Raman Optical Activity of 1T-TaS2.
Measurements of optical activity can be readily performed in transparent matter by means of a rotation of transmitted light polarization. In the case of opaque bulk materials, such measurements cannot be performed, making it difficult to assess possible chiral properties. In this work, we present full angular polarization dependencies of the Raman modes of bulk 1T-TaS2, which has recently been suggested to have chiral properties after pulsed laser excitation. We found that a mechanical rotation of the sample does not alter polarization-resolved Raman spectra, which can only be explained by introducing an antisymmetric Raman tensor, frequently used to describe Raman optical activity (ROA). Raman spectra obtained under circularly polarized excitation demonstrate that 1T-TaS2 indeed shows ROA, providing strong evidence that 1T-TaS2 is chiral under the used conditions of laser excitation. Our results suggest that ROA may be used as a universal tool to study chiral properties of quantum materials.


Annotation of plasmid genes.
Good annotation of plasmid genomes is essential to maximise the value of the rapidly increasing volume of plasmid sequences. This short review highlights some of the current issues and suggests some ways forward. Where a well-studied related plasmid system exists we recommend that new annotation adheres to the convention already established for that system, so long as it is based on sound principles and solid experimental evidence, even if some of the new genes are more similar to homologues in different systems. Where a well-established model does not exist we provide generic gene names that reflect likely biochemical activity rather than overall purpose particularly, for example, where genes clearly belong to a type IV secretion system but it is not known whether they function in conjugative transfer or virulence. We also recommend that annotators use a whole system naming approach to avoid ending up with an illogical mixture of names from other systems based on the highest scoring match from a BLAST search. In addition, where function has not been experimentally established we recommend using just the locus tag, rather than a function-related gene name, while recording possible functions as notes rather than in a provisional name.


[The significance of detection of nitrites in oral fluid of healthy people.]
The nitric oxide is a signal molecule in human organism characterized by a wide spectrum of biological effects. The exogenous nitric oxide is formed from food nitrates received with such green leafy vegetables as spinach, parsley, sorrel and also beet, cucumbers and tomatoes. The bacteria in oral cavity metabolize received with food nitrates up to nitrites. The nitrites as some intermediate metabolites of nitric oxide sufficiently exact reflect concentration of nitric oxide. The purpose of study is to examine analytical dependence and efficiency of express-device for detecting nitrites in saliva. The article presents the results of confirmation of testsystem for half-quantitative detection of content of nitrites in saliva. The device represents a hollow tube with a sensorial element within functioning by the principle of "dry chemistry". The concentration of nitrites in oral cavity was measured in 100 healthy people of both genders aged from 16 to 45 years. In case of consuming vegetables every day or 3-5 times a week higher levels of nitrite-anions (14,9-15,7 mg/l) are registered than in case of consuming vegetables and juices 1-2 times a week and rarely (9,9 mg/l). The concentrations of nitrites in saliva both in cases of regular training and low-activity life-style are within the limits of standards (11,9-14,9 mg/l). The average level of nitrites in saliva of participants of experiment with normal pressure made up to 16.5 mg/l that is significantly higher than in individuals from groups with increased and decreased arterial pressure (10,2 and 10,4 mg/l correspondingly).


4-[18F]fluoro-L-m-tyrosine: an L-3,4-dihydroxyphenylalanine analog for probing presynaptic dopaminergic function with positron emission tomography.
4-[18F]Fluoro-L-m-tyrosine (FMT), a biochemical probe of striatal dopaminergic function, has been synthesized as an L-3,4-dihydroxyphenylalanine analog for positron emission tomography. Biochemical characterization of this compound in the rat 30 min after intrajugular administration indicated that in the brain, selective decarboxylation occurred in the striatum, with the formation of 4-fluoro-3-hydroxyphenylethylamine and its metabolites. Positron emission tomography analysis of brain tissue in monkeys (Macaca nemestrina) after intravenous injection of FMT revealed a true time-dependent, specific accumulation of radioactivity in striatum, with a striatum/cerebellum (nonspecific) ratio of 4 at 180 min. Peripheral metabolism accounted for less than 40% of the total radioactivity in arterial blood samples after 120 min. The amino acid remained as the major component throughout the period of investigation (n = 3; 5 min, 95%; 10 min, 85%; 30 min, 67%; 60 min, 62%; 120 min, 60%), with a plasma clearance t 1/2 of 112 min. 3-O-Methylated metabolites were not observed. The substrate specificity of FMT, coupled with its limited in vivo peripheral metabolism, makes it a useful, new biochemical probe for in vivo, noninvasive evaluation of central dopaminergic mechanisms.


Curve Progression in Adolescent Idiopathic Scoliosis Does Not Match Skeletal Growth.
Determining the peak growth velocity of a patient with adolescent idiopathic scoliosis (AIS) is important for timely treatment to prevent curve progression. It is important to be able to predict when the curve-progression risk is greatest to maximize the benefits of any intervention for AIS. The distal radius and ulna (DRU) classification has been shown to accurately predict skeletal growth. However, its utility in predicting curve progression and the rate of progression in AIS is unknown. (1) What is the relationship between radius and ulna grades to growth rate (body height and arm span) and curve progression rate? (2) When does peak curve progression occur in relation to peak growth rate as measured by months and by DRU grades? (3) How many months and how many DRU grades elapse between peak curve progression and plateau? This was a retrospective analysis of a longitudinally maintained dataset of growth and Cobb angle data of patients with AIS who presented with Risser Stages 0 to 3 and were followed to maturity at Risser Stage 5 at a single institute with territory-wide school screening service. From June 2014 to March 2016, a total of 513 patients with AIS fulfilled study inclusion criteria. Of these, 195 were treated with bracing at the initial presentation and were excluded. A total of 318 patients with AIS (74% girls) with a mean age of 12 ± 1.5 years were studied. For analysis, only data from initial presentation to commencement of intervention were recorded. Data for patients during the period of bracing or after surgery were not used for analysis to eliminate potential interventional confounders. Of these 318 patients, 192 were observed, 119 were braced, and seven underwent surgery. Therefore 192 patients (60.4%) who were observed were followed up until skeletal maturity at Risser Stage 5; no patients were lost to followup. The mean curve magnitude at baseline was 21.6 ± 4.8. Mean followup before commencing intervention or skeletal maturity was 4.3 ± 2.3 years. Standing body height, arm span, curve magnitude, Risser stage, and DRU classification were studied. A subgroup analysis of 83 patients inclusive of acceleration, peak, and deceleration progression phases for growth and curve progression was studied to determine any time lag between growth and curve progression. Results were described in mean ± SD. There was positive correlation between growth rate and curve progression rate for body height (r = 0.26; p < 0.001) and arm span (r = 0.26; p < 0.001). Peak growth for body height occurred at radius grade (R) 6 (0.56 ± 0.29 cm/month) and ulna grade (U) 4 (0.65 ± 0.31 cm/month); peak change in arm span occurred at R5 (0.67 ± 0.33 cm/month) and U3 (0.67 ± 0.22 cm/month); and peak curve progression matched with R7 (0.80 ± 0.89 cm/month) and U5 (0.84 ± 0.78 cm/month). Subgroup analysis confirmed that peak curve progression lagged behind peak growth rate by approximately 7 months or one DRU grade. The mean time elapsed between the peak curve progression rate and the plateau phase at R9 U7 was approximately 16 months, corresponding to two DRU grades. By using a standard skeletal maturity parameter in the DRU classification, this study showed that the maximal curve progression occurs after the peak growth spurt, suggesting that the curve should be monitored closely even after peak growth. In addition, the period of potential curve continuing progression extends nearly 1.5 years beyond the peak growth phase until skeletal maturity. Future studies may evaluate whether by observing the trend of growth and curve progression rates, we can improve the outcomes of interventions like bracing for AIS. Level II, prognostic study.


Differentiation of mononuclear blood cells into macrophages, fibroblasts and endothelial cells in thrombus organization.
The organization of thrombi and emboli may be performed exclusively by mononuclear blood cells which represent precursors of various mesenchymal cell types. Between the 10th and 20th day after the onset of blood clotting, mononuclear cells within the fibrinous matrix differentiate into (1) macrophages responsible for hematoclasia and hematophagocytosis, (2) endothelial cells lining autolytic slits in the fibrinous matrix and forming new capillaries, and (3) fibroblasts and even smooth muscle cells building up a young mesenchymal connective tissue.


[The application of genotyping in the complicated ABO blood group type].
To investigate the application of ABO blood group genotyping in complicated ABO blood group type. Ten specimens of complicated ABO blood group were genotyped by sequence specific primer PCR (PCR -SSP), and confirmed by DNA sequencing and alignment. Six hundred and ten blood samples typed by ABO immunoassay were as control of genotyping. Ten cases of complicated blood type were identified by high resolution PCR- SSP as rare ABO blood groups: cis-AB01 (3 cases), B(A)04 (2 cases), cisAB02, B(A)02, Bel03, Bw12 and Ael05, confirmed by DNA sequencing. Genotyping and serotype detected 610 cases ABO blood group were coincident, and the frequency of A, B, AB and O were as 28.69%, 27.54%, 8.2% and 35.57% respectively. According to the genotypes, the highest frequency subgroup was O1 (32.87%), the lowest was A2 (0.66%). PCR -SSP could type the ABO blood group accurately, but also the sub-group of blood type. However, special designed high resolution PCR -SSP or DNA sequencing is needed to identify the complicated blood groups.


Residual tobacco smoke pollution in used cars for sale: air, dust, and surfaces.
Regular tobacco use in the enclosed environment of a car raises concerns about longer-term contamination of a car's microenvironment with residual secondhand smoke pollutants. This study (a) developed and compared methods to measure residual contamination of cars with secondhand smoke, (b) examined whether cars of smokers and nonsmokers were contaminated by secondhand smoke, and (c) how smoking behavior and restrictions affected contamination levels. Surface wipe, dust, and air samples were collected in used cars sold by nonsmokers (n = 20) and smokers (n = 87) and analyzed for nicotine. Sellers were interviewed about smoking behavior and restrictions, and car interiors were inspected for signs of tobacco use. Cars of smokers who smoked in their vehicles showed significantly elevated levels of nicotine (p < .001) in dust, on surfaces, and in the air compared with nonsmoker cars with smoking ban. When smokers imposed car smoking bans, air nicotine levels were significantly lower (p < .01), but dust and surface contamination levels remained at similar levels. Smoking more cigarettes in the car and overall higher smoking rate of the seller were significantly associated with higher secondhand smoke contamination of the car (p < .001). Use of a cutpoint for nicotine levels from surface wipe samples correctly identified 82% of smoker cars without smoking bans, 75% of smoker cars with bans, and 100% of nonsmoker cars. Surface nicotine levels provide a relatively inexpensive and accurate method to identify cars and other indoor environments contaminated with residual secondhand smoke. Disclosure requirements and smoke-free certifications could help protect nonsmoking buyers of used cars.


Intra- and interspecific embryo transfer.
The procedures that are collectively referred to as embryo transfer (ET) have many uses. They were first used as research tools to study fetal-maternal physiology. Since the first successful mammalian embryo transfer in 1890, ET has been utilized for enhancement of genetic selection; diagnosis and treatment of infertility; control of infectious disease transmission; screening for genetic defects; propagation of rare and endangered species; and the study of developmental biology. Most of the embryo transfers have been intraspecific. A listing of the species includes rabbit, rat, sheep, mouse, goat, cattle, pig, hamster, ferret, mink, horse, baboon, cat, dog, water buffalo. In two species, rhesus monkey and humans, the successful embryo transfers have been limited to within-animal, homologous replacement of the embryos. There have been a few successful interspecific embryo transfers. The most common were between Bos taurus and B. indicus cattle. Other interspecific transfers involved Bos gaurus and B. taurus, cattle; Ovis musimon and O. aries, sheep; Equus asinus and E. caballus, horses. There are several examples of intergeneric embryo transfers in which embryos implanted but did not develop to term: sheep and goat, mouse and rat. The factors that determine the degree of compatibility between embryos and uteri of various species and genera are not clearly understood. The ability to hybridize successfully is probably a dependable indication of compatibility for embryo transfer. The limits of tolerance for differences between the donor and recipient in such factors as placental structure and gestation length have not been defined, but the recently developed technique of inner cell mass transfer will be very useful in such studies.


Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport.
Methotrexate (MTX) has been used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of inflammatory diseases as well as malignancies. Especially at high MTX dosages, severe adverse effects with this combination may occur, usually resulting from an impaired renal elimination. It has been shown that the mechanism of this interaction cannot be fully attributed to inhibition of basolateral MTX uptake in renal proximal tubules. Here, we studied the effect of various NSAIDs on MTX transport in membrane vesicles isolated from cells overexpressing the proximal tubular apical efflux transporters human multidrug resistance protein (MRP) 2/ABCC2 and MRP4/ABCC4. MTX was transported by MRP2 and MRP4 with Km values of 480 +/- 90 and 220 +/- 70 microM, respectively. The inhibitory potency of the NSAIDs was generally higher against MRP4- than MRP2-mediated MTX transport, with therapeutically relevant IC50 values, ranging from approximately 2 microM to 1.8 mM. Salicylate, piroxicam, ibuprofen, naproxen, sulindac, tolmetin, and etodolac inhibited MRP2- and MRP4-mediated MTX transport according to a one-site competition model. In some cases, more complex interaction patterns were observed. Inhibition of MRP4 by diclofenac and MRP2 by indomethacin and ketoprofen followed a two-site competition model. Phenylbutazone stimulated MRP2 and celecoxib MRP4 transport at low concentrations and inhibited both transporters at high concentration. Our data suggest that the inhibition by NSAIDs of renal MTX efflux via MRP2 and MRP4 is a potential new site and mechanism contributing to the overall interaction between these drugs.


What is the next structure? Guessing enhances L2 syntactic learning in a syntactic priming task.
Previous psycholinguistic research has shown that Second Language (L2) speakers could learn from engaging in prediction. Few works have directly examined the relationship between prediction and L2 syntactic learning. Further, relatively limited attention has been paid to the effects of two linguistic factors in this area: structure type and L2 proficiency. Using a mixed experimental design, 147 L2 Arabic speakers with varying L2 proficiency levels completed two syntactic priming experiments, each targeting a different structure: (a) the dative and (b) Temporal Phrases (TP). The experimental conditions required participants to predict what the upcoming sentence's structure would be. The experimental conditions differed in the degree of engagement in prediction error. Results suggested that Arabic L2 speakers at different proficiency levels showed enhanced priming and short-term learning for two syntactic structures (PO, fronted TP) when (a) instructed to guess only (constrained condition) as well as when (b) instructed to guess and compute the prediction error (unconstrained condition), relative to the controls. These results imply a guessing benefit for priming and short-term learning. Participants also experienced different priming effects by structure type, but there was no significant effect for proficiency. The theoretical and practical implications of these findings are discussed.


Strategic offloading of delayed intentions into the external environment.
In everyday life, we often use external artefacts such as diaries to help us remember intended behaviours. In addition, we commonly manipulate our environment, for example by placing reminders in noticeable places. Yet strategic offloading of intentions to the external environment is not typically permitted in laboratory tasks examining memory for delayed intentions. What factors influence our use of such strategies, and what behavioural consequences do they have? This article describes four online experiments (N = 1196) examining a novel web-based task in which participants hold intentions for brief periods, with the option to strategically externalize these intentions by creating a reminder. This task significantly predicted participants' fulfilment of a naturalistic intention embedded within their everyday activities up to one week later (with greater predictive ability than more traditional prospective memory tasks, albeit with weak effect size). Setting external reminders improved performance, and it was more prevalent in older adults. Furthermore, participants set reminders adaptively, based on (a) memory load, and (b) the likelihood of distraction. These results suggest the importance of metacognitive processes in triggering intention offloading, which can increase the probability that intentions are eventually fulfilled.


Genetic variation in PTPN22 corresponds to altered function of T and B lymphocytes.
A variant of the PTPN22 gene, 1858C/T, is associated with an increased risk for the development of a wide array of autoimmune disorders. It is known that the protein tyrosine phosphatase Lyp encoded by this gene has an inhibitory effect on the proximal TCR signaling pathways. However, the consequences of carrying this variant and the mechanism by which it contributes to the development of autoimmunity are poorly understood. In this study, we demonstrate that homozygosity for this variant results in a profound deficit in T cell responsiveness to Ag stimulation. Heterozygosity for the variant allele is associated with reduced responsiveness of CD4+ memory T cells, characterized by diminished calcium mobilization, expression of CD25, and IL-10 production upon TCR stimulation. Additionally, the presence of the variant allele is associated with an increase in circulating memory T cells. We further demonstrate that these effects are not limited to the T cell compartment. Individuals with the variant allele have fewer memory B cells and these cells display a reduced response to stimulation via the BCR indicative of a B cell intrinsic defect. By identifying an immunologic phenotype in healthy subjects which correlates with the PTPN22 1858C/T genotype, we can now explore specific hypotheses regarding pathogenesis of diseases associated with the PTPN22 1858T variant.


Generation of high-order harmonics and attosecond pulses in the water window via nonlinear propagation of a few-cycle laser pulse.
We theoretically and computationally study the generation of high-order harmonics in the water window from a semi-infinite gas cell where a few-cycle, carrier-envelope-phase-controlled 1.7-µm driving laser pulse undergoes nonlinear propagation via optical Kerr effect (self-focusing) and plasma defocusing. Our calculation shows that high harmonic signals are enhanced for extended propagation distances and furthermore, isolated attosecond pulses in the water window can be generated from the semi-infinite gas cell. This enhancement is attributed mainly to better phase matching for extended propagation distances achieved via nonlinear propagation and resulting intensity stabilization.


Physiological and anatomical differentiation of two sympatric weed populations.
In the vineyards of Rhineland-Palatinate (Germany), two different types of Shepherd's Purse (Capsella bursa-pastoris) coexist: (1) the common type called 'wild type', and (2) the decandric type called Capsella apetala or 'Spe' with four stamens in place of the four petals. In this study, we compare the anatomical and physiological characters of rosette leaves of the respective types. Progeny of individual plants was cultivated in growth chambers under low- and high-light conditions. Under low-light conditions, the stomata densities of the adaxial and abaxial epidermis did not differ between the two types. When grown under high-light conditions, wild type and Spe, both exhibited increased stomata densities compared to low-light conditions, but Spe to a lesser extent than the wild type. The maximal photosynthetic capacity of Spe was lower in both, low-light and high-light conditions compared to wild-type plants. Under all CO2 concentrations, Spe seemed to be less productive. The less effective CO2 assimilation of the Spe mutant C. apetala was accompanied by later flowering. This fact prolonged the vegetative phase of Spe by about two weeks and was sufficient for the maintenance of both populations stably over years.


Curiosity evolves as information unfolds.
When people feel curious, they often seek information to resolve their curiosity. Reaching resolution, however, does not always occur in a single step but instead may follow the accumulation of information over time. Here, we investigated changes in curiosity over a dynamic information-gathering process and how these changes related to affective and cognitive states as well as behavior. Human participants performed an Evolving Line Drawing Task, during which they reported guesses about the drawings' identities and made choices about whether to keep watching. In Study 1, the timing of choices was predetermined and externally imposed, while in Study 2, participants had agency in the timing of guesses and choices. Using this dynamic paradigm, we found that even within a single information-gathering episode, curiosity evolved in concert with other emotional states and with confidence. In both studies, we showed that the relationship between curiosity and confidence depended on stimulus entropy (unique guesses across participants) and on guess accuracy. We demonstrated that curiosity is multifaceted and can be experienced as either positive or negative depending on the state of information gathering. Critically, even when given the choice to alleviate uncertainty immediately (i.e., view a spoiler), higher curiosity promoted continuing to engage in the information-gathering process. Collectively, we show that curiosity changes over information accumulation to drive engagement with external stimuli, rather than to shortcut the path to resolution, highlighting the value inherent in the process of discovery.


Respiratory depressant effects of GABA alpha- and beta-receptor agonists in the cat.
The aim of this study was to evaluate the cardiorespiratory effects of intravenously administered gamma-aminobutyric acid (GABA) alpha-(4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol, THIP) and beta-(baclofen) receptor agonists and to locate the site of action of these drugs in the brain. THIP and baclofen were administered to alpha-chloralose-anesthetized cats while minute ventilation (VE), arterial blood pressure (AP), and heart rate were monitored. THIP, in doses of 0.5 to 2 mg/kg decreased VE, tidal volume (VT), and AP. No changes in respiratory rate (f) or inspiratory (TI) or expiratory (TE) duration were observed. Baclofen, in doses of 0.5 to 4 mg/kg, decreased VE, f, and AP. VT and TI increased and an "apneustic" breathing pattern was seen. THIP (9.5 micrograms), applied bilaterally to the glycine-sensitive area of the ventral medulla, reproduced the effects seen with intravenous administration. Application of 10 micrograms of bicuculline bilaterally to this area reversed the effects of intravenous THIP but not those of baclofen. Baclofen (5.6-56 micrograms), administered by the intracisternal route, produced the same respiratory effects seen with intravenous administration. We conclude that activation of GABA alpha- and beta-receptors produces cardiorespiratory depression. However, this is accomplished by different mechanisms and by actions exerted at different central nervous system sites.


Androstene-3,5-dienes as ER-beta selective SERMs.
A series of androstene-3,5-diene derivatives were prepared. Despite lacking the C-3 hydroxyl previously believed necessary for ER activity, some of the analogs retained surprising affinity for ER-beta. For example, diene 4 retained excellent selectivity and potency as an ER-beta agonist and was more selective for ER-beta over the androgen receptor (AR).


The History of Sleep Surgery.
Snoring and the subsequent diagnosis of obstructive sleep apnea (OSA) was a life-threatening medical condition with no available treatment until the late 20th century. An early description of OSA was provided by Charles Dickens in his 1836 novel Pickwick Papers with the description of a "fat boy" who was thought to be lazy and always falling asleep but likely displayed hypersomnolence from OSA. It was not until 1976 that Ikematsu first described uvulopalatopharyngoplasty (UPPP) as an alternative surgical treatment of "snoring," with a reported cure rate of 81%. The only other surgical procedure for OSA was permanent tracheostomy, but patients suffered from social stigma from the visible stoma with skin flaps and complications such as tracheal granulomas and tracheitis. UPPP was introduced in the USA as an alternative to permanent tracheostomy by Fujita in 1981. Since then, multiple surgical approaches and combinations of approaches have surfaced, with variable success rates.


Application of endoscopy to treat mandibular keratocystic odontogenic tumors.
The aim of this study was to evaluate the feasibility of endoscopy to remove keratocystic odontogenic tumors (KCOTs) with virtual 3D mandibular images. Fifteen patients (mean age, 40.27±14.58 years) who underwent endoscopic mandibular KCOT enucleation between May 2009 and October 2009 were included. Virtual 3D mandibular reconstructions derived from computed tomography (CT) imaging were generated for all patients. Recurrence and pathological fracture were evaluated as the primary outcome variables at 1 and 12 months after operation. Secondary infection and inferior alveolar nerve injury were evaluated as the secondary outcome variables at 1 and 6 months after operation. None of the 15 patients exhibited signs of recurrence or pathological fracture after operation. During long-term follow-up, no symptoms of inferior alveolar nerve injury or secondary infection were observed and no signs of recurrence were found in any of the patients. Endoscopy helps surgeons to remove mandibular KCOTs with small incisions. Moreover, endoscopy can provide clear and magnified views and help to avoid damage to the inferior alveolar neurovascular bundle. Therefore, under the support of preoperative virtual 3D mandibular images, the application of endoscopy to remove the tumors should be considered to be a treatment option for KCOTs.


Isolation and partial characterization of insulin of the honeybee (Apis mellifica).
In the honeybee (Apis mellifica), insulin-like material was partially purified with acid ethanol extractions by a classic method for recovering insulin and following gel filtration on a Sephadex G-50 column. The preparations were characterized by their ability to cross-react with porcine insulin antibodies. Insulin-like biological activity was demonstrated using the insulin bioassay. Stimulation of glucose oxidation or lipogenesis was measured by isolated rat adipocytes. Insulin seems to be more widespread in invertebrates than was previously assumed.


Bovine papillomavirus type 1 E6-induced sensitization to apoptosis is distinct from its transforming activity.
The bovine papillomavirus type 1 (BPV-1) E6 oncoprotein induces tumorigenic transformation of murine C127 cells and stimulates transcription when targeted to a promoter. We have previously shown that C127 cells expressing BPV-1 E6 exhibited increased tumor necrosis factor alpha (TNF)-mediated apoptosis. To understand the mechanisms by which BPV-1 E6 sensitizes cells to apoptosis and to investigate the relevance of E6-enhanced apoptosis to its other biological activities, we analyzed a BPV-1 E6 mutant (491, with four amino acids deleted at the C-terminus) for its ability to sensitize C127 cells to apoptosis. The result was then compared with the E6 mutant's ability to transform cells, to activate transcription, and to associate with known cellular binding proteins. Our data indicated that the transcriptional activation function of BPV-1 E6 correlated with sensitization of cells to TNF-mediated apoptosis. Moreover, functions required for BPV-1 E6-mediated sensitization of cells to apoptosis are distinct from those required for transformation. A potential role of paxillin in E6 sensitization of cells to apoptosis is implicated. These results thus indicate that sensitization of cells to TNF-induced apoptosis represents a novel function of BPV-1 E6.


Can a Conversation Between Mesenchymal Stromal Cells and Macrophages Solve the Crisis in the Inflamed Intestine?
Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract characterized by an exacerbated mucosal immune response. Macrophages play pivotal roles in the maintenance of gut homeostasis but they are also implicated in the pathogenesis of IBD. They are highly plastic cells and their activation state depends on the local environment. In the healthy intestine, resident macrophages display an M2 phenotype characterized by inflammatory energy, while inflammatory M1 macrophages dominate in the inflamed intestinal mucosa. In this regard, modifying the balance of macrophage populations into an M2 phenotype has emerged as a new therapeutic approach in IBD. Multipotent mesenchymal stromal cells (MSCs) have been proposed as a promising cell-therapy for the treatment of IBD, considering their immunomodulatory and tissue regenerative potential. Numerous preclinical studies have shown that MSCs can induce immunomodulatory macrophages and have demonstrated that their therapeutic efficacy in experimental colitis is mediated by macrophages with an M2-like phenotype. However, some issues have not been clarified yet, including the importance of MSC homing to the inflamed colon and/or lymphoid organs, their optimal route of administration or whether they are effective as living or dead cells. In contrast, the mechanisms behind the effect of MSCs in human IBD are not known and more data are needed regarding the effect of MSCs on macrophage polarization that would support the observation reported in the experimental models. Nevertheless, MSCs have emerged as a novel method to treat IBD that has already been proven safe and with clinical benefits that could be administered in combination with the currently used pharmacological treatments.


Immunohistochemical identification of caprine arthritis-encephalitis virus in paraffin-embedded specimens from naturally infected goats.
The expression of caprine arthritis-encephalitis virus capsid protein was studied in seropositive naturally infected asymptomatic goals (10< seropositive naturally infected encephalitic kids (12) and goats (4), and noninfected control goats (3). Rabbit antiserum to recombinant viral capsid and matrix proteins were used in a biotin-streptavidin-alkaline phosphatase complex immunohistochemical method on sections of formalin- and ethanol-fixed tissue specimens. Macrophages in inflamed areas of the lung (8/12), in the brain (5/16), and in the spinal cord (4/16) from encephalitic animals harbored viral antigens, as revealed by immunohistochemistry and use of a capsid protein-specific antiserum. Altogether 12/16 encephalitic animals tested positive for viral antigen. Viral antigens were found in 5/10 seropositive asymptomatic goals in macrophages located in the lung (3), the udder (1), and the medulla of lymph nodes (4). None of the control animals tested positive for viral antigen. Ethanol fixation showed highest sensitivity, and the lowest antigen concentration that revealed a positive signal discernible from background was twofold higher in ethanol-fixed specimens than in formalin-fixed specimens. The evaluation was performed on artificial antigen substrates embedded with defined concentrations of recombinant viral capsid protein. Immunohistochemistry is a valuable supplement to the methods presently available for diagnosis in cases suspicious of caprine arthritis-encephalitis.


Cytokeratins and cytokeratin filaments in subpopulations of cultured human and rodent cells of nonepithelial origin: modes and patterns of formation.
Using immunofluorescence microscopy, we observed that in several established cell culture lines derived from different nonepithelial tissues and species, cells spontaneously emerge, usually at low frequencies, which contain cytoplasmic structures decorated by antibodies specific for cytokeratins 8 and 18. This phenomenon was further examined at both the protein (gel electrophoreses of cytoskeletal proteins, followed by immunoblotting) and the RNA (Northern blots, "nuclear run-on" analysis, in situ hybridization) level. Positive cell lines included simian virus (SV40)-transformed human fibroblasts (HF-SV80, WI-38 VA13), human astrocytic glioma cells (U333 CG/343MG), rat (RVF-SMC) and hamster (BHK-21/13) cells derived from vascular smooth muscle and murine sarcoma MS-180 cells. In two cell lines (HF-SV80 and BHK-21/13), the frequency of the cytokeratin-containing cells and of the cytokeratin fibril arrays per cell was drastically increased upon treatment with 5-azacytidine. The structural appearance of the cytokeratins was variable in the different cell lines but could also differ among cells of the same culture: While small granular or comma-shaped structures or bizarrely shaped filament arrays prevailed in WI-38, RVF and normally grown BHK-21 cells, most of the other lines revealed extended normal-looking, fibrillar arrays. In one line (MS-180), the appearance of cytokeratins was associated with a morphological change, as it was only found in a subpopulation of cells that had lost their typical elongated and spindle-shaped phenotype and assumed a rounded ("coccoid") shape. Our results show that the expression of the genes encoding cytokeratins 8 and 18 is not necessarily restricted to programs of epithelial differentiation and that factors stochastically effective appear in cultured cell lines that allow the synthesis of these cytoskeletal components. Mechanisms possibly involved in this spontaneous and selective advent of cytokeratins 8 and 18 and implications for tumor diagnosis are discussed.


Social desirability is associated with some physical activity, psychosocial variables and sedentary behavior but not self-reported physical activity among adolescent males.
This study examined whether controlling for social desirability improved the association between self-reported and objectively measured physical activity among adolescent males and the extent that psychosocial variables predict physical activity after controlling for social desirability. Participants (n=447) were 10- to 14-year old Houston Boy Scouts. Participants completed self-reports of physical activity, sedentary behavior, preferences, self-efficacy and social desirability and wore an MTI accelerometer for 3 days. Correlations were conducted among variables. Regression models were performed to examine the relationships between objectively measured (accelerometer) and self-reported physical activity, objectively measured physical activity and psychosocial variables and self-reports of physical activity and psychosocial variables. All models controlled for social desirability. There were weak associations between self-reported and objectively measured physical activity measures that were slightly improved after controlling for social desirability. Psychosocial variables were strongly associated with self-reports of physical activity, but weakly associated with accelerometer physical activity. Social desirability was positively associated with physical activity preferences (r=0.169) and self-efficacy (r=0.118) and negatively associated (r=-0.158) with self-reported sedentary behavior. Differences in the strength of relationships between self-reported and objectively measured physical activity and psychosocial variables were not a function of social desirability.


Whether verbal and visuospatial working memory play different roles in pupil's mathematical abilities.
Previous research showed a significant association between mathematics and working memory (WM). However, evidence regarding the different effects of verbal and visuospatial WM on mathematical abilities was very limited. The current research aims to explore the relationship between verbal and visuospatial WM with mathematical abilities, and how this relationship is moderated by age and math domains. We also wonder whether the results would change when we use several tests for each component and use a latent variable approach for more reliable measurement. 131 first graders and 144 fifth graders from a primary school in Hangzhou, Zhejiang province, China, participated our research. All participants completed three verbal and three visuospatial WM tasks, mathematics tests, and fluid intelligence test. Hierarchical multiple regression analysis was used to examine the pattern of relations among these constructs. The results of hierarchical multiple regression analysis showed that verbal WM significantly predicted mathematics achievement for fifth graders, while failed for first graders. However, visuospatial WM played a substantive role in both graders' mathematical performance. The different role of the two WM components also depend on various fields of mathematics. Our results indicated the distinct influence of verbal and visuospatial WM on primary school students' mathematical abilities and highlighted the developmental and domain-specific effects of WM on mathematics.


Differences in brain-derived neurotrophic factor between neonates born to mothers with normal and low ferritin.
Maternal iron deficiency in late pregnancy, labor, and the postpartum period has an indirect impact to decrease neurotrophin concentration in the fetal hippocampus, namely brain-derived neurotrophic factor (BDNF). It plays an important role in the development of learning, memory, and behavior. The aim of this study was to determine the differences in BDNF between neonates born to mothers with normal and low ferritin. This was an observational study with a cross-sectional design involving 20 term pregnant women with normal ferritin (>=12 ng/mL) and 20 term pregnant women with low ferritin (<12 ng/mL). Samples were taken from Yarsi hospital, BMC hospital, and Hardi clinic located in Padang, from August 2015 to February 2016. Umbilical cord plasma was examined directly after delivery using an enzymelinked immunosorbent assay (ELISA) employed at the Biomedical Laboratory of Andalas University. Mean differences were statistically assessed by independent samples t-test. Plasma BDNF concentrations in neonates born to mothers with normal and low ferritin were 3.81±1.37 ng/mL and 2.78±1.19 ng/mL, respectively (p=0.015). Plasma BDNF was lower in neonates born to mothers with low serum ferritin.


Cognitive performance in long-term abstinent elderly alcoholics.
To date, there is a wealth of literature describing the deleterious effects of active alcoholism on cognitive function. There is also a growing body of literature on the extent of cognitive recovery that can occur with abstinence. However, there is still a dearth of published findings on cognitive functioning in very long-term abstinence alcoholics, especially in the elderly population. The current study examines 91 elderly abstinent alcoholics (EAA) (49 men and 42 women) with an average age of 67.3 years, abstinent for an average of 14.8 years (range 0.5 to 45 years), and age and gender comparable light/nondrinking controls. The EAA group was divided into 3 subgroups: individuals that attained abstinence before age 50 years, between the ages 50 and 60 years, and after age 60 years. Attention, verbal fluency, abstraction/cognitive flexibility, psychomotor, immediate memory, delayed memory, reaction time, spatial processing, and auditory working memory were assessed. The AMNART and cranium size were used as estimates of brain reserve capacity, and the association of all variables with alcohol use measures was examined. Overall, the EAA groups performed comparably to controls on the assessments of cognitive function. Only the abstinent in group before 50 years of age performed worse than controls, and this was only in the domain of auditory working memory. EAAs had larger craniums than their controls. This effect was strongest for those who drank the longest and had the shortest abstinence. Such individuals also performed better cognitively. Our data showed that elderly alcoholics that drank late into life, but with at least 6 months abstinence can exhibit normal cognitive functioning. Selective survivorship and selection bias probably play a part in these findings. Cognitively healthier alcoholics, with more brain reserve capacity, may be more likely to live into their 60s, 70s, or 80s of age with relatively intact cognition, and to volunteer for studies such as this. Our results do not imply that all elderly alcoholics with long-term abstinence will attain normal cognition.


Alternative treatment of intracranial hypotension presenting as postdural puncture headaches using epidural fibrin glue patches: two case reports.
Intracranial hypotension is a neurologic syndrome characterized by orthostatic headaches and, radiographically, by dural thickening and enhancement as well as subdural collections. Several of etiologies exist, including surgical dural violations, lumbar puncture, or spontaneous cerebrospinal fluid leak. Current management includes conservative management consisting of bed rest, caffeine, and hydration. When conservative management fails, open surgical or percutaneous options are considered. Currently, the gold standard in percutaneous management of intracranial hypotension involves the epidural injection of autologous blood. Recently, some therapies for intracranial hypotension have employed the use of epidural fibrin glue. Two cases of patients with persistent postdural puncture headaches are presented. Epidural fibrin glue injection alleviated the orthostatic headaches of two patients with intracranial hypotension. Although consideration must be afforded for the potential risks of viral transmission and aseptic meningitis, the utilization of epidural fibrin glue injection as an alternative or adjunct to the epidural blood patch in the treatment of intracranial hypotension should be further investigated.


Control of plant virus diseases in cool-season grain legume crops.
Cool-season grain legume crops become infected with a wide range of viruses, many of which cause serious diseases and major yield losses. This review starts by discussing which viruses are important in the principal cool-season grain legume crops in different parts of the world, the losses they cause and their economic impacts in relation to control. It then describes the main types of control measures available: host resistance, phytosanitary measures, cultural measures, chemical control, and biological control. Examples are provided of successful deployment of the different types of measures to control virus epidemics in cool-season grain legume crops. Next it emphasizes the need for integrated approaches to control because single control measures used alone rarely suffice to adequately reduce virus-induced yield losses in these crops. Development of effective integrated disease management (IDM) strategies depends on an interdisciplinary team approach to (i) understand the ecological and climatic factors which lead to damaging virus epidemics and (ii) evaluate the effectiveness of individual control measures. In addition to using virus-resistant cultivars, other IDM components include sowing virus-tested seed stocks, selecting cultivars with low seed transmission rates, using diverse phytosanitary or cultural practices that minimize the virus source or reduce its spread, and using selective pesticides in an environmentally responsible way. The review finishes by briefly discussing the implications of climate change in increasing problems associated with control and the opportunities to control virus diseases more effectively through new technologies.


Learning from the Brain: Bioinspired Nanofluidics.
The human brain completes intelligent behaviors such as the generation, transmission, and storage of neural signals by regulating the ionic conductivity of ion channels in neuron cells, which provides new inspiration for the development of ion-based brain-like intelligence. Against the backdrop of the gradual maturity of neuroscience, computer science, and micronano materials science, bioinspired nanofluidic iontronics, as an emerging interdisciplinary subject that focuses on the regulation of ionic conductivity of nanofluidic systems to realize brain-like functionalities, has attracted the attention of many researchers. This Perspective provides brief background information and the state-of-the-art progress of nanofluidic intelligent systems. Two main categories are included: nanofluidic transistors and nanofluidic memristors. The prospects of nanofluidic iontronics' interdisciplinary progress in future artificial intelligence fields such as neuromorphic computing or brain-computer interfaces are discussed. This Perspective aims to give readers a clear understanding of the concepts and prospects of this emerging interdisciplinary field.


[Assessment of vitamins and minerals intake with supplements during breast-feeding].
Assessment of supplements intake during breast-feeding was aim of the work. Seventy three women were examined in age 19-42 years coming from the Lublin province. The information about applying supplements during breast-feeding was obtained using questionnaire method. Achieved results served for calculations of taking vitamins and minerals coming from supplements. During breast-feeding 48% women accepted supplements. Average intakes of vitamin B2 (113%), B6 (120%), folic acid (144%) and vitamin D (166%) from supplements were above 100% recommended values. The highest average consumption was noted for iron (229% of recommended value), however the lowest on level 10-35% recommendations for vitamin A (33%), calcium (11%), selenium (12%) and magnesium (20%). Nearly 100% of the norm realization was obtained in case of the vitamin C (93%), E (102%), PP (105%), B1 (107%) and zinc (99%).


Large-Scale Multi-Omics Genome-Wide Association Studies (Mo-GWAS): Guidelines for Sample Preparation and Normalization.
Both gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) are widely used metabolomics approaches to detect and quantify hundreds of thousands of metabolite features. However, the application of these techniques to a large number of samples is subject to more complex interactions, particularly for genome-wide association studies (GWAS). This protocol describes an optimized metabolic workflow, which combines an efficient and fast sample preparation with the analysis of a large number of samples for legume crop species. This slightly modified extraction method was initially developed for the analysis of plant and animal tissues and is based on extraction in methyl tert-butyl ether: methanol solvent to allow the capture of polar and lipid metabolites. In addition, we provide a step-by-step guide for reducing analytical variations, which are essential for the high-throughput evaluation of metabolic variance in GWAS.


[Liver injury induced by immune checkpoint inhibitor-therapy : Example of an immune-mediated drug side effect].
Drug-induced liver injury is increasing, especially in elderly patients with polymedication and multimorbidity. Clinicopathologic correlation of immune-mediated liver injury, specifically liver injury following therapy with immune checkpoint inhibitors against PD-1, PDL-1, and CTLA4. Histologic assessment of liver biopsies of nine patients after therapy with immune checkpoint inhibitors and correlation with clinical parameters. In all nine patients, liver injury was apparent after variable administration of immune checkpoint inhibitors. Transaminase levels were increased up to a maximum of 3818 U/l. Liver histology showed liver injury resembling autoimmune hepatitis respective cholangitis. In two patients, veno-occlusive disease was seen. Corticosteroid therapy was initiated in eight patients, subsequently four patients showed decreasing transaminases and five patients died of tumor progress. In three patients, it remains unclear whether liver injury by immune checkpoint inhibitors may have ultimately contributed to the fatal course, especially in one patient with liver cirrhosis and hepatocellular carcinoma. Therapy with immune checkpoint inhibitors may lead to potentially fatal immune phenomena in susceptible patients, which may affect liver and/or other organs independently. Other causes of hepatopathy need to be ruled out clinically and/or histologically.


Phencyclidine affects firing activity of ventral tegmental area neurons that are related to reward and social behaviors in rats.
Patients with schizophrenia exhibit deficits in motivation and affect, which suggests an impairment in the reward system. The psychotomimetic drug, phencyclidine (PCP), also induces schizophrenia-like negative symptoms, such as reduced motivation, blunted affect, and social withdrawal in both humans and animals. Previous studies have indicated that the dopaminergic neurons in the ventral tegmental area (VTA) play a pivotal role in the development of reward-associated learning and motivation. However, how PCP affects the activity of VTA neurons during performance of a reward-related task and social interaction with others in unanesthetized animals remains unclear. Here, we recorded the unit activity of VTA neurons in freely moving rats before and after systemic administration of PCP in a classical conditioning paradigm, and during social interaction with an unfamiliar partner. In the classical conditioning task, two different tones were sequentially presented, one of which accompanied electrical stimulation of the medial forebrain bundle as an unconditioned stimulus. After identifying the response properties of recorded neurons in the classical conditioning task and social interaction, animals received an intraperitoneal injection of PCP. Our study demonstrated that most VTA neurons responsive to reward-associated stimuli were also activated during social interaction. Such activation of neurons was considerably suppressed by systemic administration of PCP, thus, PCP may affect the firing activity of VTA neurons that are involved in motivation, learning, and social interaction. Disruption of the response of VTA neurons to reward stimuli and socially interactive situations may be involved in PCP-induced impairments similar to the negative symptoms of schizophrenia.


F-18 FDG PET/CT evaluation of sacrococcygeal chordoma.
Chordoma is a rare malignant bone tumor derived from notochordal rests, and the most common site is the sacrococcygeal region. A 52-year-old woman presented with a sacrococcygeal chordoma detected on F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). The F-18 FDG PET/CT showed a large destructive mass that arose anteriorly in the sacrococcygeal region and heterogeneously increased FDG uptake within the mass was observed. After surgery, histology confirmed the presence of a sacrococcygeal chordoma. The physician should take chordoma into consideration if there is a large osteolytic mass with hypermetabolism in the sacral region on FDG PET/CT.


Comparative effects of glucose and water drinks on blood pressure and cardiac function in older subjects with and without postprandial hypotension.
Postprandial hypotension (PPH) occurs frequently and is thought to reflect an inadequate increase in cardiac output to compensate for the rise in splanchnic blood flow after a meal. Gastric distension by water attenuates the postprandial fall in blood pressure (BP). Cardiac hemodynamics (stroke volume (SV), cardiac output (CO), and global longitudinal strain (GLS)) have hitherto not been measured in PPH We sought to determine the comparative effects of water and glucose drinks on cardiac hemodynamics in healthy older subjects and individuals with PPH Eight healthy older subjects (age 71.0 ± 1.7 years) and eight subjects with PPH (age 75.5 ± 1.0 years) consumed a 300 mL drink of either water or 75 g glucose (including 150 mg 13C-acetate) in randomized order. BP and heart rate (HR) were measured using an automatic device, SV, CO, and GLS by transthoracic echocardiography and gastric emptying by measurement of 13CO2 In both groups, glucose decreased systolic BP (P < 0.001) and increased HR, SV, and CO (P < 0.05 for all). The fall in systolic BP was greater (P < 0.05), and increase in HR less (P < 0.05), in the PPH group, with no difference in SV or CO Water increased systolic BP (P < 0.05) in subjects with PPH and, in both groups, decreased HR (P < 0.05) without affecting SV, CO, or GLS In subjects with PPH, the hypotensive response to glucose and the pressor response to water were related (R = -0.75, P < 0.05). These observations indicate that, in PPH, the hypotensive response to oral glucose is associated with inadequate compensatory increases in CO and HR, whereas the pressor response to water ingestion is maintained and, possibly, exaggerated.


Minimally invasive digital implant-prosthetic procedure in "all on 4" rehabilitation in patients with special needs: a three-year follow-up.
The present study describes an innovative procedure for resolving implant-prosthetic cases in patients with edentulous special needs. In 2017 a 56-year-old female patient came to the Department of Dentistry of Vita-Salute San Raffaele Hospital, Milan, Italy, requiring implant-prosthetic rehabilitation of the dental arches given the difficulty in wearing removable prostheses. The first level radiological examinations were evaluated, two technical photographs were taken with specific reference, the 2D Digital Smile Design (Smile Design) was then carried out, the provisional prosthesis was performed and the CBCT requested with repere and provisional prostheses to realize the computerized implant project and an atraumatic flapless guided surgery. Professional oral hygiene sessions were performed quarterly, and the 3-year follow-up revealed no complications affecting the prosthetic or implant component. We can therefore conclude that the proposed method, exploiting digital technologies and flows and minimally invasive flapless surgical methods, can be considered elective in the treatment of patients with special needs.


[Sex behavior and reproduction of farm animals].
The sexual behaviour of farm animals was followed up both at loose-pasture raising and under industrial conditions. It was studied in estrus, in the search for a sexual partner, with regard to the tolerance of the female animals for the males in the sexual act, with regard to the herd hierarchy, the intraspecies relationships, and the condition of dominance, aggressiveness, and subordination. The role is stated of the presence of male animals in the herd for the regular course of the sexual cycle, and the shortening and synchronization of the estrus. Discussed is also the importance of the artificial visual, sound, olfactory, tactile and other stimuli of the behaviour of the male breeding animals in substantiating the coitus and the proper semen production. It was found that the reproductive process is largely dependent on on the sexual reactions of the animals, which requires a proper knowledge with regard to the substantiation of each sexual cycle. Thus, it is stated, higher conception and fertility rates are to be expected. It was also established that under the conditions of industrial technologies of raising the number of behavioural reactions in their use was strongly reduced because of the lowered contact between the individual groups, while the practice of artificial insemination thoroughly rules out the contact between the male and female animals.


Bilateral Cavernous Sinus Thrombosis as First Manifestation of Primary Burkitt Lymphoma of the Thyroid Gland.
Cavernous sinus thrombosis (CST) is a rare condition that is usually associated with infections, pregnancy, vasculitis and some types of medication, such as the contraceptive pill and paraneoplastic. Primary Burkitt lymphoma (PBL) of the thyroid gland is very uncommon and the clinical description of such cases has been largely limited to case reports. In this paper, we present a case of CST as the first manifestation of PBL of the thyroid gland. To the best of our knowledge, our patient is the first case report of PBL of the thyroid gland that presents with bilateral CST.


Acetazolamide prevents hypoxic pulmonary vasoconstriction in conscious dogs.
Acute hypoxia increases pulmonary arterial pressure and vascular resistance. Previous studies in isolated smooth muscle and perfused lungs have shown that carbonic anhydrase (CA) inhibition reduces the speed and magnitude of hypoxic pulmonary vasoconstriction (HPV). We studied whether CA inhibition by acetazolamide (Acz) is able to prevent HPV in the unanesthetized animal. Ten chronically tracheotomized, conscious dogs were investigated in three protocols. In all protocols, the dogs breathed 21% O(2) for the first hour and then 8 or 10% O(2) for the next 4 h spontaneously via a ventilator circuit. The protocols were as follows: protocol 1: controls given no Acz, inspired O(2) fraction (Fi(O(2))) = 0.10; protocol 2: Acz infused intravenously (250-mg bolus, followed by 167 microg.kg(-1).min(-1) continuously), Fi(O(2)) = 0.10; protocol 3: Acz given as above, but with Fi(O(2)) reduced to 0.08 to match the arterial Po(2) (Pa(O(2))) observed during hypoxia in controls. Pa(O(2)) was 37 Torr during hypoxia in controls, mean pulmonary arterial pressure increased from 17 +/- 1 to 23 +/- 1 mmHg, and pulmonary vascular resistance increased from 464 +/- 26 to 679 +/- 40 dyn.s(-1).cm(-5) (P < 0.05). In both Acz groups, mean pulmonary arterial pressure was 15 +/- 1 mmHg, and pulmonary vascular resistance ranged between 420 and 440 dyn.s(-1).cm(-5). These values did not change during hypoxia. In dogs given Acz at 10% O(2), the arterial Pa(O(2)) was 50 Torr owing to hyperventilation, whereas in those breathing 8% O(2) the Pa(O(2)) was 37 Torr, equivalent to controls. In conclusion, Acz prevents HPV in conscious spontaneously breathing dogs. The effect is not due to Acz-induced hyperventilation and higher alveolar Po(2), nor to changes in plasma endothelin-1, angiotensin-II, or potassium, and HPV suppression occurs despite the systemic acidosis with CA inhibition.


Neuropsychological measurement of inhibitory control in posttraumatic stress disorder: An exploratory antisaccade paradigm.
The aim of the study was to uncover inhibitory control dynamics and assess antisaccade eye-tracking tasks for relevance in a veteran posttraumatic stress disorder (PTSD) population. Participants were 36 veterans enrolled at the Washington DC Veterans Affairs Medical Center. The groups (PTSD diagnosed vs. controls) did not vary between age and sex. Participants completed a testing battery of clinical neuropsychological measures and two different eye-tracking conditions, one that utilized face stimuli and one with standard shape stimuli, which test pro- (PS) and antisaccade (AS) eye movements. Veterans with PTSD, t(33) = 2.2, p = .04, took longer to respond than controls in the standard condition AS. In the face condition, a group by task interaction was seen with increased latency for PTSD veterans in the AS versus PS task, F(3, 33) = 3.99, p = .05, with a large overall effect (Hedges' g = 1.18, p < .001) compared to controls. After controlling for depression, analyses suggested that only the face condition AS task significantly predicted dimensions of PTSD symptomology measured by the Clinician Administered PTSD Scale (CAPS) for veterans with PTSD. This is the first study to extend AS findings to PTSD and suggests a specific capability to measure inhibitory control using eye-tracking technology. We discuss the notion that reduced capacity to regulate facial-related processing affects cognitive and attentional control networks of PTSD patients, potentially representing a core cognitive deficit.


An unusual case of bilateral anterior uveitis related to moxifloxacin: the first report in Latin America.
Objective: To report a case of bilateral anterior uveitis secondary to oral moxifloxacin. Methods: Case report. Results: A 54-year-old female presented bilateral anterior uveitis following a 10-day course of oral moxifloxacin. She developed a bilateral anterior uveitis associated with pigment dispersion syndrome and iris transillumination. Conclusions: Drug-induced uveitis is one of the causes of anterior uveitis. Uveitis related to fluoroquinolones is a rare entity, there are few cases reported in the literature, this is the first case reported in Latin America.


Comparison of the three strategies of verbal scoring of the Glasgow Coma Scale in patients with stroke.
Presence of aphasia in patients with stroke poses a problem in the use of the full form (eye-motor-verbal) Glasgow Coma Scale (GCS). Stroke investigators and clinicians have used three different strategies to deal with the untestable verbal subscale, i.e. eliminating the verbal subscale; pseudoscoring with 'one', and median value substitution; but the predictive accuracy of the strategies has not been compared. To compare the predictive accuracy of the three strategies for acute mortality in stroke, we prospectively applied the GCS to 275 consecutive patients with acute stroke and recorded their survival status before discharge from hospital. 95 (33.8%) patients died. 32 (12%) patients had untestable verbal score. Receiver-Operator-Characteristic curves for predicting mortality were constructed with the GCS sum score and with the multivariate logistic models, and areas under the curves were measured to compare the predictive accuracy. They were all found to be similar (0.87-0.88 sq unit). Specifically, the GCS with eye and motor subscale had 87% accuracy compared to 88% for the model with eye, motor and verbal scale. We conclude that the short-form (eye-motor) GCS is as good a predictor of early mortality (within 2 weeks) as the full form (eye-motor-verbal) GCS in patients with stroke.


Association between the dietary inflammatory index and all-cause mortality in colorectal cancer long-term survivors.
Pro-inflammatory dietary factors have been shown to be associated with the incidence of a range of cancers. However, there are many fewer studies on the association between the inflammatory potential of diet and survival after cancer diagnosis. We examined the association between post-diagnosis dietary inflammatory index (DII®) scores and all-cause mortality in long-term survivors of colorectal cancer (CRC). DII scores were calculated from dietary data of 1,404 CRC survivors collected at a median of 6 years after CRC diagnosis. Using multivariable-adjusted Cox proportional hazards regression models, hazard ratios (HR) and 95% confidence intervals (CI) were estimated for the association of DII scores, modeled continuous and in quartiles, with all-cause mortality. After a median follow-up time of 7 years (after dietary assessment), 204 study participants had died. Overall, in the fully adjusted model there was a suggestion of a positive association between DII score and all-cause mortality (HRDIIquartile4vs1 : 1.36; 95% CI: 0.88-2.09 and HRDIIcontinuous : 1.08; 95% CI: 0.97-1.20). However, in subgroup analyses, we found significant differences in individuals with metastatic disease (HRDIIcontinuous : 1.34; 95% CI: 1.07-1.67) and the absence of stoma (HRDIIcontinuous : 1.15; 95% CI: 1.02-1.29). Overall, the post-diagnosis DII was not statistically significantly associated with all-cause mortality in CRC long-term survivors; however, there was suggestive evidence of an association in select subgroups.


Niels thorkild Rovsing: the surgeon behind the sign.
Niels Thorkild Rovsing (1862 to 1927) was a Danish surgeon. His eponyms include the Rovsing sign of acute appendicitis, the Rovsing syndrome (abdominal pain in a horseshoe kidney), the Rovsing operation I (for polycystic kidney), and the Rovsing operation II (to separate a fused "horseshoe" kidney). He received his M.D. degree in 1885 and his Ph.D. in 1889 from Copenhagen University. Rovsing practiced surgery from 1892 to 1902 at the Queen Louise Children's Hospital and the Red Cross Hospital, both located in Copenhagen. He became Professor of Surgery in 1899 and Director of Surgery at the Royal Frederiks Hospital in 1904. Rovsing earned international recognition for his innovative urological surgery. Together with his colleague, Eilert A. Tscherning, Rovsing founded the Danish Surgical Society (Dansk Kirurgisk Selskap) in 1908. His advocacy for antisepsis and Listerism advanced his notoriety and exemplified his medical leadership. His clarion call for a modern hospital led to the construction of the Copenhagen University Hospital (Rigshospitalet) that opened in 1910. Rovsing was an Honorary Member of the Edinburgh Medico-Chirurgical Society and the Association of Surgeons of Great Britain and Ireland. Rovsing served briefly as Denmark's Minister of Education in 1920. He died in 1927 from cardiac failure and laryngeal cancer.


[Retinopathy of prematurity in extremely low birth weight infants: a Tokyo multicenter study].
To investigate how the increase in survival rate in extremely low birth weight (a birth weight of 1,000 g or less) infants had affected the incidence of retinopathy of prematurity (ROP) and the frequency of laser treatment. We retrospectively reviewed the medical records of 122 surviving premature infants with birthweights less than 1,000 g to determine the severity of ROP observed at 16 neonatal intensive care units in Tokyo between April and October 2002. The survival rate was 85.6%. The mean gestational age was 26.74 weeks and the mean birth weight was 782.25 g. One-hundred-and-five infants (86.1%) developed ROP, fifty (41.0%) received laser treatment, and six (4.9%) had retinal detachment. The median postmenstrual age (gestational age at birth plus chronological age in weeks, PMA) at the onset of ROP was 32.5 weeks, and the first laser treatment was performed at the median PMA of 35.7 weeks. In these extremely low birth weight infants, there was an increase in the survival rate and in the incidence of severe ROP that progressed to the stage that required treatment.


[Validation by Rasch analysis of the Mania Scale (EMUN) for measuring manic symptions].
The Mania Scale (EMUN) developed at the Universidad Nacional de Colombia was designed to measure the severity of manic symptoms, but has been validated only using classical psychometric theory. The psychometric properties and measuring characteristics of the EMUN scale were determined using an analysis based on item response theory. Two hundred sixty-four patients with manic, hypomanic or mixed episode symptoms were assessed using the EMUN scale. The psychometric characteristics of the scale were analyzed using a Rasch model for partial credit scoring. The analysis based on the item response theory showed that reliability and separation indexes for persons are low in contrast to items. This suggested a narrow representation of the construct evaluated in this sample. Reduced need to sleep has been the most easily detectable symptom in mania. Excepting depressive affect and distractibility, the majority of items fit the model's expectation The rating scale diagnostics showed that the average measures increase monotonically across the rating scale. Two items showed redundancy and can be omitted in future versions of the scale. The person-item map suggested that the syndrome is not fully evaluated by the scale, probably because some depressive symptoms are not included. In this first study to use Rasch analysis to assess the psychometric properties of the EMUN scale, misfit and redundancy of items have been detected. The manic syndrome is not fully evaluated by the scale. The instrument can be improved by adding depressive symptoms.


Angiopeptin-eluting stents: observations in human vessels and pig coronary arteries.
Local drug delivery from polymer-coated coronary stents may reduce the incidence of in-stent restenosis. Angiopeptin, an inhibitor of smooth muscle cell proliferation, may reduce the clinical impact of restenosis. The objectives of this study were to characterize the release kinetics and distribution of angiopeptin-loaded phosphorylcholine (PC)-coated drug delivery (DD) BiodivYsio stents and assess their safety and efficacy at reducing neointima formation. I125-angiopeptin-loaded DD-PC-coated stents were implanted into human saphenous vein segments ex vivo, and I125 angiopeptin was detected in the medial layer at 1 hour. When implanted in pig coronary arteries, I125 angiopeptin was found adjacent to the stent at intervals up to 28 days. No significant amounts were found elsewhere. To assess efficacy, twelve angiopeptin-loaded DD-PC-coated stents, twelve non-loaded DD-PC stents, ten standard PC-coated stents and 8 uncoated stents were implanted into normal porcine coronary arteries. Stents were harvested at 28 days and neointima formation was assessed by computerized morphometry. No adverse tissue reactions were seen with any of the PC-coated stents. No significant differences were seen in neointimal or luminal cross-sectional areas between study groups. Local delivery of I125 angiopeptin into the vascular wall can be achieved using a PC-coated stent. Delivery of angiopeptin from drug delivery PC-coated stents is safe, but does not lead to a significant reduction in neointimal growth at 28 days within the parameters of this study.


[Imaging of the lower limb arteries: when, how and why?].
Noninvasive screening of lower limb arterial disease has long been performed using color Doppler ultrasonography, whereas surgical or endovascular treatment planning relied on conventional angiography. With continued improvements of noninvasive imaging modalities, it is now possible to image the entire lower limb vasculature without arterial catheterization. Multidetector row helical CT angiography has the advantage of visualizing the arterial lumen and arterial wall calcifications, and nephrotoxicity is reduced by decreasing amounts of contrast medium. Three-dimensional MR angiography is a safe procedure, with high contrast sensitivity, and has recently benefited from step table technology that allows a single injection of contrast medium. The literature shows that both helical CT and MR angiography have high levels of accuracy, but outcome studies of their respective role in the setting of acute and chronic lower limb ischemia are lacking. These noninvasive techniques should play a major role in two main situations: first, in critical ischemia where therapeutic planning should ideally be achieved non invasively; second, in the follow-up of treated patients presenting with recurrent ischemia.


Critical Role of Computer Simulations in Drug Discovery and Development.
The last couple of decades has witnessed that an amalgamation of multidisciplinary branches of science come together in the form of 'Bioinformatics' and made a substantial impact on the drug designing process. The applicability of Bioinformatics approaches has been able to lower down the overall cost and time of drug discovery and development. The Computer Aided Drug Designing System (CADDS) using extensive applicability of Bioinformatics has been recognized as one step ahead to carry out the primary high throughput virtual screening as an economically viable solution to the problem. The present article discusses the applicability of various Bioinformatics tools for virtual screening and molecular dynamics of selected molecules/ active ingredients derived from herbs, semi-synthetic and synthetic compounds, to predict their possible therapeutic interventions in diabetes induced neuropathy and neurodegenerative disorders. The article ends by summarizing the application of the virtual screening, lead optimization and predictions of bioavailability and bioactivity in the experimental drug development research.


Epilepsy and stigma: an update and critical review.
This article discusses the concept of illness-related stigma and its relevance to consideration of the psychosocial impact of epilepsy. It provides an overview of the recent literature on epilepsy-related stigma as it relates to the stigma experience of people with epilepsy themselves and to the beliefs and attitudes held by other key target groups. The limitations of these and previous studies are considered, and some advances in knowledge arising from them are highlighted. Finally, some suggestions are made about possible areas for further investigation.


Short term apoptotic activity of intravitreal bevacizumab on rabbit retina.
To evaluate the safety and the short term apoptotic activity of intravitreal bevacizumab in rabbit eyes by histopathological analysis. Twenty-eight eyes of 14 rabbits were divided into three groups: 8 rabbits in group 1 and 3 rabbits in each of group 2 and group 3. Intravitreal bevacizumab (1.25mg/0.05mL) was applied to the right eyes of each subject in group 1 and group 2 (11 eyes) and the same volume of saline was applied to the left eyes of each subject in group 1 and group 3 (11 eyes). The left eyes in group 2 and the right eyes in group 3 were left untreated and used as control. Enucleated eyes were used for histopathologic analyses. After immunohistochemical staining with caspase-3 and p53, there was no histological evidence of toxicity to the retina and the optic nerve in any of the sections that were analyzed in all three groups. In addition, vascular endothelial cells located at the retina and the optic nerve tissues in all groups showed a similar staining pattern with caspase-3 and p53. Our study showed that intravitreal bevacizumab with the dose of 1.25mg/0.05mL caused no histological signs of toxicity or apoptotic activity on the rabbit retina.


Retina and the tubercle Bacillus: Four decades of our journey and current understanding.
Tuberculosis continues to be a major pandemic with enormous public health implication. Involvement of ocular tissues in the form of tubercles, tuberculomas, panophthalmitis, and iris granulomas are well recognized as definitive manifestations of tuberculosis. For these lesions, confirmatory evidence is available in the form of demonstration of acid-fast Bacillus on Ziehl-Neelsen staining. For other retinochoroidal disorders such as central serous chorioretinopathy, retinal vasculitis, and presumed ocular tuberculosis, hard evidence about the role of Mycobacterium tuberculosis is lacking. In this review, work done at our center over the past four decades in the form of experimental animal studies, nucleic acid amplification assays and clinical studies regarding the above retinochoroidal pathologies and the tubercle Bacillus is presented. It is possible that revisiting experimental animal studies may be a way forward in the current scenario of ambiguity about the cause-effect relationship between M. tuberculosis and few of the retinochoroidal disorders.


Cardiac Imaging of Acute Myocarditis Following COVID-19 mRNA Vaccination.
Increasing rates of coronavirus disease 2019 (COVID-19) vaccination coverage will result in more vaccine-related side effects, including acute myocarditis. In Korea, we present a 24-year-old male with acute myocarditis following COVID-19 vaccination (BNT162b2). His chest pain developed the day after vaccination and cardiac biomarkers were elevated. Echocardiography showed minimal pericardial effusion but normal myocardial contractility. Electrocardiography revealed diffuse ST elevation in lead II, and V2-5. Cardiac magnetic resonance images showed the high signal intensity of T2- short tau inversion recovery image, the high value of T2 mapping sequence, and late gadolinium enhancement in basal inferior and inferolateral wall. It was presumed that COVID-19 mRNA vaccination was probably responsible for acute myocarditis. Clinical course of the patient was favorable and he was discharged without any adverse event.


NF-κB Blockade in Hypothalamic Paraventricular Nucleus Inhibits High-Salt-Induced Hypertension Through NLRP3 and Caspase-1.
High-salt-induced inflammation and oxidative stress in the hypothalamic paraventricular nucleus (PVN) contribute to the pathogenesis of salt-sensitive hypertension. In this study, we hypothesized that chronic inhibition of nuclear factor-κB (NF-κB) activity in the PVN delays the progression of hypertension by upregulating anti-inflammatory cytokines, reducing NLRP3 (NOD-like receptor family pyrin domain containing 3) and IL-1β and attenuating p-IKKβ, NF-κB p65 activity and NAD(P)H oxidase in the PVN of salt-sensitive hypertensive rats. Dahl salt-sensitive rats received a high-salt diet (HS, 8 % NaCl) or a normal-salt diet (NS, 0.3 % NaCl) for 6 weeks and were treated with bilateral PVN infusion with either vehicle or pyrrolidine dithiocarbamate (PDTC, 5 μg/h), a NF-κB inhibitor via osmotic minipump. The mean arterial pressure and plasma levels of norepinephrine (NE) and epinephrine (EPI) were significantly increased in high-salt-fed rats. In addition, rats with high-salt diet had higher levels of p-IKKβ, NF-κB p65 activity, Fra-like (Fra-LI) activity (an indicator of chronic neuronal activation), NOX-4 (subunits of NAD(P)H oxidase), NLRP3 and IL-1β, and lower levels of IL-10 in the PVN than normal diet rats. Bilateral PVN infusions of PDTC attenuated these high-salt-induced changes. These findings suggest that high-salt-induced NF-κB activation in the PVN caused hypertension via sympathoexcitation, which are associated with the increases of NLRP3, IL-1β and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates NLRP3, IL-1β and oxidative stress in the PVN and thereby attenuates hypertension.


Use of transgenic mouse lacI/Z mutation assays in genetic toxicology.
The Big Blue (lacI) and the Muta Mouse (lacZ/GalE) assays offer a practical means to generate mutation data from a wide range of tissues of treated animals. Our experience with these assays has so far been encouraging, but several fundamental questions require addressing. Chief among these is whether these assays are to be regarded as replacements for standard rodent genotoxicity assays, or if they are to be regarded as assays for the prediction of potential carcinogenic organotropy using a multiple-dose protocol. The interplay between the independent chemical properties of mitogenesis and DNA adduction require also to be studied. The value and sensitivity of these assays can only be assessed when these questions have been internationally addressed and concluded.


Homozygous sequence variants in the WNT10B gene underlie split hand/foot malformation.
Split-hand/split-foot malformation (SHFM), also known as ectrodactyly is a rare genetic disorder. It is a clinically and genetically heterogeneous group of limb malformations characterized by absence/hypoplasia and/or median cleft of hands and/or feet. To date, seven genes underlying SHFM have been identified. This study described four consanguineous families (A-D) segregating SHFM in an autosomal recessive manner. Linkage in the families was established to chromosome 12p11.1-q13.13 harboring WNT10B gene. Sequence analysis identified a novel homozygous nonsense variant (p.Gln154*) in exon 4 of the WNT10B gene in two families (A and B). In the other two families (C and D), a previously reported variant (c.300_306dupAGGGCGG; p.Leu103Argfs*53) was detected. This study further expands the spectrum of the sequence variants reported in the WNT10B gene, which result in the split hand/foot malformation.


Modeling of Flame Retardants in Typical Urban Indoor Environments in China during 2010-2030: Influence of Policy and Decoration and Implications for Human Exposure.
Novel flame retardants (FRs) are of increasing concern, given growing evidence of health effects and use to replace polybrominated diphenyl ethers (PBDEs). This study modeled combined effects of use policies and decoration on indoor FRs and human exposure for 18 widely used PBDEs, organophosphate esters (OPEs), and novel brominated flame retardants in typical urban indoor environments in China. The current estimated indoor emission rates and average concentrations in air and dust of the 18 FRs were 102-103 ng/h, 561 ng/m3, and 1.5 × 104 ng/g, respectively, with seven OPEs dominant (>69%). Different use patterns exist between China and the US and Europe. Scenarios modeled over 2010-2030 suggested that decoration would affect indoor concentrations of FRs more than use policies, and use policies were mainly responsible for shifts of FR composition. Additional use of hexabromobenzene and 2,3,4,5,6-pentabromotoluene and removal of BDE-209 would make the total human exposure to the modeled FR mixture increase after the restriction of penta- and octa-BDE but decrease after deca-BDE was banned. Better knowledge of the toxicity of substitutes is needed for a complete understanding of the health implications of such changes. Toddlers may be more affected by use changes than adults. Such studies are supportive to the management of FR use.


Induction of matrix metalloproteinases (MMP3, MMP12 and MMP13) expression in the microglia by amyloid-beta stimulation via the PI3K/Akt pathway.
Alzheimer's disease is characterized by the presence of senile plaques in the brain composed primarily of amyloid-beta peptide. Microglia have been reported to surround these Abeta plaques, which have opposite roles, provoking a microglia-mediated inflammatory response that contributes to neuronal cell loss or the removal of Abeta and damaged neurons. We herein analyzed the process of expression of Matrix metalloproteinases induced by Abeta stimulation. We found that Abeta1-42 induces a high level of MMP3, MMP12 and MMP13 in the microglia. The signal transduction pathway for the expression of these MMPs mRNA induced by Abeta1-42 depends on PI3K/Akt.


Dynamics of inorganic components in lake waters from Terra Nova Bay, Antarctica.
Water and Suspended Particulate Material (SPM) samples analysed in this work were collected in the austral summer 2011/12 from six shallow Antarctic lakes (Carezza, Edmonson Point 14 and 15a, Gondwana, Inexpressible Island 10b and Tarn Flat 20) of Terra Nova Bay (Northern Victoria Land, Antarctica). The total concentrations of a large suite of inorganic analytes were determined, in order to gain insight into the natural processes regulating species distribution, define natural background values and detect possible present or future local and/or global anthropogenic contamination. Lake water composition was found to be influenced by marine spray, lake geographical position and meltwater input. Seasonal variability was also evaluated for each analyte, and explained considering the natural transport processes involving each species. Multivariate chemometric techniques were used in order to identify groups of samples with similar characteristics and find out similarities and correlations among variables. The variability observed within the water samples is closely connected to the marine aerosol input; hence, it is primarily a consequence of geographical and meteorological factors, such as distance from the ocean and period of year. Higher element concentrations have been found in SPM than in water, suggesting that weathering plays an important role on the chemistry of these lakes or that adsorption processes take place. SPM samples were also examined with a Scanning Electron Microscope (SEM), and many diatoms belonging to different species were detected. No clear evidence of a relevant metal contamination was found in the investigated area.


Synergic effects of levamlodipine and bisoprolol on blood pressure reduction and organ protection in spontaneously hypertensive rats.
Stroke is a major cause of disability and death worldwide. Hypertension is one of the most important risk factors for stroke. The objective of this work was to study the synergic effects of levamlodipine and bisoprolol on blood pressure reduction and organ protection in spontaneously hypertensive rats (SHR). Blood pressure was continuously monitored in conscious SHR. For acute study, a single dose of drugs was administrated via an intragastric catheter. For chronic study (4 months), drugs were delivered via rat chow. A single dose of levamlodipine (from 1 mg/kg), bisoprolol (from 0.125 mg/kg), and their combinations significantly decreased blood pressure. The levamlodipine-induced tachycardia and the bisoprolol-induced bradycardia were temporized by the combination of these two drugs. Upon chronic treatment, this combination also decreased blood pressure variability and reduced organ damage. Levamlodipine and bisoprolol produce synergic effects on blood pressure reduction and organ protection in SHR.


Changes in root canal microbiota during the development of rat periapical lesions.
Periapical lesions are reproducibly induced in rats by pulp exposure and infection from the oral cavity. Lesions expand rapidly between day 7 and day 15-20 (active phase), with slowed expansion thereafter. In the present study we characterized the root canal microbiota present during the active phase of lesion development in this system. The mandibular first molars of Sprague-Dawley rats were exposed on day 0. The teeth were extracted after 7 days (n = 10 animals) and 15 days (n = 10), and the microbiota present in roots was isolated and characterized. The number of colonies isolated per tooth was similar on day 7 (1.53 +/- 0.64 colony-forming units x 10(3)) and day 15 (1.49 +/- 0.37 colony-forming units x 10(3)). No colonies were isolated from unexposed control teeth. Anaerobic bacteria increased significantly between day 7 (24.3 +/- 5.7%) and day 15 (47.3 +/- 7.5%), and the proportion of gram-negative organisms increased from day 7 (24.3 +/- 6.1) to day 15 (46.9 +/- 6.8). The predominant bacteria included, on day 7: Streptococcus and Bacteroides species; on day 15: species of Streptococcus, Bacteroides, Prevotella, Neisseria and Peptostreptococcus. Streptococcus oralis, Streptococcus mitis, Streptococcus rattus, Bacteroides pneumosintes and Bacteroides ureolyticus were frequently isolated at both points. Although approximately the same mean number of different species (approximately 3.5) was isolated per tooth on both day 7 and 15, the overall diversity of the isolates increased on day 15.(ABSTRACT TRUNCATED AT 250 WORDS)


Review of the postbaccalaureate degree for professional entry into physical therapy.
The American Physical Therapy Association has endorsed the postbaccalaureate entry-level degree for the physical therapy profession. This article reviews the purpose of entry-level professional training and contrasts various options of educational systems with degree structures. Professional economic, political, and educational factors are considered. After analysis of these variables, the Master of Physical Therapy degree is my recommendation for the postbaccalaureate entry-level degree for physical therapists.


Small RNAs detected in exosomes derived from the MH7A synovial fibroblast cell line with TNF-α stimulation.
Rheumatoid arthritis (RA) is an autoimmune disease that causes the chronic inflammation of the joints. Intercellular communication containing synovial fibroblasts seems to play a major role in RA pathogenesis. In this study, to better understand intercellular communication related to RA pathogenesis, we identified exosomal microRNAs (miRNAs) derived from synovial fibroblasts. Exosomes were collected from an RA synovial fibroblast (RASF) cell line, namely, MH7A, with or without stimulation by tumor necrosis factor alpha (TNF-α). We used small RNA sequencing to analyze the profile of small RNAs, including miRNAs, in MH7A exosomes and cells. By using differential expression analysis, we identified four miRNAs (miR-155-5p, miR-146a-5p, miR-323a-5p, and miR-1307-3p) that are upregulated in exosomes with TNF-α stimulation. The identification of miR-155-5p and miR-146a-5p which have been reported in RA patients demonstrated the validity of our experimental model. Other two miRNAs were newly identified. miR-323a-5p was predicted to target the protein encoding gene CD6, which attenuates T-cell activation signals, and miR-1307-3p was predicted to target the protein encoding gene N-myc downstream-regulated gene 2 (NDRG2), which inhibits osteoclast-related gene expression. The results suggested that these miRNAs might be involved in RA pathogenesis. We hope our results will help us understand the role of RASF exosomes in RA pathogenesis.


Causes of visual acuity loss among HIV-infected patients with cytomegalovirus retinitis in the era of highly active antiretroviral therapy in Chiang Mai University Hospital.
To quantify the frequencies of the common causes of visual acuity loss for HIV-infected patients with cytomegalovirus retinitis (CMVR) in the era of highly active antiretroviral therapy(HAART). The present prospective observational study comprised 113 patients (184 eyes) with newly diagnosed CMVR, from May 2008-March 2010. Each patient was followed-up every 3 months with medical history and ophthalmologic examination. Patients were divided as visual impairment and legal blindness. The majority of the patients were native Thai (91%), while the rest was of hill tribe origin. 55% were females with age ranged between 14-57 years (average of 39). The main cause of HIV infection was heterosexual contact (90%), followed by homosexual contact (7%). It was found that 68% had CD4 T-cell count less than 50 cells/microl and that 46% had bilateral CMVR. Major causes of visual impairment were CMVR zone 2&3, CMVR zone 1 and cataract, respectively. Major causes of legal blindness were CMVR zone 2&3, CMVR zone 1 and retinal detachment, respectively Retinal detachment was a major risk factor in both groups. Even when surgery was successful, the visual acuity was not significantly improved, indicating a permanent loss of vision. In the HAART era, immune recovery of HIV patients also helps restoring specific anti-CMVimmunity. HAART reduces occurrence of visual impairment to 0.10/eye-year (EY) and legal blindness to 0.15/EY, compared to the pre-HAART figures of 0.94-0.98/EY and 0.47-0.49/EY respectively. However, it did not completely eliminate the occurrence. CMVR and cataract remain the most common causes of visual acuity loss followed by retinitis-related retinal detachment, and optic nerve atrophy respectively.


Anaesthetic implications of Robinow syndrome.
Robinow (fetal face) syndrome is a rare inherited multisystem disorder featuring mesomelic or acromesomelic limb shortening, facial and spinal deformities, hypoplastic genitalia, kidney disease and congenital heart defects. We report the anaesthetic management of a patient with Robinow syndrome presenting for elective surgery and review specific issues of interest in the perioperative workup.


Expedited permanency planning: evaluation of the Kentucky Adoptions Opportunities Project.
This article presents the evaluation findings of a Kentucky Adoptions Opportunities Project (KAOP), a three-year project funded by the U.S. Department of Health and Human Services, Administration on Children, Youth and Families, Children's Bureau. The primary goal of the KAOP was implementation of three permanency planning activities: (1) risk assessment/concurrent planning, (2) one child/one legal voice, and (3) early placement in kinship or foster/adoptive homes. These activities were designed to expedite a permanency placement decision within 12 months for high-risk children. The evaluation of 124 high-risk children in the KAOP revealed that the majority of children had one or both parents coping with multiple risk factors, including mental illness, substance abuse, mental retardation, or family violence. The major barriers to permanency are discussed, as well as the policy and practice implications in the context of Adoption and Safe Families Act of 1997.


Dysregulation of the HOTAIR-miR-152-CAMKIIα Axis in Craniosynostosis Results in Impaired Osteoclast Differentiation.
Craniosynostosis is one of the most common craniofacial deformities demanding surgical treatment in infancy. LncRNA HOTAIR has verified its important role in osteogenesis and osteoarthritis. However, whether HOTAIR plays an essential role in the development of craniosynostosis is still unclear. In this study, we aimed to investigate the molecular role of HOTAIR in the osteoclast function and development of craniosynostosis.For osteoclast differentiation, RAW264.7 cells were induced by 50 ng/ml of RANKL and 10 ng/mL M-CSF, followed by TRAP staining. Cell proliferation and apoptosis were assayed by the CCK-8 kit and Annexin V-FITC apoptosis detection kit, respectively. The expression of HOTAIR was determined in PBMCs by qRT-PCR. Protein levels of all those involved genes were measured by Western blot assay. A luciferase reporter assay was used to determine the miRNA target validation. The HOTAIR expression in PBMCs from children with craniosynostosis was significantly downregulated. The results of cell proliferation and apoptosis assays indicated that silencing of HOTAIR could inhibit osteoclast differentiation and increase cell apoptosis. Moreover, the luciferase reporter assay revealed that the regulatory axis and HOTAIR-miR-152-CAMKIIα were the regulatory mechanisms of HOTAIR in the osteoclast function and development of craniosynostosis.In this study, our data showed that HOTAIR could promote osteoclast differentiation by binding miR-152. Furthermore, the HOTAIR/HOTAIR-miR-152-CAMKIIα axis was found to regulate osteoclast differentiation. These results indicate that the HOTAIR plays a crucial role in the development of osteoclasts.


SERT gene polymorphisms are associated with risk-taking behaviour and breeding parameters in wild great tits.
Individual differences in coping with potentially dangerous situations are affected by a combination of genetic and environmental factors. How genetic polymorphisms and behavioural variations are related to fitness is unknown. One of the candidate genes affecting a variety of behavioural processes, including impulsivity, anxiety and mood fluctuations in both humans and other vertebrates, is the serotonin transporter gene (SERT/SLC6A). The aim of this study was to assess an association between SERT genotypes and novelty-seeking and risk-taking behaviours as well as breeding parameters of great tits (Parus major) in a natural environment. We associated polymorphisms in the promoter exonic regions of the SERT gene with parental risk-taking-related behaviour and fitness traits. Our results show that: (1) risk-taking behaviour in our great tit population is linked to single nucleotide polymorphisms in the SERT gene exon 3 and exon 8; (2) the genotype-behaviour associations are consistent with the presence of different stressors; and (3) polymorphisms in exon 8 could be associated with fitness-related traits, such as the start of egg-laying and hatching success. We showed for the first time that genetic variability of SERT plays an important role in shaping individual decision-making that affects fitness in a wild population. However, the results are based on one population and on the polymorphisms that are in a single gene. Therefore, replication studies are needed in order to confirm these preliminary results.


Laparoscopic standard pelvic node dissection for carcinoma of the prostate: is it accurate?
The acceptably low morbidity of laparoscopic pelvic lymphadenectomy has allowed us to perform the procedure systematically on all patients who presented with localized adenocarcinoma of the prostate. Data on 147 consecutive cases enable us to state that the overall accuracy and morbidity of this method are equal if not better than the rates available in the literature for open procedures. In addition, analysis shows that the standard dissection is more accurate than the obturator dissection because in 30% of the patients with positive nodes malignant infiltrates were found in the iliac specimen only. Finally, it appears that patients in whom the malignancy was detected by ultrasound only may not require lymphadenectomy because in our group of 28 patients no positive nodes were detected.