifungal therapy in experimental cryptococcosis.
Cell-mediated immune responses appear to be critical in the outcome of cryptococcosis. Interleukin-12 (IL-12) was studied for its potential use as a therapeutic agent because of its stimulation of natural killer cells and gamma interferon production by stimulated T cells and natural killer cells. Gamma interferon-activated macrophages are important in host resistance against cryptococcosis. In two separate studies, male BALB/c mice were infected intravenously with Cryptococcus neoformans. In the first study, mice received either no treatment, 5.0 mg of fluconazole alone per kg of body weight per day (by gavage twice daily), or IL-12 subcutaneously at 0.01, 0.1, or 1.0 microgram/day once daily (low-dose study) alone or in combination with 5.0 mg of fluconazole per kg/day. In a second study (high dose), the dosages of IL-12 used were 1.0, 2.5, or 5.0 micrograms/day. Therapy was given for 10 consecutive days, and the number of CFU of C. neoformans remaining in various organs was quantitated 1 or 2 days after administration of the last dose. In the low-dose study, IL-12 at 0.1 or 1.0 microgram reduced the level of brain infection by approximately 10-fold (P < 0.05) and IL-12 at 1.0 or 0.1 microgram/day enhanced the efficacy of fluconazole. In liver, both the efficacy of IL-12 alone (0.01 or 0.1 microgram; P < 0.05) and enhancement of the efficacy of fluconazole (P < 0.05) were seen. No efficacy of IL-12 was seen in spleens or lungs, although spleen weights increased fourfold in mice given 1.0 microgram of IL-12 per day. In the high-dose study, all IL-12 doses alone again reduced the levels of brain infection (5- to 8-fold; P < 0.05) when the two were given in combination. No overt toxicities were observed at any dose, and overall, 1.0 microgram of IL-12 per day was found to be the optimal dosage for reducing infection in the brain. To our knowledge, this is the first demonstration of the efficacy of cytokine therapy in systemic and particularly brain infections with C. neoformans. The stimulation of cell-mediated immunity represents a new approach to therapy and can enhance suboptimal antimicrobial chemotherapy. IL-12 should be considered for further study and for clinical trials. These studies suggest that other opportunistic central nervous system pathogens should also be investigated.


The morphology of human neuroblastoma cell grafts in the kainic acid-lesioned basal ganglia of the rat.
Cells from a human neuroblastoma cell line (SH-SY5Y) have been used to examine their potential suitability as donor cells for neural transplantation. Grafts of SH-SY5Y cells were placed in the basal ganglia of the rat brain 7 days after kainic acid lesions of the striatum. The animals were killed 4 or 8 weeks following grafting, and light and electron microscopic studies showed that the graft formed a well-vascularized compact mass of cells in the host brain. At both time points grafted cells showed evidence of cellular differentiation with process formation, especially at the graft-host interface where there was intermingling of graft and host neuronal process. Electron microscopic studies showed that graft cell processes containing irregularly-shaped, clear vesicles or membrane-bound dense core vesicles, established regions of specialized contact with other graft cells and formed close associations with host neuronal processes. There was little difference between the grafts of different ages, except that in the older grafts there were early signs of neurodegeneration. Since the SH-SY5Y cells used in these grafts express the enzyme tyrosine hydroxylase and synthesize dopamine in vitro, these cells were used in the hope that they may potentially be useful for repairing lesions in the dopamine pathway, such as that seen in Parkinson's disease. Our behavioural studies show that grafting SH-SY5Y cells into the striatum of rats with 6-hydroxydopamine lesions of the median forebrain bundle result in a reduction of amphetamine-induced rotation. However, this was unlikely to be due to dopamine release since there was no tyrosine hydroxylase immunoreactivity seen in the region of the grafts. Thus grafted human neuroblastoma cells survive, establish specialized morphological associations with graft and host processes and improve behavioural deficits resulting from 6-hydroxydopamine lesions. We suggest that grafted differentiated human neuroblastoma cells can interact with cells in the host brain with beneficial effects, and that in the medium-term, neuroblastoma grafts will make useful models for examining graft-host interactions. However, the presence of early degenerative changes in the older grafts suggests that neuroblastoma cells may not be suitable for long-term neural transplantation therapy for neurodegenerative diseases.


Estrogen signaling increases nuclear receptor subfamily 4 group A member 1 expression and energy production in skeletal muscle cells.
Estrogen deficiency has been known to associate with musculoskeletal diseases in women, based on the clinical observations of frequent susceptibility to osteoporosis and sarcopenia among postmenopausal women. In skeletal muscles, estrogen has been assumed to play physiological roles in maintaining muscle mass and strength, although its precise molecular mechanism remains to be elucidated. We have previously shown that estrogen regulates energy metabolism through the downregulation of mitochondrial uncoupling protein 3 (UCP3) in skeletal muscles, which may contribute to the prolonged exercise endurance in female mice. In the present study, we investigated the effects of estrogen on the expression levels of all members of the nuclear receptor superfamily. Microarray analysis showed that the mRNA level of nuclear receptor subfamily 4 group A member 1 (Nr4a1) was upregulated by the transduction of a recombinant adenovirus expressing constitutively active estrogen receptor α (caERα) in differentiated myoblastic C2C12 cells. Thus we assumed that NR4A1 may be an estrogen-inducible gene in myoblastic cells. We also demonstrated that caERα increases the cellular ATP content along with an increase in mitochondrial DNA content in differentiated myoblastic C2C12 cells. In contrast, the knockdown of Nr4a1 using siRNA exhibited reduced ATP generation as well as a decrease in mitochondrial DNA content. Overall, the present study indicates a crosstalk between estrogen signaling and NR4A1 in skeletal muscle cells. We consider that estrogen-dependent NR4A1 upregulation could increase efficient ATP generation in skeletal muscle cells partly through enhancing mitochondrial functions.


Water-soluble nanodiamond.
Reduction of the graphenic edges of annealed nanodiamond by sodium in liquid ammonia leads to a nanodiamond salt that reacts with either alkyl or aryl halides by electron transfer to yield radical anions that dissociate spontaneously into free radicals and halide. The free radicals were observed to add readily to the aromatic rings of the annealed nanodiamond. Nanodiamonds functionalized by phenyl radicals were sulfonated in oleum, and the resulting sulfonic acid was converted to the sodium salt by treatment with sodium hydroxide. The solubility of the salt in water was determined to be 248 mg/L. Nanodiamond functionalized by carboxylic acid groups could be prepared by reacting 5-bromovaleric acid with the annealed nanodiamond salt. The solubility of the sodium carboxylate in water was found to be 160 mg/L.


Leader emotion regulation, leader-member exchange (LMX), and followers' task performance.
Drawing on Social Exchange theory, we investigated the direct link between leaders' emotion regulation strategies (i.e., surface acting and deep acting) and follower task performance. In addition, we investigated the indirect link between leaders' emotion regulation strategies and follower task performance via leader-member exchange (LMX). Using survey data (N = 301) from the banking industry, we found that leader surface acting only has an indirect negative relationship with follower task performance via LMX, while leader deep acting has both a direct and an indirect positive relationship with follower task performance. The result showed that leader emotion regulation strategies perform a key role in enhancing/damaging LMX and that leaders need to be vigilant regarding their own emotional behaviors. That is, they can develop positive relationships with their followers by employing deep acting but that surface acting damages their relationship with followers. Implications of this study, limitations, and future research are discussed.


Spatial and temporal patterns of intraspecific morphological variation in Dactylogyrus simplexus from fathead minnows in Nebraska.
Dactylogyrus simplexus Monaco and Mizelle, 1955, occurs on the gills of fathead minnows (Pimephales promelas). Previous research on parasites of fathead minnows from 3 converging Nebraska streams, Elk Creek, Oak Creek, and West Oak Creek, shows that fish in each stream constitute distinct populations. To determine whether their parasites had diverged structurally in response to such isolation, or in response to seasonal change, we searched for patterns of intraspecific morphometric variation among D. simplexus. Over 3 collection dates in fall 2007, spring 2008, and fall 2009, 203 D. simplexus were collected from Elk and West Oak Creeks. We ran 1-way ANOVA to compare differences in 15 distinct point-to-point measurements of sclerotized parts across sites and collection dates. Significant differences were found in some D. simplexus measurements between Elk and West Oak Creeks for all 3 collection dates, but the characteristics that differed and the trend of variation between the creeks were not consistent over time. Dactylogyrus simplexus from both Elk and West Oak Creeks showed consistent patterns of variation over time for 5 measurements, including hamulus gap width, bar length, marginal hook length, sickle length, and sickle width. In conclusion, D. simplexus demonstrate consistent patterns of seasonal variation, but not spatial.


A novel telencephalon-opto-hypothalamic morphogenetic domain coexpressing Foxg1 and Otp produces most of the glutamatergic neurons of the medial extended amygdala.
Deficits in social cognition and behavior are a hallmark of many psychiatric disorders. The medial extended amygdala, including the medial amygdala and the medial bed nucleus of the stria terminalis, is a key component of functional networks involved in sociality. However, this nuclear complex is highly heterogeneous and contains numerous GABAergic and glutamatergic neuron subpopulations. Deciphering the connections of different neurons is essential in order to understand how this structure regulates different aspects of sociality, and it is necessary to evaluate their differential implication in distinct mental disorders. Developmental studies in different vertebrates are offering new venues to understand neuronal diversity of the medial extended amygdala and are helping to establish a relation between the embryonic origin and molecular signature of distinct neurons with the functional subcircuits in which they are engaged. These studies have provided many details on the distinct GABAergic neurons of the medial extended amygdala, but information on the glutamatergic neurons is still scarce. Using an Otp-eGFP transgenic mouse and multiple fluorescent labeling, we show that most glutamatergic neurons of the medial extended amygdala originate in a distinct telencephalon-opto-hypothalamic embryonic domain (TOH), located at the transition between telencephalon and hypothalamus, which produces Otp-lineage neurons expressing the telencephalic marker Foxg1 but not Nkx2.1 during development. These glutamatergic cells include a subpopulation of projection neurons of the medial amygdala, which activation has been previously shown to promote autistic-like behavior. Our data open new venues for studying the implication of this neuron subtype in neurodevelopmental disorders producing social deficits.


Prevalence of Synchronous Oligopolyposis in Incident Colorectal Cancer: A Population-Based Study.
Colorectal cancer (CRC) is a leading causes of cancer death among men and women. The purpose of this study was to determine the prevalence of oligopolyposis (≥20 synchronous colorectal adenomas) and its associated clinicopathological characteristics in Hispanics with incident CRC. Pathology reports from individuals diagnosed with CRC (2007 to 2011) were obtained from the PR Central Cancer Registry. Colorectal polyp burden was calculated using pathology reports and the data was normalized to colon segment size. Comparisons of demographic and clinicopathological characteristics by synchronous oligopolyposis status (<20 vs. <= *20) were performed using the chi-square or Fisher's exact test. Multivariate logistic regression models were fitted to estimate the adjusted prevalence odds ratios (aPOR), with 95% confidence intervals (CI). All analyses were performed using Stata (v.12.0). Analyses of 1,573 colectomy specimens was performed. Oligopolyposis was observed in 9.47% (149 of 1,573) of the subjects with incident CRC. Increasing age (aPOR50-64 = 1.72, 95% CI: 0.59-5.02; aPOR65-74 = 1.83, 95% CI: 0.64-5.27; aPOR≥75 = 2.67, 95% CI: 0.93-7.64) and proximal CRC tumor location (POR = 2.91, 95% CI:1.98-4.30) were significantly associated with having oligopolyposis at CRC diagnosis. However, subjects diagnosed with CRC at a regional stage (aPORRegional = 0.50, 95% CI: 0.32-0.79) or distant stage (aPORDistant = 0.45, 95% CI: 0.29-0.69) were less likely to have synchronous oligopolyposis (p<0.05). Our findings suggest that genetic syndromes associated with colorectal polyposis may be implicated in a higher than expected number of CRC cases. Individuals with CRC and synchronous oligopolyposis should receive genetic counseling.


Attenuated effect of oxygen on photopigment synthesis in Rhodospirillum centenum.
Rhodospirillum centenum resembles typical nonsulfur photosynthetic bacteria in a number of respects, including its ability to grow either anaerobically as a phototroph or aerobically as a heterotroph. We demonstrate, however, that R. centenum is unusual in its ability to synthesize a functional photosynthetic apparatus regardless of the presence of molecular oxygen. Aerobically expressed photopigments were shown to be functionally active, as demonstrated by the ability of heterotrophically grown cells to grow photosynthetically, without a lag, when suddenly placed under anaerobic conditions. An R. centenum mutant that has acquired the ability to repress synthesis of photopigments in the presence of oxygen was also characterized. Both the wild type and the oxygen-repressed mutant of R. centenum were found to exhibit high light intensity repression of photopigment biosynthesis. The latter result suggests that R. centenum contains separate regulatory circuits for controlling synthesis of its photochemical apparatus by light intensity and oxygen.


Human fibroblast strains showing increased sensitivity or resistance to ethidium bromide.
The sensitivity of a number of human fibroblast cell strains towards the DNA intercalating and mutagenic agent ethidium bromide has been examined. Among the cell strains investigated, 3 were of fetal origin, 6 from clinically normal adult persons, 2 from Lesch-Nyhan individuals and 1 each from persons with 3 genetic disorders, xeroderma pigmentosum, Fanconi anemia and Bloom syndrome, which are known to predispose to cancer. Results of our studies show that cells derived from 2 otherwise normal individuals exhibits a marked sensitivity towards ethidium bromide as compared to the rest of the group. At the same time all 3 cell strains of fetal origin were found to be highly resistant to killing by this agent. These results are discussed in relation to the toxic/mutagenic effects of ethidium bromide.