Saccadic suppression of displacement in face of saccade adaptation.
Saccades challenge visual perception since they induce large shifts of the image on the retina. Nevertheless, we perceive the outer world as being stable. The saccadic system also can rapidly adapt to changes in the environment (saccadic adaptation). In such case, a dissociation is introduced between a driving visual signal (the original saccade target) and a motor output (the adapted saccade vector). The question arises, how saccadic adaptation interferes with perceptual visual stability. In order to answer this question, we engaged human subjects in a saccade adaptation paradigm and interspersed trials in which the saccade target was displaced perisaccadically to a random position. In these trials subjects had to report on their perception of displacements of the saccade target. Subjects were tested in two conditions. In the 'blank' condition, the saccade target was briefly blanked after the end of the saccade. In the 'no-blank' condition the target was permanently visible. Confirming previous findings, the visual system was rather insensitive to displacements of the saccade target in an unadapted state, an effect termed saccadic suppression of displacement (SSD). In all adaptation conditions, we found spatial perception to correlate with the adaptive changes in saccade landing site. In contrast, small changes in saccade amplitude that occurred on a trial by trial basis did not correlate with perception. In the 'no-blank' condition we observed a prominent increase in suppression strength during backward adaptation. We discuss our findings in the context of existing theories on transsaccadic perceptual stability and its neural basis.


The ontogeny of visual-motor memory and its importance in handwriting and reading: a developing construct.
Humans have evolved a remarkable ability to remember visual shapes and use these representations to generate motor activity (from Palaeolithic cave drawings through Jiahu symbols to cursive handwriting). The term visual-motor memory (VMM) describes this psychological ability, which must have conveyed an evolutionary advantage and remains critically important to humans (e.g. when learning to write). Surprisingly, little empirical investigation of this unique human ability exists--almost certainly because of the technological difficulties involved in measuring VMM. We deployed a novel technique for measuring this construct in 87 children (6-11 years old, 44 females). Children drew novel shapes presented briefly on a tablet laptop screen, drawing their responses from memory on the screen using a digitizer stylus. Sophisticated algorithms (using point-registration techniques) objectively quantified the accuracy of the children's reproductions. VMM improved with age and performance decreased with shape complexity, indicating that the measure captured meaningful developmental changes. The relationship between VMM and scores on nationally standardized writing assessments were explored with the results showing a clear relationship between these measures, even after controlling for age. Moreover, a relationship between VMM and the nationally standardized reading test was mediated via writing ability, suggesting VMM's wider importance within language development.


The carboxy-terminal tail of pyruvate dehydrogenase kinase 2 is required for the kinase activity.
Pyruvate dehydrogenase kinase 2 (PDK2) is a prototypical mitochondrial protein kinase that regulates the activity of the pyruvate dehydrogenase complex. Recent structural studies have established that PDK2 consists of a catalytic core built of the B and K domains and the relatively long amino and carboxyl tails of unknown function. Here, we show that the carboxy-terminal truncation variants of PDK2 display a greatly diminished capacity for phosphorylation of holo-PDC. This effect is due largely to the inability of the transacetylase component of PDC to promote the phosphorylation reaction catalyzed by the truncated PDK2 variants. Furthermore, the truncated forms of PDK2 bind poorly to the lipoyl-bearing domain(s) provided by the transacetylase component. Taken together, these data strongly suggest that the carboxyl tails of PDK isozymes contribute to the lipoyl-bearing domain-binding site of the kinase molecule. We also show that the carboxyl tails derived from isozymes PDK1, PDK3, and PDK4 are capable of supporting the kinase activity of the kinase core derived from PDK2 as well as binding of the respective PDK2 chimeras to the lipoyl-bearing domain. Furthermore, the chimera carrying the carboxyl tail of PDK3 displays a stronger response to the addition of the transacetylase component along with a better binding to the lipoyl-bearing domain, suggesting that, at least in part, the differences in the amino acid sequences of the carboxyl tails account for the differences between PDK isozymes.


Psychological stress exerts an adjuvant effect on skin dendritic cell functions in vivo.
Psychological stress affects the pathophysiology of infectious, inflammatory, and autoimmune diseases. However, the mechanisms by which stress could modulate immune responses in vivo are poorly understood. In this study, we report that application of a psychological stress before immunization exerts an adjuvant effect on dendritic cell (DC), resulting in increased primary and memory Ag-specific T cell immune responses. Acute stress dramatically enhanced the skin delayed-type hypersensitivity reaction to haptens, which is mediated by CD8(+) CTLs. This effect was due to increased migration of skin DCs, resulting in augmented CD8(+) T cell priming in draining lymph nodes and enhanced recruitment of CD8(+) T cell effectors in the skin upon challenge. This adjuvant effect of stress was mediated by norepinephrine (NE), but not corticosteroids, as demonstrated by normalization of the skin delayed-type hypersensitivity reaction and DC migratory properties following selective depletion of NE. These results suggest that release of NE by sympathetic nerve termini during a psychological stress exerts an adjuvant effect on DC by promoting enhanced migration to lymph nodes, resulting in increased Ag-specific T cell responses. Our findings may open new ways in the treatment of inflammatory diseases, e.g., psoriasis, allergic contact dermatitis, and atopic dermatitis.


Clinicopathologic analysis of esophageal and cardiac cancers and survey of molecular expression on tissue arrays in Chaoshan littoral of China.
To investigate clinical and pathologic data of esophageal carcinoma (EC) and cardiac carcinoma (CC) among residents in Chaoshan region of China. Clinical and pathologic data of 9 650 patients with EC and 4 173 patients with CC in the Chaoshan population were collected and analyzed. Moreover, Chaoshan esophageal carcinoma tissue arrays were made for high-throughput study. Male to female ratio was 3:1 in patients with EC and 4.75:1 in CC. The average age of the occurrence of EC was 54.6 years, and of CC was 58.1 years. For both EC and CC, age at diagnosis was a little younger in Chaoshan region than in most other areas. The most commonly affected site of esophageal carcinoma was the middle third of esophagus (72.0%); the second was the lower third (15.3%). The main gross type of esophageal carcinoma was ulcerative type (41.50%); the medullary type was the second (39.6%). Squamous cell carcinoma accounted for the overwhelming majority of esophageal cancer (96.4%); adenocarcinoma accounted for the overwhelming majority of cardiac carcinoma (94.5%). Chaoshan esophageal carcinoma tissue arrays were easily for high-throughput study, and tissue cores with a diameter of 1.5 mm could better keep more structure for molecular expression study. Both EC and CC are common in males. The average occurrence age of EC and CC is younger in Chaoshan than in most other regions of China. The most commonly affected site of esophageal carcinoma was the middle third of esophagus (72.0%). Squamous cell carcinoma accounted for the overwhelming majority of esophageal cancer; adenocarcinoma accounted for the overwhelming majority of cardiac carcinoma. Tissue arrays technology is applicable for rapid molecular profiling of large numbers of cancers in a single experiment.


The first review study on association of DNA methylation with gastric cancer in Iranian population.
Gastric cancer (GC) is the second leading cause of cancer-related death worldwide. Several environmental, genetic and epigenetic factors have been suggested to have a role in GC development. Epigenetic mechanisms like histone changes and promoter hyper-methylation are now being increasingly studied. Associations between methylation of many gene promoters with the risk of gastric cancer have been investigated worldwide. Such aberrant methylation may result in silencing of specific genes related to cell cycling, cell adhesion, apoptosis and DNA repair. Thus this molecular mechanism might have a key role in proliferation and migration of cancerous cells. In this review article we included studies conducted on DNA methylation and gastric cancer in Iranian populations. Using Science direct, Pubmed/PMC, Springer, Wiley online library and SciELO databases, all published data until 31 January 2016 were gathered. We also searched Science direct data base for similar investigations around the world to make a comparison between Iran and other countries. By searching these databases, we found that the association between methylation of seven gene promoters and gastric cancer had been studied in Iran until 31 January 2016. These genes were p16, hLMH1, E-cadherin, CTLA4, THRβ, mir9 and APC. Searching in science direct database also showed that 92 articles had been published around the world till January 2016. Our investigation revealed that despite the importance of GC and its high prevalence in Iran, the methylation status of only a few gene promoters has been studied so far. More studies with higher sample numbers are needed to reveal the relation of methylation status of gene promoters to gastric cancer in Iran. Further studies will be helpful in identifying associations of DNA methylation in candidate genes with gastric cancer risk in Iranian populations.


Case for resurgence of radical perineal prostatecomy in Indian subcontinent.
Radical perineal prostatectomy was the first surgery described for prostatic carcinoma (Young, 1904) but it lost its eminent status after Walsh's description in 1982 of anatomic radical retropubic prostatectomy followed by the enthusiasm in laparoscopy and now robotics. It made resurgence after it was realized in early 1990s that the pelvic lymph node dissection is needed only in selected cases. Last decade witnessed over 80 publications addressing the results and advances in the perineal approach. Strangely, centres from the subcontinent have chosen to ignore this resurgence. We describe our early experience with the technique in 35 patients and present the case for its more widespread usage. Thirty five patients of clinically localized carcinoma prostate were operated by perineal route in our institution from December 2006 onwards. All patients had serum prostate specific antigen levels less than 10 ng/ml. Operating time was 2 to 3.5 hours (mean 2.5 hours). Rectal injury occurred in three patients but was closed primarily in all and none required a colostomy. Mean duration of hospital stay was four days. The disease was organ confined in 25(71%). Positive margins were seen in 5(14%) patients. Biochemical recurrence occurred in 17% patients at one year. Seventy six percent patients had achieved continence at one year. As the world is taking note of radical perineal prostatectomy again, with a very small learning curve, minimal invasion and good oncological control urologists from Indian subcontinent should also embrace this procedure in view of the relative limited resources available.


Methacycline hyperpigmentation: a five-year follow-up.
A five-year follow-up is presented of a unique material of patients who acquired a greyish black hyperpigmentation during long-term methacycline therapy for chronic bronchitis. The melanosis disappeared in cases in which tetracycline therapy was discontinued during the observation period but not in those in which doxycycline had been substituted. In two autopsy cases pigment deposits were also found in cartilage and atherosclerotic lesions. Overall clinical and microscopic findings suggest a similarity to the pigmentation occurring in iatrogenic ochronosis.


Recent Progress on Electromagnetic Field Measurement Based on Optical Sensors.
Electromagnetic field sensors are widely used in various areas. In recent years, great progress has been made in the optical sensing technique for electromagnetic field measurement, and varieties of corresponding sensors have been proposed. Types of magnetic field optical sensors were presented, including probes-based Faraday effect, magnetostrictive materials, and magnetic fluid. The sensing system-based Faraday effect is complex, and the sensors are mostly used in intensive magnetic field measurement. Magnetic field optical sensors based on magnetic fluid have high sensitivity compared to that based on magnetostrictive materials. Three types of electric field optical sensors are presented, including the sensor probes based on electric-optic crystal, piezoelectric materials, and electrostatic attraction. The majority of sensors are developed using the sensing scheme of combining the LiNbO3 crystal and optical fiber interferometer due to the good electro-optic properties of the crystal. The piezoelectric materials-based electric field sensors have simple structure and easy fabrication, but it is not suitable for weak electric field measurement. The sensing principle based on electrostatic attraction is less commonly-used sensing methods. This review aims at presenting the advances in optical sensing technology for electromagnetic field measurement, analyzing the principles of different types of sensors and discussing each advantage and disadvantage, as well as the future outlook on the performance improvement of sensors.


Directed biosynthesis of peptaibol antibiotics in two Trichoderma strains. II. Structure elucidation.
Alpha-aminoisobutyric acid-directed biosynthesis in two Trichoderma strains has been shown to lead to the simplification of the natural peptaibol microheterogeneous mixtures and to the production of new analogues. Hence, two new peptides originating from T. harzianum, trichorzin PA(U) 4 and harzianin PCU 4, were isolated by HPLC. Their sequences were determined by positive liquid secondary-ion mass spectrometry (LSI MS). Trichorzin PA(U) 4 and harzianin PC(U) 4 are 18- and 14-residue peptaibols, respectively, both containing a high proportion of alpha-aminoisobutyric acid (Aib). LSI MS performed with lithium cationized peptides, allowed to assign the relative position of leucine/isoleucine isomeric residues, even without the use of tandem mass spectrometry.


Report of nine cases of accidental injury to man with Freund's complete adjuvant.
Nine cases of accidental injury with Freund's complete adjuvant to man are reported. One case is reported in detail and the other eight have been seen and reviewed retrospectively. Reactions developed in Mantoux positive individuals, who injected Freund's complete adjuvant with another protein. However, not all such injections produced the reaction. Treatment was unsuccessful, although one reaction may have been aborted by early surgical excision of the site of injection.


Psychological mediators of avoidance and endurance behavior after concussion.
The avoidance-endurance model (AEM) proposes multiple pathways from acute to chronic pain, with distinct cognitive and behavioral components in each pathway. The AEM may also be applicable to persistent symptoms after concussion. In this study, we tested the AEM as an explanatory framework for concussion outcomes, by using mediation analyses through the proposed psychological mechanisms. Based on the AEM, we hypothesized that postconcussion symptoms would significantly predict avoidance behavior through catastrophizing, and endurance behavior through thought suppression and self-distraction. We recruited 84 adults seeking treatment at 2 outpatient concussion clinics (M = 41.8 years old, 63% female) who completed measures of postconcussion symptoms, catastrophizing, thought suppression, "self-distraction" (Five Factor Mindfulness Questionnaire "Act with Awareness" Scale reverse-scored), avoidance behavior, and endurance behavior at an average of 17.8 weeks postconcussion. We conducted 3 mediation analyses to assess each of the AEM pathways. We found a significant indirect effect of postconcussion symptoms on avoidance behavior through catastrophizing (ab = .113 (.036), 95% CI [.053, .195]). The indirect effects of postconcussion symptoms on endurance behavior through thought suppression (ab = .011 (.012), 90% CI [.002, .035]) and "self-distraction" (ab = .003 (.009), 90% CI [.008, .022]) were not statistically significant. Results supported the catastrophizing-avoidance pathway in concussion, but not the thought-suppression-endurance or self-distraction-endurance pathways. Therefore, catastrophic thinking about concussion symptoms may be an appropriate treatment target for individuals who exhibit fear-avoidance behavior. Further research is needed to establish whether thought suppression and self-distraction are relevant for interventions aimed at reducing excessive endurance behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


rAAV-Mediated Overexpression of SOX9 and TGF-β via Carbon Dot-Guided Vector Delivery Enhances the Biological Activities in Human Bone Marrow-Derived Mesenchymal Stromal Cells.
Scaffold-assisted gene therapy is a highly promising tool to treat articular cartilage lesions upon direct delivery of chondrogenic candidate sequences. The goal of this study was to examine the feasibility and benefits of providing highly chondroreparative agents, the cartilage-specific sex-determining region Y-type high-mobility group 9 (SOX9) transcription factor or the transforming growth factor beta (TGF-β), to human bone marrow-derived mesenchymal stromal cells (hMSCs) via clinically adapted, independent recombinant adeno-associated virus (rAAV) vectors formulated with carbon dots (CDs), a novel class of carbon-dominated nanomaterials. Effective complexation and release of a reporter rAAV-lacZ vector was achieved using four different CDs elaborated from 1-citric acid and pentaethylenehexamine (CD-1); 2-citric acid, poly(ethylene glycol) monomethyl ether (MW 550 Da), and N,N-dimethylethylenediamine (CD-2); 3-citric acid, branched poly(ethylenimine) (MW 600 Da), and poly(ethylene glycol) monomethyl ether (MW 2 kDa) (CD-3); and 4-citric acid and branched poly(ethylenimine) (MW 600 Da) (CD-4), allowing for the genetic modification of hMSCs. Among the nanoparticles, CD-2 showed an optimal ability for rAAV delivery (up to 2.2-fold increase in lacZ expression relative to free vector treatment with 100% cell viability for at least 10 days, the longest time point examined). Administration of therapeutic (SOX9, TGF-β) rAAV vectors in hMSCs via CD-2 led to the effective overexpression of each independent transgene, promoting enhanced cell proliferation (TGF-β) and cartilage matrix deposition (glycosaminoglycans, type-II collagen) for at least 21 days relative to control treatments (CD-2 lacking rAAV or associated to rAAV-lacZ), while advantageously restricting undesirable type-I and -X collagen deposition. These results reveal the potential of CD-guided rAAV gene administration in hMSCs as safe, non-invasive systems for translational strategies to enhance cartilage repair.


Education and training to support radiation protection research in Europe: the DoReMi experience.
A review is presented to the program of education and training setup within the DoReMi Network of Excellence. DoReMi was funded by Euratom under the EU 7th Framework Programme to coordinate the EU research into risks from low-dose ionizing radiation. It was seen to be necessary to form a network of expert institutions in order to tackle the scientific questions with the resources available. From the start, importance was given to the need to stimulate and support education and training to build up the capability of the research community. DoReMi dedicated a workpackage to education and training that put in place a number of activities that have been successful in attracting new students into the area and introducing research scientists to new topic areas and technologies. The program of education and training in DoReMi provided a significant contribution to the low-dose radiation research community and has been further developed and extended in the following Euratom-funded project OPERRA and the European Joint Programme CONCERT.


Short-term infusion of LongR(3) insulin-like growth factor (IGF)-I decreases hepatic IGF-I mRNA but not IGF binding protein-3 mRNA expression in pigs.
Infusion of pigs with an insulin-like growth factor-I (IGF-I) analogue (LongR(3)IGF-I) that does not bind to IGF-binding proteins decreases growth rate and the plasma concentration of growth hormone (GH), IGF-I, IGFBP-3, and insulin. This study was designed to determine whether the decrease is due to changes in IGF-I and IGFBP-3 gene expression. IGF-I or LongR(3)IGF-I (180 microg/kg/day) was infused into 55-kg finisher pigs for 4 days using Travenol infuser pumps. Plasma IGF-I concentration was measured by radioimmunoassay and plasma IGFBP-3 and IGFBP-2 were estimated by Western ligand blotting. Steady-state levels of IGF-I and IGFBP-3 mRNA were measured by RNase protection assay. Neither IGF-I nor LongR(3)IGF-I had a significant effect on hepatic IGF-I class 1 mRNA expression, whereas hepatic IGF-I class 2 mRNA expression was significantly reduced by both peptides. Plasma IGFBP-3 levels were unaffected by IGF-I treatment but were reduced by LongR(3)IGF-I treatment. The decrease in IGFBP-3 was not due to decreased gene expression in porcine liver or kidney, since neither IGF-I nor LongR(3)IGF-I treatment altered IGFBP-3 mRNA. This study infers a direct effect of the IGF analogue LongR(3)IGF-I on GH through its inhibition of plasma IGF-I concentration and class 2 IGF-I mRNA. The decrease in plasma IGFBP-3 was not accompanied by a decrease in hepatic or renal IGFBP-3 mRNA, suggesting that in this case, plasma IGFBP-3 protein levels are posttranslationally regulated or are derived from tissues other than liver or kidney.


Evaluation of the hypocholesterolemic effect and prebiotic activity of a lentil (Lens culinaris Medik) extract.
The aim of our work was to produce a hydroalcoholic extract of lentils and to examine (a) the hypocholesterolemic action in an animal model, by studying the plasma cholesterol level and the concentration of bile acids in the feces; (b) the potential prebiotic effect, by conducting an in vitro culture fermentation experiment and assessing the level of SCFAs in the feces of rats. Lentil extract (LE) was obtained by extracting lentils with a solution of H2 0/EtOH (70/30 v/v) for 3 h, and the content of main nutrients was determined. After 71 days of diet-induced hypercholesterolemia in rats, LE reduced the cholesterol level of rats of 16.8% (p < 0.05) and increased the level of bile acids in the feces of rats (p < 0.01). LE revealed the same prebiotic activity of inulin and good bifidogenic activity, inasmuch as it enhanced the growth of Bifidobacterium spp. by 3 log (p < 0.05). The concentration of SCFAs in the feces of rats fed with LE increased during the time of the study. This new hydroalcoholic extract obtained from lentils was shown to possess hypocholesterolemic and prebiotic properties, and could have interesting applications in the field of nutraceuticals.


MiR-940 inhibits TGF-β-induced epithelial-mesenchymal transition and cell invasion by targeting Snail in non-small cell lung cancer.
Increased evidence reveals that miR-940 inhibits the migration and invasion of cancer cells. Considering transforming growth factor β (TGF-β) signaling is crucial to cellular epithelial-mesenchymal transition (EMT) process and metastasis of cancer, it is in urgent to explore whether and how miR-940 plays an essential role in regulating TGF-β-induced EMT in lung cancer progression. In the present study, we observed a reciprocal expression with down-regulated miR-940 and up-regulated Snail mRNA in non-small-cell lung cancer (NSCLC) tissues. we further found that the expression of miR-940 was decreased in NSCLC tissues with lymph node metastasis, advanced TNM stages and poor cell differentiation, in which, on the contrary, the expression of Snail was increased. Overexpression of miR-940 significantly inhibited Snail mRNA and protein expression in A549 and H226 cells. Mechanistically, Snail mRNA was identified as target of miR-940. In addition, miR-940 repressed TGF-β-induced EMT and further hampered the cell migration and invasion. Finally, siRNA-mediated knockdown of Snail copied the phenotype of miR-940 overexpression in A549 and H226 cells. Taken together, our study reveals that miR-940 can suppress TGF-β-induced EMT and cell invasion by targeting Snail 3'-UTR mRNA in NSCLC.


Surgeon Type and Outcomes After Inpatient Ankle Arthrodesis and Total Ankle Arthroplasty: A Retrospective Cohort Study Using the Nationwide Premier Healthcare Claims Database.
Two main treatments for end-stage ankle arthritis are ankle arthrodesis and total ankle arthroplasty (TAA). While both procedures can be performed either by a foot and ankle orthopaedic surgeon or a podiatrist (when within a particular state's scope of practice), studies comparing the surgical outcomes of the 2 surgeon types are lacking. Therefore, in this study, we compared outcomes by surgeon type for TAA and for ankle arthrodesis. This retrospective cohort study utilized data from the nationwide Premier Healthcare claims database (2011 to 2016) regarding TAA (n = 3,674) and ankle arthrodesis (n = 4,980) procedures. Multivariable models estimated associations between surgeon type (podiatrist versus orthopaedic foot and ankle surgeon) and opioid utilization (in oral morphine equivalents [OMEs]), length of stay, and cost of hospitalization. We report percent change (compared with reference) and 95% confidence intervals (CIs). Overall, 76.5% (n = 2,812) and 18.8% (n = 690) of TAA procedures were performed by orthopaedic foot and ankle surgeons and podiatrists, respectively; surgeon type was unknown for 4.7% (n = 172). For ankle arthrodesis, 75.3% (n = 3,752) and 18.3% (n = 912) of the procedures were performed by orthopaedic foot and ankle surgeons and podiatrists, respectively; surgeon type was unknown for 6.3% (n = 316). The proportion of TAA and ankle arthrodesis procedures performed by podiatrists increased over time, from 12.8% and 13.6% in 2011 to 24.6% and 26.0% in 2016, respectively. When adjusting for relevant covariates, procedures performed by podiatrists (compared with orthopaedic foot and ankle surgeons) were associated with increased length of stay: for TAA, +16.7% (95% CI, 7.6% to 26.5%; median, 2 days in both groups) and for ankle arthrodesis, +14.2% (95% CI, 7.9% to 20.9%; median, 3 compared with 2 days) (p < 0.05 for both). In addition, ankle arthrodesis performed by podiatrists was associated with increased cost of hospitalization: +28.5% (95% CI, 22.1% to 35.2%; median, $19,236 compared with $13,433) (p < 0.05). Differences in opioid utilization were nonsignificant in the main analysis: +10.9% (95% CI, -3.1% to 26.8%; median, 345 compared with 250 OMEs) and +2.8% (95% CI, -5.9% to 12.4%; median, 351 compared with 315 OMEs) for TAA and ankle arthrodesis, respectively. An increasing trend in the proportion of procedures performed by podiatrists was coupled with apparent increases in length of stay and cost compared with procedures performed by orthopaedic foot and ankle surgeons. Given the increasing demand for these procedures, factors associated with resource utilization, such as type of surgeon, may be increasingly important on the population level. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


[Intranasal approaches for pituitary area tumors. Our experience].
Transsphenoidal approach is the most commonly employed surgical technique for the resection of pituitary tumors. We present our experience in the transnasal-transsphenoidal approach in 30 patients undergoing pituitary surgery from 1998 to 2002. Ten patients underwent surgery via a sublabial-transeptal-transsphenoidal approach, 15 patients via a transeptal-transsphenoidal approach and 5 patients via a pure endoscopic transnasal-transsphenoidal. The pathological study showed 29 pituitary adenomas and 1 Rathe's cleft cyst. We conclude that the pure endoscopic transnasal-transsphenoidal approach guided by a navigator-system is safest and more effective approach. We reserved the transeptal-transsphenoidal approach for cases with obstructive septal deflection and poor pneumatized sphenoid sinuses. We do not recommend the use of the sublabial-trans-sphenoidal approach.


Effects of optical correction media on contrast sensitivity.
Contrast sensitivity functions (CSFs) were obtained for 257 emmetropic subjects (514 eyes) and 35 contact lens users (64 eyes) in the Republic of Singapore Air Force using the Vistech Contrast Test System. For the emmetropes, contrast sensitivity tests were carried out with and without plano spectacles (PS). For the myopes, we compared their performances with spectacles, daily-wear soft contact lenses (CLs), and CL plus PS at Snellen visual acuities of 6/6 or better. Paired t-tests showed that there were no significant differences (P > 0.05) when CSFs of the emmetropes were measured with and without PS and when that of the CL users were measured with spectacles, CL and CL plus PS. We therefore conclude that myopic optical correction media do not retard CSF significantly based on the Vistech charts, although they may reduce image size and modify light transmission by being imperfect transparencies. The observed decrease in CSF for myopes even after myopic correction might therefore be related to other factors associated with myopia, such as retinal changes or possibly mild amblyopia.


Is breast reduction in puberty indicated? Retrospective observations of patients with a local hypersensitivity of estrogen and progesterone receptors.
The authors described two women in whom at the age of 14 and 15 diagnosed was gigantomasty and a hypersensitivity of the estrogen receptor. In both the patients at that time a significant increase of the estrogen and progesterone receptors in the breast glandular tissue was ascertained. The immunohistochemical investigation shows a significant higher sensitivity of the progesterone and estrogen receptors. In both the girls observed was gigantomasty with hyperlordosis, deformities of the chest and back, skin changes, orthopnoe. In both the patients a total mastectomy was performed. Both the girls had after surgery a normal menstruation, were married with normal sexual activity. One of the patients had a normal delivery two years ago.


Optimizing therapy of seizures in children and adolescents with developmental disabilities.
Children and adolescents with intellectual and developmental disabilities and epilepsy are a unique patient population that offers significant challenges. They are more likely to suffer lifelong intractable epilepsy with multiple seizure types than other patients with epilepsy. In addition, these patients often cannot clearly express their complaints about antiepileptic drug (AED) side effects, and the caregiver's role becomes all-important as an advocate for the patient. Finally, behavioral and psychiatric comorbidities are common and need to be considered when choosing an AED in this patient population. Our society will be judged by how we care for the most unfortunate among us.


Relationship of serum uric acid to measures of endothelial function and atherosclerosis in healthy adults.
Although uric acid (UA) is considered as an antioxidant, the relationship between serum UA levels and cardiovascular diseases is not clear yet. Higher brachial artery resting diameter (BD), impaired brachial artery flow-mediated dilatation (FMD), increased carotid intima-media thickness (IMT), decreased aortic distensibility (AoD), and increased aortic stiffness index (AoSI) and elastic modulus (AoEM) are predictors for development and/or progression of atherosclerosis. In this study, BD, FMD, carotid IMT, AoD, AoSI and AoEM were studied in healthy subjects with UA concentrations in physiological range. One hundred 24 healthy volunteers between 26 and 55 years of age were included in this study. Each subject had a serum UA levels in normal range. Carotid IMT, BD and brachial FMD were measured by means of high-resolution vascular ultrasound. AoD, AoSI, AoEM were examined by transthoracic echocardiography. Endothelium-dependent dilatation (EDD) was assessed by establishing reactive hyperemia and endothelium-independent dilatation (EID) was determined by using sublingual isosorbide dinitrate. Although carotid IMT and EDD were significantly correlated with UA concentrations (r = 0.346, p < 0.0001; r = -0.255, p < 0.05, respectively), EID measurements were not significantly correlated with serum UA concentrations (r = - 0.105, p > 0.05). In addition, AoSI and AoEM were significantly correlated with serum UA levels (r = 0.368, p < 0.0001; r = -0.366, p < 0.0001, respectively), and there was a significant inverse correlation between AoD and serum UA concentrations (r = -0.366, p < 0.0001). Furthermore, in multivariate analysis, we found that serum UA concentrations were correlated with increased carotid IMT, reduced FMD and increased aortic stiffness independent of other cardiovascular risk factor (beta = 256, p = 0.002; beta = -193, p = 0.03; beta = 0.295, p < 0.0001, respectively). In healthy subjects, increased serum UA concentrations, even in physiological range, are a risk factor for increased carotid IMT, reduced FMD and increased aortic stiffness independent of other cardiovascular risk factor, and other factors related to the metabolic syndrome.


The independent contribution of executive functions to health related quality of life in older women.
Cognition is a multidimensional construct and to our knowledge, no previous studies have examined the independent contribution of specific domains of cognition to health related quality of life. To determine whether executive functions are independently associated with health related quality of life assessed using Quality Adjusted Life Years (QALYs) calculated from the EuroQol EQ-5D (EQ-5D) in older women after adjusting for known covariates, including global cognition. Therefore, we conducted a secondary analysis of community-dwelling older women aged 65-75 years who participated in a 12-month randomized controlled trial of resistance training. We assessed global cognition using the Mini-Mental State Examination (MMSE) and executive functions using the: 1) Stroop Test; 2) Trail Making Test (Part B) and 3) Digits Verbal Span Backwards Test. We calculated QALYs from the EQ-5D administered at baseline, 6 months and 12 months. Our multivariate linear regression model demonstrated the specific executive processes of set shifting and working memory, as measured by Trail Making Test (Part B) and Digits Verbal Span Backward Test (p < 0.01) respectively, were independently associated with QALYs after accounting for age, comorbidities, general mobility, and global cognition. The final model explained 50% of the variation in QALYs. Our study highlights the specific executive processes of set shifting and working memory were independently associated with QALYs -- a measure of health related quality of life. Given that executive functions explain variability in QALYs, clinicians may need to consider assessing executive functions when measuring health related quality of life. Further, the EQ-5D may be used to track changes in health status over time and serve as a screening tool for clinicians.


Neutrophil behavior following exposure to in vivo or in vitro zinc in normal and acutely-inflamed rats: studies on lysozyme secretion, superoxide anion release and platelet adhesion.
The mechanism was studied of the anti-inflammatory effect of oral zinc (114 mg/kg/day of elemental metal, given for 14 days) on the development of the carrageenan-induced paw oedema of the rat, and the impact of in vivo treatment on the activity of neutrophils isolated from the blood of inflamed and non-inflamed animals. The effects of the in vitro incubation with the metal on either non-inflamed or inflamed neutrophils coming from zinc-untreated rats were also examined. It was found that the administration of oral zinc inhibited markedly the process of ex vivo adhesion of the cells obtained from the inflamed rats (an observation confirmed by the in vitro experiments). In vitro release of lysozyme and superoxide anion productions were measured: in the absence of zinc, the 30' of pre-incubation carried out before stimulating with PMA did not influence the cell's reactivity of the non-inflamed neutrophils. It was, on the contrary, capable of significantly reducing that of the inflamed ones. As a consequence, it is quite difficult to properly interpret the data obtained studying the activity of the cells exposed to the metal in vitro.


Effect of application technique and dentin bonding agent interaction on shear bond strength.
This study evaluated the interaction of five clinical application techniques and the shear bond strength of four DBAs (OptiBond FL, Clearfil SE Bond, PQ1 and Prime & Bond NT). A hybrid resin composite (Herculite XRV restorative resin) was attached to human dentin surfaces using five application techniques: Group A--adhesive spread with a 3M brush for 30 seconds, followed by compressed air 0.5 cm from the surface for one second to remove the excess adhesive. Group B--adhesive spread with a 3M brush for 30 seconds, followed by compressed air 0.5 cm from the surface for three seconds to remove the excess adhesive. Group C--adhesive spread with 3M brush for 30 seconds, excess adhesive removed with a clean brush, two strokes side by side, no compressed air. Group D--adhesive spread with a Micro-applicator brush for 30 seconds followed by compressed air 0.5 cm from the surface for one second to remove the excess adhesive. Group E--adhesive spread with a Micro-applicator brush for 30 seconds, the excess adhesive removed with a clean brush, two strokes side by side and no compressed air. The specimens were stored in distilled water at 37 degrees C for 24 hours, followed by thermocycling between 5 degrees C and 55 degrees C for 1,000 cycles. The shear bond strengths were determined on a universal testing machine operating with a crosshead speed of 5 mm/minute. The fracture sites were examined by 20x stereo microscope to determine the type of failure that occurred during the debonding procedure. Bond strength data were compared with analysis of variance at a significance level of p<0.05. Post hoc comparisons of means were performed with t-tests with p-values adjusted for multiple comparisons. This in vitro study concluded that there was an interaction between the application technique and bonding agent tested. All DBAs utilized the one-second compressed air technique, which yielded the highest bond strengths.


Impact of acquired broad-spectrum β-lactamases on susceptibility to oral penems/carbapenems (tebipenem, sulopenem, and faropenem) alone or in combination with avibactam and taniborbactam β-lactamase inhibitors in Escherichia coli.
The impact of β-lactamases on susceptibility to oral penems/carbapenems (tebipenem, sulopenem, and faropenem) and other carbapenem molecules was evaluated in Escherichia coli, alone and in combination with avibactam or taniborbactam β-lactamase inhibitors. Tebipenem and sulopenem exhibited a similar spectrum of activity compared to the intravenous carbapenems and displayed lower MIC values than ceftibuten-avibactam against E. coli producing extended-spectrum β-lactamases or AmpC enzymes. Combined with taniborbactam, tebipenem and sulopenem exhibited low MIC values against almost all tested recombinant E. coli, including metallo-β-lactamase producers.


Effects of cyclosporin A on the immune responses and pathogenesis of a virulent strain of Mycoplasma gallisepticum in chickens.
Immune responses to the virulent S6 strain of Mycoplasma gallisepticum in immunocompetent and cyclosporin A (CsA)-treated specific pathogen free chickens were investigated, and pathogenesis of the M. gallisepticum strain was also examined. Ten-day-old specific pathogen free chickens were inoculated by eye-drop with M. gallisepticum, and a control uninfected group was inoculated with mycoplasma broth. Blood was collected weekly for 4 weeks from five birds in each group and whole blood lymphocyte transformation assayed against concanavalin A and lipopolysaccharide. Blood samples were also collected at intervals for serological assays. Live body weight, clinical signs and lesions were monitored, and recovery of M. gallisepticum was attempted from choanal cleft of live birds and also from various sites at necropsy. In parallel to the aforementioned groups, another set of two groups of chicks treated with CsA was infected with M. gallisepticum S6 or mycoplasma broth. These groups were subjected to the same experimental procedures. In the immunocompetent chickens, M. gallisepticum caused temporary T-cell suppression at 2 weeks post-infection. Comparison of the clinical signs and macroscopic lesions produced in immunocompetent and CsA-treated chickens indicated that T cells may not play an active role in disease development. The percentage of birds with mycoplasma isolation and the load of mycoplasmas suggested that T cells may have some role in resisting mycoplasma colonization or in the elimination of the infection.


Dysregulation of the behavioral activation system in remitted bipolar I disorder.
The current study tests a prediction of the behavioral activation system (BAS) dysregulation theory of bipolar disorder, namely that following high levels of reward or frustration, individuals with bipolar disorder will take longer than will healthy controls to recover to baseline levels of BAS activity. Eighty individuals (40 with bipolar I disorder, currently euthymic; 40 with no history of affective disorder) completed a daily diary over a 28 day period. No differences were found between the 2 groups in terms of the relation among levels of reward or frustration experienced, magnitude of initial response, or time taken to recover. However, examination of the relation between number of previous episodes and time to recover revealed that history of mania was associated with prolonged activation following reward, whereas history of both mania and depression were associated with prolonged recovery following frustration. The findings do not support an association between lifetime diagnosis of bipolar disorder and slow recovery of BAS activity. Nevertheless, they offer tentative support for an association between number of previous episodes and slow recovery of BAS activity.


How strong is the evidence that Parkinson's disease is a prion disorder?
We describe evidence supporting the hypothesis that α-synuclein has a prion-like role in Parkinson's disease and related α-synucleinopathies, and discuss how this novel thinking impacts the development of diagnostics and disease-modifying therapies. Observations that immature dopamine neurons grafted to Parkinson's disease patients can develop Lewy bodies triggered a surge of interest in the putative prion-like properties of α-synuclein. We recount results from experiments which confirm that misfolded α-synuclein can exhibit disease-propagating properties, and describe how they relate to the spreading of α-synuclein aggregates in α-synucleinopathies. We share insights into the underlying molecular mechanisms and their relevance to novel therapeutic targets. Finally, we discuss what the initial triggers of α-synuclein misfolding might be, where in the body the misfolding events might take place, and how this can instruct development of novel diagnostic tools. We speculate that differences in anatomical trigger sites and variability in α-synuclein fibril structure can contribute to clinical differences between α-synucleinopathies. The realization that α-synuclein pathology can propagate between brain regions in neurodegenerative diseases has deepened and expanded our understanding of potential pathogenic processes which can lead to the development of novel diagnostic tools as well as the identification of new therapeutic targets.


Closed-economy energetics.
When the behavioral cost of access to food is increased in the 24 h closed-economy procedure, the number of meals per day decreases, the amount consumed per meal increases, and the total daily food intake remains relatively constant. This "Collier function" is found widely in individuals of different species and poses interesting questions about the mechanisms by which behavioral cost achieves these effects on feeding. Data from experiments with pigeons are reviewed which show that: (a) behavioral costs that differentially alter ingestive behavior are not differentiated by energetic costs (VO(2)), (b) the effects of a rise in behavioral cost of food require several days for full expression in ingestive behavior, (c) a bimodal distribution of feeding activity across the active phase is conserved when increased costs reduce the number of meals per day, (d) when ingestive behavior fails to supply a satisfactory nutrient load, physiological and behavioral energy-saving responses occur during the inactive phase. Mechanisms responsible for behavioral-cost effects on feeding will need to make provision for development of the effects across days, conservation of within-day distribution of feeding activity, and apparent lack of differential feed back from energy expenditure related to the differential behavioral costs. A complete energetic picture of life in a closed economy will include the inactive phase of the day and consideration of the effects of ambient temperature.


Recent advances in personalizing cardiac arrest resuscitation.
Cardiac arrest remains a significant cause of death and disability throughout the world. However, as our understanding of cardiac arrest and resuscitation physiology has developed, new technologies are fundamentally altering our potential to improve survival and neurologic sequela. Some advances are relatively simple, requiring only alterations in current basic life support measures or integration with pre-hospital organization, whereas others, such as extra-corporeal membrane oxygenation, require significant time and resource investments. When combined with consistent rescuer and patient-physiologic monitoring, these innovations allow an unprecedented capacity to personalize cardiac arrest resuscitation to patient-specific pathophysiology. However, as more extensive options are established, it can be difficult for providers to incorporate novel resuscitation techniques into a cardiac arrest protocol which can fit a wide variety of cases with varying complexity. This article will explore recent advances in our understanding of cardiac arrest physiology and resuscitation sciences, with particular focus on the metabolic phase after significant ischemia has been induced. To this end, we establish a practical consideration for providers seeking to integrate novel advances in cardiac arrest resuscitation into daily practice.


Evaluation of Combination Drug Therapy for Treatment of Antibiotic-Resistant Inhalation Anthrax in a Murine Model.
Bacillus anthracis is considered a likely agent to be used as a bioweapon, and the use of a strain resistant to the first-line antimicrobial treatments is a concern. We determined treatment efficacies against a ciprofloxacin-resistant strain of B. anthracis (Cipr Ames) in a murine inhalational anthrax model. Ten groups of 46 BALB/c mice were exposed by inhalation to 7 to 35 times the 50% lethal dose (LD50) of B. anthracis Cipr Ames spores. Commencing at 36 h postexposure, groups were administered intraperitoneal doses of sterile water for injections (SWI) and ciprofloxacin alone (control groups), or ciprofloxacin combined with two antimicrobials, including meropenem-linezolid, meropenem-clindamycin, meropenem-rifampin, meropenem-doxycycline, penicillin-linezolid, penicillin-doxycycline, rifampin-linezolid, and rifampin-clindamycin, at appropriate dosing intervals (6 or 12 h) for the respective antibiotics. Ten mice per group were treated for 14 days and observed until day 28. The remaining animals were euthanized every 6 to 12 h, and blood, lungs, and spleens were collected for lethal factor (LF) and/or bacterial load determinations. All combination groups showed significant survival over the SWI and ciprofloxacin controls: meropenem-linezolid (P = 0.004), meropenem-clindamycin (P = 0.005), meropenem-rifampin (P = 0.012), meropenem-doxycycline (P = 0.032), penicillin-doxycycline (P = 0.012), penicillin-linezolid (P = 0.026), rifampin-linezolid (P = 0.001), and rifampin-clindamycin (P = 0.032). In controls, blood, lung, and spleen bacterial counts increased to terminal endpoints. In combination treatment groups, blood and spleen bacterial counts showed low/no colonies after 24-h treatments. The LF fell below the detection limits for all combination groups yet remained elevated in control groups. Combinations with linezolid had the greatest inhibitory effect on mean LF levels.


Specificity of membrane complement receptor type three (CR3) for beta-glucans.
The binding of the iC3b receptor (CR3) to unopsonized zymosan was shown to result from CR3 attachment to cell wall beta-glucans. A specificity of neutrophil responses for beta-glucan was first suggested by a comparison of yeast (Saccharomyces cerevisiae) cell wall components for stimulation of a neutrophil superoxide burst. Neutrophils responded poorly to heat-killed yeast, but gave increasingly better responses to cell wall polysaccharides devoid of proteins (zymosan) and nearly pure beta-glucan particles derived from zymosan. Zymosan triggered a burst that was 29% as great as that stimulated by phorbol myristate acetate (PMA), and beta-glucan particles stimulated a burst that was 72% as great as that produced by PMA. Phagocytic responses to yeast were also inhibited by soluble glucans but not by soluble mannans. Three types of experiments demonstrated a role for CR3 in these responses. First, neutrophil ingestion of either yeast or yeast-derived beta-glucan particles was blocked by monoclonal anti-CR3, fluid-phase iC3b, or soluble beta-glucan from barley. Monocyte ingestion of beta-glucan particles was also blocked by anti-CR3, but not by anti-CR1 or anti-C3. Second, the neutrophil superoxide burst response to either zymosan or beta-glucan particles was blocked by anti-CR3 or fluid-phase iC3b, and was completely absent with neutrophils from 3 patients with an inherited deficiency of CR3. Third, CR3 was isolated from solubilized neutrophils by affinity chromatography on beta-glucan-Sepharose.


Early and late survival after coronary-artery surgery.
Between 1970 and 1985, 1801 patients underwent coronary-artery surgery without associated valvular surgery. Eighty-four per cent of patients were male and the mean (+/- SD) age was 55.7 +/- 8.3 years. Of the patients, 18.7% were from the Coronary Care Unit and 6.5% had diabetes. The hospital mortality rate for the whole group was 3.5%. Patients from the Coronary Care Unit had the highest (8.9%) hospital mortality rate compared with those patients who were not from the Coronary Care Unit (2.1%; P less than 0.001). Other factors which increased the hospital mortality rate significantly were the number of diseased vessels (P less than 0.01), the degree of left main coronary-artery stenosis (P less than 0.001), an earlier year of surgery (P less than 0.01) and female sex (P less than 0.01). After these were taken into account, no other factors (for example, age, preoperative infarction, presence of left-ventricular aneurysm, left-ventricular end-diastolic pressure, diabetes, use of mammary-arterial grafts or the need for endarterectomy) affected the mortality rate. Patients were followed-up for a mean (+/- SD) of 4.4 +/- 2.8 years. The five-year survival rate for all patients was 88% and the 10-year survival rate was 65%. Cox regression analysis showed that the significant indicators of decreased long-term survival were undergoing operation directly from the Coronary Care Unit (P less than 0.001), left main coronary-artery stenosis (P less than 0.01), the number of grafted vessels (P less than 0.01), concomitant surgery for aneurysm (P less than 0.001), year of surgery (P less than 0.01). Seventy-nine per cent of patients were free of angina pectoris at five years after operation. The year of surgery (P less than 0.001) and preoperative myocardial infarction (P less than 0.05) were the best predictors of recurrent angina. In the long term, recurrent angina remains a problem, although this may change with the increased use of mammary-arterial grafts.


Perchlorates on Mars enhance the bacteriocidal effects of UV light.
Perchlorates have been identified on the surface of Mars. This has prompted speculation of what their influence would be on habitability. We show that when irradiated with a simulated Martian UV flux, perchlorates become bacteriocidal. At concentrations associated with Martian surface regolith, vegetative cells of Bacillus subtilis in Martian analogue environments lost viability within minutes. Two other components of the Martian surface, iron oxides and hydrogen peroxide, act in synergy with irradiated perchlorates to cause a 10.8-fold increase in cell death when compared to cells exposed to UV radiation after 60 seconds of exposure. These data show that the combined effects of at least three components of the Martian surface, activated by surface photochemistry, render the present-day surface more uninhabitable than previously thought, and demonstrate the low probability of survival of biological contaminants released from robotic and human exploration missions.


Population genetic structure and connectivity of a riparian selfing herb Caulokaempferia coenobialis at a fine-scale geographic level in subtropical monsoon forest.
Rivers and streams facilitate movement of individuals and their genes across the landscape and are generally recognized as dispersal corridors for riparian plants. Nevertheless, some authors have reported directly contrasting results, which may be attributed to a complex mixture of factors, such as the mating system and dispersal mechanisms of propagules (seed and pollen), that make it difficult to predict the genetic diversity and population structure of riparian species. Here, we investigated a riparian self-fertilizing herb Caulokaempferia coenobialis, which does not use anemochory or zoochory for seed dispersal; such studies could contribute to an improved understanding of the effect of rivers or streams on population genetic diversity and structure in riparian plants. Using polymorphic ISSR and cpDNA loci, we studied the effect at a microgeographic scale of different stream systems (a linear stream, a dendritic stream, and complex transverse hydrological system) in subtropical monsoon forest on the genetic structure and connectivity of C. coenobialis populations across Dinghu Mountain (DH) and Nankun Mountain (NK). The results indicate that the most recent haplotypes (DH: H7, H8; NK: h6, h7, h11, h12) are not shared among local populations of C. coenobialis within each stream system. Furthermore, downstream local populations do not accumulate genetic diversity, whether in the linear streamside local populations across DH (H: 0.091 vs 0.136) or the dendritic streamside local populations across NK (H: 0.079 vs 0.112, 0.110). Our results show that the connectivity of local C. coenobialis populations across DH and NK can be attributed to historical gene flows, resulting in a lack of spatial genetic structure, despite self-fertilization. Selfing C. coenobialis can maintain high genetic diversity (H = 0.251; I = 0.382) through genetic differentiation (GST = 0.5915; FST = 0.663), which is intensified by local adaptation and neutral mutation and/or genetic drift in local populations at a microgeographic scale. We suggest that streams are not acting as corridors for dispersal of C. coenobialis, and conservation strategies for maintaining genetic diversity of selfing species should be focused on the protection of all habitat types, especially isolated fragments in ecosystem processes.


No Difference in Functional, Radiographic, and Survivorship Outcomes Between Direct Anterior or Posterior Approach THA: 5-Year Results of a Randomized Trial.
Both the direct anterior approach (DAA) and posterior approach (PA) to THA have known advantages and disadvantages. The comparison between DAA and PA THA has been widely explored during the early postoperative period. However, few randomized trials have compared these approaches at a minimum follow-up of 5 years; doing so would be important to establish any differences in mid-term outcomes or complications. We performed a randomized trial comparing DAA and PA in THA in terms of (1) patient-reported outcome scores, (2) quality of life and functional outcomes assessed by the EQ-5D and 10-meter walk test results, (3) radiographic analysis, and (4) survivorship and surgical complications at a minimum of 5 years follow-up. Two hip specialist surgeons performed both DAA and PA THA using the same THA components at two hospital sites. One hundred twelve patients on the elective THA surgical waitlist were invited to participate in the study. Thirty-four patients did not meet the study's inclusion criteria and were excluded, and three patients declined to participate in the study. The remaining 75 patients who were eligible were randomized into DAA and PA groups. Thirty-seven patients were initially randomized to receive DAA THA, but two did not and were excluded, resulting in 48% (35 of 73) of patients who received DAA THA; 52% (38 of 73) of patients were randomized into and received PA THA. Over a minimum 5 years of follow-up, 3% (1 of 35) of DAA patients were lost to follow-up, and none of the patients undergoing PA THA were lost. A per-protocol analysis was adopted, resulting in further patients being excluded from analysis. Of the 73 study patients, 99% (72; DAA: 35, PA: 37) were analyzed at 1 year, 95% (69; DAA: 34, PA: 35) were analyzed at 2 years, and 72% (52; DAA: 23, PA: 29) were analyzed at 5 years. The primary outcome was the Oxford Hip Score (OHS) and WOMAC score. Secondary outcomes included the EQ-5D and EQ-5D VAS scores, 10-meter walk test results, radiographic evidence of loosening (femoral: lucency > 2 mm at the implant-bone interface, subsidence > 2 mm; acetabular: migration or change in inclination), 5-year survivorship analysis from all-cause revisions, and surgical complications. The study was powered to detect a 10-point difference in the WOMAC score, which is equivalent to the minimum clinically important difference (MCID). There were no differences in primary outcomes (OHS and WOMAC scores) or secondary outcomes (EQ-5D scores, EQ-5D VAS scores, and 10-meter walk test result) between the DAA and PA groups at the 5-year follow-up interval. The median (range) OHS at 5 years was 46 (16 to 48) for DAA and 47 (18 to 48) for PA groups (p = 0.93), and the median WOMAC score was 6 (0 to 81) for DAA and 7 (0 to 59) for PA groups (p = 0.96). The median EQ-5D score was 1 (0.1 to 1) for DAA and 1 (0.5 to 1) for PA groups (p = 0.45), and the median EQ-5D VAS score was 85 (60 to 100) for DAA and 95 (70 to 100) for PA groups (p = 0.29). There were no cases of component loosening on radiographs. There was no difference in component survival between the two approaches at 5 years (DAA: 97% [95% CI 85% to 100%] versus PA: 97% [95% CI 87% to 100%]). Eight of 23 patients in the DAA group reported decreased sensation in the lateral femoral cutaneous nerve distribution. DAA and PA are both effective approaches in performing primary THA. Each approach has its associated risks and complications. The choice of THA should be based on individual patient factors, surgeon experience, and shared decision-making. Early registry data indicate DAA and PA THA are comparable, but longer-term data with larger numbers of patients will be required before one can safely conclude equal survivorship between both approaches. Level I, therapeutic study.


Vegetables and Mixed Dishes Are Top Contributors to Phylloquinone Intake in US Adults: Data from the 2011-2012 NHANES.
Background: Phylloquinone is the most abundant form of vitamin K in US diets. Green vegetables are considered the predominant dietary source of phylloquinone. As our food supply diversifies and expands, the food groups that contribute to phylloquinone intake are also changing, which may change absolute intakes. Thus, it is important to identify the contributors to dietary vitamin K estimates to guide recommendations on intakes and food sources.Objective: The purpose of this study was to estimate 1) the amount of phylloquinone consumed in the diet of US adults, 2) to estimate the contribution of different food groups to phylloquinone intake in individuals with a high or low vegetable intake (≥2 or <2 cups vegetables/d), and 3) to characterize the contribution of different mixed dishes to phylloquinone intake.Methods: Usual phylloquinone intake was determined from NHANES 2011-2012 (≥20 y old; 2092 men and 2214 women) and the National Cancer Institute Method by utilizing a complex, stratified, multistage probability-cluster sampling design.Results: On average, 43.0% of men and 62.5% of women met the adequate intake (120 and 90 μg/d, respectively) for phylloquinone, with the lowest self-reported intakes noted among men, especially in the older age groups (51-70 and ≥71 y). Vegetables were the highest contributor to phylloquinone intake, contributing 60.0% in the high-vegetable-intake group and 36.1% in the low-vegetable-intake group. Mixed dishes were the second-highest contributor to phylloquinone intake, contributing 16.0% in the high-vegetable-intake group and 28.0% in the low-vegetable-intake group.Conclusion: Self-reported phylloquinone intakes from updated food composition data applied to NHANES 2011-2012 reveal that fewer men than women are meeting the current adequate intake. Application of current food composition data confirms that vegetables continue to be the primary dietary source of phylloquinone in the US diet. However, mixed dishes and convenience foods have emerged as previously unrecognized but important contributors to phylloquinone intake in the United States, which challenges the assumption that phylloquinone intake is a marker of a healthy diet. These findings emphasize the need for the expansion of food composition databases that consider how mixed dishes are compiled and defined.


Effect of graphene oxide on the properties of its composite with polyaniline.
Graphene oxide, a single layer of graphite oxide (GO), has been used to prepare graphene oxide/polyaniline (PANI) composite with improved electrochemical performance as supercapacitor electrode by in situ polymerization using a mild oxidant. The composites are synthesized under different mass ratios, using graphite as start material with two sizes: 12 500 and 500 mesh. The result shows that the morphology of the prepared composites is influenced dramatically by the different mass ratios. The composites are proposed to be combined through electrostatic interaction (doping process), hydrogen bonding, and pi-pi stacking interaction. The highest initial specific capacitances of 746 F g(-1) (12 500 mesh) and 627 F g(-1) (500 mesh) corresponding to the mass ratios 1:200 and 1:50 (graphene oxide/aniline) are obtained, compared to PANI of 216 F g(-1) at 200 mA g(-1) by charge-discharge analysis between 0.0 and 0.4 V. The improved capacitance retention of 73% (12 500 mesh) and 64% (500 mesh) after 500 cycles is obtained for the mass ratios 1:23 and 1:19 compared to PANI of 20%. The enhanced specific capacitance and cycling life implies a synergistic effect between two components. This study is of significance for developing new doped PANI materials for supercapacitors.


On the differences in degree of renewal produced by the different renewal designs.
This paper addresses sources contributing to the differences in the degree of recovery from extinction observed with different renewal paradigms. In two lick suppression experiments with rats, we assessed the role of the associative status of the acquisition context in both the weakness of AAC renewal and the sometimes observed weaker renewal resulting from an ABC design relative to an ABA design. In Experiment 1, we observed that AAC renewal relative to an AAA control group was small unless Context A had undergone associative deflation (i.e., extinction of Context A). Deflation of Context A not only decreased behavioral control by the CS in the AAA condition, but increased it in the AAC condition, thereby implicating a comparator process in addition to associative summation between the CS and test context. In Experiment 2, an excitatory acquisition context was found to enhance the difference between ABC and ABA renewal. Associative deflation of the acquisition context decreased ABA renewal more than ABC renewal. Thus, the associative value of the acquisition context (A) was more positively related to the level of renewal when the target CS (X) was tested in this context than when it was tested in a neutral but equally familiar context (C), consistent with the frequently observed greater renewal in an ABA condition than an ABC condition arising from associative summation of the CS and test context. These findings demonstrate that the excitatory status of the acquisition context influences the observed degree of renewal.


Effect of "missing" information on fast mapping by individuals with vocabulary limitations associated with intellectual disability.
One phenomenon of language development is a dramatic increase in vocabulary size, driven by rapid word learning. For individuals with intellectual disabilities, the size of the lexicon often lags behind what would be expected both for CA and MA. I examined how well individuals with severely limited receptive vocabulary associated with intellectual disability retained a new word-picture map after a single exposure under conditions of varying difficulty. This study was a direct replication of a previous investigation with typically developing preschool children, enabling a direct comparison. Individuals with intellectual disabilities performed equally as well as control children in the initial exposure phase but poorer when asked to remember the initial map in the presence of other novel distracters or labels.


Susceptibility genes for nontuberculous mycobacterial disease.
The number of patients with nontuberculous mycobacterial (NTM) disease is reportedly increasing both in Japan and worldwide. NTM diseases are classified into disseminated and pulmonary diseases based on their clinical characteristics. These two types of NTM diseases are thought to be controlled by different mechanisms. Disseminated NTM disease is caused by a defect in signal transduction of Th1 cellular immune responses, including the IFN-γ/IL-12 axis. The precise molecular mechanisms of disseminated NTM disease are understood in detail. Pulmonary NTM disease progression is associated with both bacterial factors as well as host factors. Furthermore, it is suggested that some susceptibility genes for NTM diseases may also exist. A previous study on the susceptibility genes for pulmonary NTM disease was performed using Single Nucleotide Polymorphism (SNP) analysis and microsatellite marker analysis. However, a number of challenges remain in terms of the reproducibility. The emergence of next generation sequencing enables genome-wide analysis, and further studies on the susceptibility genes for pulmonary NTM disease are expected in the future.


[In vitro effect of an alkaloid isolated from Amphimedon viridis (Porifea) on promastigots of Leishmania mexicana].
The dose dependent antiproliferative effect of an alkaloidal substance extracted from the sponge Amphimedon viridis was tested on Leishmania mexicana promastigotes. Sponges were collected in Isla Larga, Venezuela (10 degrees 20' 20" - 10 degrees 24" N, 64 degrees 19' - 64 degrees 22' W), cut and dipped in methanol for vacum filtering extraction every 24 hr. The aqueous extract was separated by chromatography over silica gel. The parasites were from the Venezuelan NR strain. Their growth rate was reduced by 50 % with a dose of 10 microg/ml in 48 hr, whilst concentrations of 30 and 40 microg/ml induce leishmanicidal action after 110 and 20 min, respectively. Lysis is preceded by an immediate increase in cellular volume associated with progressive damage of cellular content and the destruction of organelles. These findings suggest that one important factor associated with the antiproliferative effect of this alkaloidal substance on L. mexicana promastigotes is the loss of the plasma membrane selective permeability.


Genetic variability of E. histolytica strains based on the polymorphism of the SREHP gene using nested PCR-RFLP in Erbil, North Iraq.
E. histolytica is an intestinal parasite that causes asymptomatic infection mostly; however, it may also cause amoebic dysentery and liver abscess. Molecular identification is required in epidemiological studies due to the presence of morphologically identical nonpathogenic species. Therefore, this study was conducted to first evaluate the prevalence rate of E. histolytica among symptomatic individuals of Erbil city, and to investigate the genetic diversity of the parasite in a limited geographic area. Accordingly, a total of 2026 samples were examined microscopically, and confirmed by nested PCR for 18s rRNA gene. The results showed that the prevalence rate of E. histolytica was 1.97% (40 samples) among symptomatic patients. The SREHP gene was used as a marker to show the genetic polymorphism of E. histolytica; however, to compare the genetic diversity of symptomatic with asymptomatic isolates, 57 asymptomatic samples were obtained from our previous study. The amplified products of the SREHP gene were digested by AluI endonuclease, and DNA banding patterns were analysed. Results showed 29 different DNA patterns among the 97 symptomatic and asymptomatic samples, 62 of which shared similar DNA patterns. However, 8 different DNA patterns were observed among asymptomatic samples, whereas 15 distinct patterns were observed among symptomatic isolates. In conclusion, this study found that the prevalence rate of E. histolytica was relatively low; relatively high genetic diversity was observed in a restricted endemic area; with higher rates of variability in symptomatic rather than in asymptomatic isolates, indicating a possible correlation between the genotype of E. histolytica and their clinical outcome.


Dermatophytic pseudomycetomas in two ferrets (Mustela putorius furo).
Dermatophytic pseudomycetoma is an atypical form of dermatophytosis where the infection is located in the deep dermal and subcutaneous tissues. Although rare, it is most commonly associated with Microsporum canis or Trichophyton sp. It has been reported in cats, dogs and horses. To describe the clinical and pathological findings of dermatophytic pseudomycetoma caused by M. canis and Trichophyton sp. in two domestic ferrets. Two pet ferrets (Mustela putorius furo). Case report. Two ferrets were diagnosed with dermatophytic pseudomycetoma confirmed by histological examination of tissue and fungal culture. In both cases, ferrets presented with several cutaneous firm nodules 0.6-3 cm in diameter. Microscopic lesions revealed multifocal nodular pyogranulomatous inflammation with intralesional fungi. To the best of the authors' knowledge, this is the first description of dermatophytic pseudomycetoma in domestic ferrets. This disease should be included in the differential diagnosis of nodular dermatopathies in this species.


Rapid increase of Plasmodium falciparum dhfr/dhps resistant haplotypes, after the adoption of sulphadoxine-pyrimethamine as first line treatment in 2002, in southern Mozambique.
In late 2002, the health authorities of Mozambique implemented sulphadoxine-pyrimethamine (SP)/amodiaquine (AQ) as first-line treatment against uncomplicated falciparum malaria. In 2004, this has been altered to SP/artesunate in line with WHO recommendations of using Artemisinin Combination Therapies (ACTs), despite the fact that all the neighbouring countries have abandoned SP-drug combinations due to high levels of SP drug resistance. In the study area, one year prior to the change to SP/AQ, SP alone was used to treat uncomplicated malaria cases. The study described here investigated the immediate impact of the change to SP on the frequency of SP and CQ resistance-related haplotypes in the Plasmodium falciparum genes Pfdhfr, Pfdhps and Pfcrt before and a year after the introduction of SP. Samples were collected during two cross sectional surveys in early 2002 and 2003 involving 796 and 692 children one year or older and adults randomly selected living in Maciana, an area located in Manhiça district, Southern Mozambique. Out of these, 171 and 173 P. falciparum positive samples were randomly selected to measure the frequency of resistance- related haplotypes in Pfdhfr, Pfdhps and Pfcrt based on results obtained by nested PCR followed by sequence-specific oligonucleotide probe (SSOP)-ELISA. The frequency of the SP-resistance associated Pfdhps double mutant (SGEAA) haplotype increased significantly from 14% to 35% (P < 0.001), while the triple mutant Pfdhfr haplotype (CIRNI) remained high and only changed marginally from 46% to 53% (P = 0.405) after one year with SP as first-line treatment in the study area. Conversely, the combined Pfdhfr/Pfdhps quintuple mutant haplotype increased from 8% to 26% (P = 0.005). The frequency of the chloroquine resistance associated Pfcrt-CVIET haplotype was above 90% in both years. These retrospective findings add to the general concern on the lifespan of the combination of SP/artesunate in Mozambique. The high frequency of quintuple Pfdhfr/Pfdhps haplotypes found here as early as 2002 most likely cause ideal conditions for the development of artesunate tolerance in the P. falciparum populations and may even endanger the sensitivity to the second-line drug, Coartem.


Fluorinated Sulfilimino Iminiums: Efficient and Versatile Sources of Perfluoroalkyl Radicals under Photoredox Catalysis.
Reported herein is the use of S-perfluoroalkyl sulfilimino iminiums as a new source of RF radicals under visible-light photoredox catalysis (RF =CF3 , C4 F9 , CF2 Br, CFCl2 ). These shelf-stable perfluoroalkyl reagents, readily prepared on gram scale from the corresponding sulfoxide using a one-pot procedure, allow the efficient photoredox-induced oxyperfluoroalkylation of various alkenes using fac-Ir(ppy)3 as the photocatalyst. Importantly, spin-trapping/electron paramagnetic resonance experiments were carried out to characterize all the radical intermediates involved in this radical/cationic process.


Sugar Beverages and Dietary Sodas Impact on Brain Health: A Mini Literature Review.
Sugar-sweetened beverages containing caffeine are widely used among humans nowadays and can have negative consequences on the overall health. Our study aims to discuss the effects of these sugar-sweetened beverages (SSB) and how they can impact the health in different ways particularly on the brain. Some of the mechanisms by which soft drinks can exert adverse effects include an increase in glutathione-6-dehydrogenase level, increased levels of gamma-aminobutyric acid (GABA), glutamate and dopamine alteration in brain waves on electroencephalography (EEG) eventually leading to stroke and dementia. They can increase the oxidative stress by a decreasing monoamine oxidase and acetylcholine esterase and antioxidants such as glutathione and catalase. The sleep quality and duration of sleep is also significantly affected by their increased consumption. Also, the consumption of sodium benzoate (found in beverages) on impairing memory, motor coordination, affecting reduced glutathione (GSH), increasing the malondialdehyde (MDA) level in the brain and producing attention deficit hyperactivity disorder (ADHD) in children is emphasized. Finally, we will highlight how diet drinks can also be harmful and the maternal consumption of chocolate or soft drinks during pregnancy and postnatal period can be linked to cognitive impairment and child obesity.


Comparative studies of lymph node cell subpopulations and cytokine expression in murine model for testing the potentials of chemicals to induce respiratory sensitization.
To investigate immunological changes in lymph nodes based on expression of cell-specific receptors and cytokine expression profile and accompanying inflammatory reactions in lungs of mice treated with chemicals of known potentials to induce respiratory sensitization and those in which activity in this regard is unclear. On day 1 and 7, Balb/c mice received toluene-2,4-diisocyanate (TDI), trimellitic anhydride (TMA), 1-chloro-2,4-dinitrobenzene (DNCB), glutaraldehyde (GA), formaldehyde (FA), benzalkonium chloride (ChB) or vehicle. On day 14, they received a single intranasal instillation with the same chemical or vehicle. On day 15, auricular lymph nodes (LN) were excised and used for analyzes of T-, B-cells, expression of CD44 and for the estimation of IL-4 and IFN-gamma production after in vitro stimulation with concanavalin A (ConA) and also for IL-4 and IFN-gamma mRNA expression analyses using Real-Time PCR. Inflammatory changes in lungs were observed by estimation of TNF-alpha and MIP-2 concentrations and cell numbers and their type in BAL. There were no significant changes in cell subpopulations of T helper cells in LN. The percent of B cells was significantly increased after treatment with DNCB, TDI, and GA. Increased expression of CD44 on T cells was also observed. Both IL-4 and IFN-gamma were found increased in TDI- and FA-treated mice, while only IL-4 was increased in TMA-treated mice. Real-Time PCR analyses, however, showed increased IL-4 mRNA expression for TDI- and TMA-, and IFN-gamma mRNA expression for DNCB-treated mice. We haven't observed significant changes in inflammatory reactions in the lungs of exposed animals. Studying immunological changes with first determining the activation status of T cells followed by analyzes of expression of mRNA for Th1 and Th2 cytokines in murine model could be a useful method for assessment of the potentials of chemicals to induce respiratory sensitization but is not sufficient. Addition of ventilatory measurements, but not necessarily inflammatory reactions, could complete the model.


Differentials in prevalence and correlates of metabolic risk factors of non-communicable diseases among women in sub-Saharan Africa: evidence from 33 countries.
Even with the widespread recognition of non- communicable diseases (NCDs) in sub-Saharan Africa region, yet, sufficient evidence-based surveillance systems to confirm the prevalence and correlates of these diseases is lacking. In an attempt to understand the problem of NCDs in resource-constrained settings, this study was conducted to establish the pattern of the risk factors of NCDs in sub-Sahara Africa region. The current Demographic and Health Survey (DHS) data sets from 33 countries in sub-Sahara Africa region were used in this study. The individual woman component of DHS 2008-2016 was used. The outcome variables include anemia, hypertension and body mass index (underweight, overweight and obesity). BMI was categorized into; underweight (BMI < 18.5 kg/m2), normal (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obesity (BMI ≥30 kg/m2). Hemoglobin level: anemic < 12.0 g/dL (< 120 g/L) for women. Hypertension was defined as systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg. Binary and multinomial logistic regression models were used to investigate the correlates of the variables. The percentage of hypertension was highest among women in Lesotho with about 17.3% and lowest among women in Burundi (1.0%). Anemia was prevalent among sub-Saharan Africa women; where more than half of the women from several countries were anemic with Gabon (60.6%) reporting the highest prevalence. The percentage of obesity in sub-Saharan Africa showed that Lesotho (19.9%), Gabon (18.9%) and Ghana (15.6%) were the prominent countries with obese women, while Madagascar (1.1%) had the minimum obese women. Body mass index was significantly associated with hypertension and anemia. The behavioural or modifiable factors of hypertension and body mass index were; smoking, fruits, vegetables and alcohol consumption. While the non-modifiable significant factors include; age, residence, religion, education, wealth index, marital status, employment and number of children ever born. However, anemia shared similar factors except that smoking and vegetable consumption were not statistically significant. In addition, involvement in exercise was associated with anemia and hypertension. The problem of NCDs and associated factors remains high among women of reproductive age in sub-Sahara region. The findings of this study suggest that promotion of regular positive health care-seeking behaviour, screening and early treatment are essential to mitigate the burden of NCDs. Furthermore, preventive interventions of NCDs risk factors should be strengthened among key population through behavior change communication with support from government and stakeholders in health care.


Chronic thromboembolic pulmonary hypertension--diagnosed on spiral CT angiography.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a part of the spectrum of venous thromboembolism in which pulmonary thrombus fails to resolve, resulting in occlusion of the major pulmonary artery. Diagnosis of this disease is important as it is potentially curable by pulmonary thromboendarterectomy. A case of CTEPH diagnosed non-invasively on spiral computerized (CT) pulmonary angiography is reported.


Gene Therapy, A Potential Therapeutic Tool for Neurological and Neuropsychiatric Disorders: Applications, Challenges and Future Perspective.
Neurological and neuropsychiatric disorders are the main risks for the health care system, exhibiting a huge socioeconomic load. The available range of pharmacotherapeutics mostly provides palliative consequences and fails to treat such conditions. The molecular etiology of various neurological and neuropsychiatric disorders is mostly associated with a change in genetic background, which can be inherited/triggered by other environmental factors. To address such conditions, gene therapy is considered a potential approach claiming a permanent cure of the disease primarily by deletion, silencing, or edition of faulty genes and by insertion of healthier genes. In gene therapy, vectors (viral/nonvial) play an important role in delivering the desired gene to a specific region of the brain. Targeted gene therapy has unraveled opportunities for the treatment of many neurological and neuropsychiatric disorders. For improved gene delivery, the current techniques mainly focus on designing a precise viral vector, plasmid transfection, nanotechnology, microRNA, and in vivo clustered regulatory interspaced short palindromic repeats (CRISPR)-based therapy. These latest techniques have great benefits in treating predominant neurological and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder, as well as rarer diseases. Nevertheless, all these delivery methods have their limitations, including immunogenic reactions, off-target effects, and a deficiency of effective biomarkers to appreciate the effectiveness of therapy. In this review, we present a summary of the current methods in targeted gene delivery, followed by the limitations and future direction of gene therapy for the cure of neurological and neuropsychiatric disorders.


[Properties of a triphenylmethane dyes decolorization enzyme (TpmD) from Aeromonas hydrophila strain DN322].
A novel bacterial enzyme for decolorization of triphenylmethane dyes from Aeromonas hydrophila strain DN322 was purified and named TpmD. The basic properties of this enzyme including molecular weight, isoelectric point Km as well as the optimum temperature and pH were determined and the enzyme was identified as an NADH/NADPH-dependent oxygenase in previous research. Based on previous results, the effect of different inhibitor including Vc, metyrapone, rotenone, antimycin A and NaN3 as well as the effect of FAD and FMN on the activity of TpmD were measured. The results indicated that the activity of the decolorization enzyme was inhibited by Vc and metyrapone in a concentration-dependent manner, but wasn't inhibited by rotenone, antimycin A and NaN3. The activity of the decolorization enzyme was not enhanced by addition of FAD or FMN. The solution of the enzyme protein displayed only a single peak at 408nm in the Soret region, a characteristic peak of porphyrin, but did not show the characteristic peak of the cytochrome P450 proteins at 450nm in sodium dithionite (DTN)-reduced enzyme solution after treatment with carbon monoxide. The amino acid sequence of N-terminal of TpmD provided further evidence that the enzyme is an oxygenase. All these results suggest that decolorization enzyme TpmD is a new hemo-containing oxygenase. The decolorization enzyme would be a good material for further research of the enzymological mechanism of triphenylmethane dyes decolorization by bacteria.


Towards in vivo estimation of reaction kinetics using high-throughput metabolomics data: a maximum likelihood approach.
High-throughput assays such as mass spectrometry have opened up the possibility for large-scale in vivo measurements of the metabolome. This data could potentially be used to estimate kinetic parameters for many metabolic reactions. However, high-throughput in vivo measurements have special properties that are not taken into account in existing methods for estimating kinetic parameters, including significant relative errors in measurements of metabolite concentrations and reaction rates, and reactions with multiple substrates and products, which are sometimes reversible. A new method is needed to estimate kinetic parameters taking into account these factors. A new method, InVEst (In Vivo Estimation), is described for estimating reaction kinetic parameters, which addresses the specific challenges of in vivo data. InVEst uses maximum likelihood estimation based on a model where all measurements have relative errors. Simulations show that InVEst produces accurate estimates for a reversible enzymatic reaction with multiple reactants and products, that estimated parameters can be used to predict the effects of genetic variants, and that InVEst is more accurate than general least squares and graphic methods on data with relative errors. InVEst uses the bootstrap method to evaluate the accuracy of its estimates. InVEst addresses several challenges of in vivo data, which are not taken into account by existing methods. When data have relative errors, InVEst produces more accurate and robust estimates. InVEst also provides useful information about estimation accuracy using bootstrapping. It has potential applications of quantifying the effects of genetic variants, inference of the target of a mutation or drug treatment and improving flux estimation.


Workshops in personal relationships.
This paper describes the planning, implementation and evaluation of a series of workshops for practising health visitors, as one aspect of continuing professional education. The history demonstrates response to stated need. Planning was intensive and extensive, resulting in one broad educational objective and a flexible approach to teaching/learning, contributions of expertise from several disciplines proved valuable. Prior to full implementation, experimental workshops were organized and evaluated both objectively and subjectively. The variety of methods of evaluation permitted isolation of some factors which mitigate against success and their avoidance when possible. The objective evaluations used three criteria which appeared to demonstrate positive outcomes to a great extent. Evaluations of 17 workshops demonstrate the continuing value of this form of education, and the summarized response shows, inter alia, that impetus does not necessarily reduce with time. Of significance is the evidence that the results include improved professional practice and that there were increases in depth and breadth of knowledge. Additionally, there were developments of self-help and professional interest groups. Finally, the sequel should lead towards a model of training resource personnel within the NHS, the trial of the model being early in 1982.


A comparison of dexmedetomidine, and alpha 2-adrenoceptor agonist, and midazolam as i.m. premedication for minor gynaecological surgery.
The effects of i.m. dexmedetomidine 1.0 micrograms kg-1, a new alpha 2-adrenoceptor agonist, were compared with those of i.m. midazolam 0.08 mg kg-1 and placebo on vigilance, anaesthetic requirements, haemodynamic state and plasma catecholamine concentrations in a double-blind placebo-controlled study in 107 healthy (ASA physical status I-II) women undergoing cervical dilatation and uterine curettage. The premedicants were administered i.m. 60 min before induction of anaesthesia with thiopentone. Nitrous oxide 70% in oxygen and thiopentone were used for maintenance. Both premedicants were tolerated well and no serious haemodynamic or other adverse events occurred. Dexmedetomidine caused moderate reductions in arterial pressure (maximally by 20%) and heart rate (maximally by 15%). Atropine was administered to two dexmedetomidine-premedicated patients because of bradycardia less than 45 beat min-1. Both premedicants decreased the plasma concentrations of noradrenaline by about 50%, but only dexmedetomidine attenuated the catecholamine response to anaesthesia and surgery. The thiopentone requirements were decreased significantly (P = 0.003) by both dexmedetomidine (17%) and midazolam (19%). Recovery times were 11.3 (SD 4.2) min after midazolam, 8.5 (5.2) min after dexmedetomidine and 5.6 (11.4) min after placebo (P = 0.006 between midazolam and placebo groups, other differences ns).


Clinical electroencephalography in a psychiatric service.
An audit of the use of clinical electroencephalography in a psychiatric service was carried out by examining the referrals for an EEG from the service over one year (11% of all referrals), comparing them with matched patient controls, rating the EEGs blindly and estimating the clinical value of the investigation for each patient; 37% were abnormal, 19% anomalous and 44% normal. The following two clusters of symptoms and signs were associated with EEG referral--the patients with "organic" mental state phenomena and/or CNS signs; EEG usually abnormal and the patients with behavioural changes that raise the suspicion of an organic process but, taken alone, are not compelling evidence of such (for example, impulsive behaviour, acute and atypical psychoses, perceptual or behavioural phenomena of the type associated with temporal lobe epilepsy in the absence of frank complex partial seizures); EEG usually normal or anomalous. Ninety-two percent of EEGs were judged to be of clinical value; 53% positive and 39% negative. Eight percent of referrals made no contribution to the clinical evaluation.


A review of the compatibility of liposome bupivacaine with other drug products and commonly used implant materials.
The compatibility of a medication with other drugs and implanted materials is an important factor impacting drug safety and efficacy. The liposomal formulation of the local anesthetic bupivacaine is designed to provide prolonged postsurgical analgesia. Its compatibility with other drugs and materials depends on the compatibility of the drug itself, along with the integrity of liposome and liposomal components. A series of studies was conducted to evaluate the compatibility of liposome bupivacaine with diluents, implanted materials, and other drugs likely to be encountered in the surgical settings in which it is used. Liposome bupivacaine demonstrated compatibility with diluents (normal saline, lactated Ringer's solution) and with implanted materials (silicone, stainless steel, titanium, polypropylene, expanded polytetrafluoro-ethylene), with little or no change in percent of free bupivacaine, packed particle volume, or particle size distribution; liposome bupivacaine exhibited little or no change in the properties of the test materials. Liposome bupivacaine had clinically meaningful interactions with other local anesthetics, including lidocaine, ropivacaine, mepivacaine, or bupivacaine HCl (at liposome bupivacaine to bupivacaine HCl ratios < 2:1), which resulted in substantial displacement and release of free bupivacaine from liposomes. Liposome bupivacaine may be locally administered after ≥ 20 minutes following local administration of lidocaine, ropivacaine, or mepivacaine. Co-administration of liposome bupivacaine and bupivacaine HCl into the same site should be at ratios ≥ 2:1. Interactions between liposome bupivacaine and epinephrine, corticosteroids, antibiotics, non-steroidal anti-inflammatory drugs, tranexamic acid, and opioid analgesics were not clinically meaningful; liposome bupivacaine may be safely co-administered with these agents. No adverse synergistic effects on liposome bupivacaine were observed in evaluations involving multiple medications compared with each drug's individual effects.


Differential localization of the Streptococcus mutans GS-5 fructan hydrolase enzyme, FruA.
Streptococcus mutans GS-5 synthesizes an exo-beta-D-fructosidase, FruA, capable of degrading levans, inulins, sucrose and raffinose, with the greatest activity on levans. A previous analysis of the deduced amino acid sequence of the FruA protein revealed the presence of a C-terminus with an LPXTGX membrane sorting sequence and membrane spanning domain, characteristic of many Gram-positive cocci surface proteins. Here it is demonstrated that FruA, which had been previously shown to exist almost exclusively as an extracellular enzyme, can be detected in significant proportions at the surface of S. mutans cells. Moreover, growth of S. mutans GS-5 at steady state in continuous culture at pH values of 7.0, 6.0, or 5.0 revealed that the amount of cell-associated enzyme increased with decreasing pH values, such that roughly 50% of the total fructanase activity of pH 5.0-grown organisms was cell-associated. This result was confirmed using anti-recombinant-FruA antisera in Western blotting of culture supernate and cell-associated enzyme preparations from chemostat-grown cells. Incubation of S. mutans at pH values of 5.0, 6.0 or 7.0 in buffered media yielded results similar to those observed in the chemostat experiments. The release of FruA from S. mutans was also shown to be inhibitable by copper, which is known to interfere with the release of the surface adhesin, P1, from intact cells and protoplasts of S. mutans. These data provide evidence for a unique post-translational mechanism for the regulation of the catabolism of polysaccharides by bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)


Evidence-based practice for pin site care in injured children.
External fixation is an accepted treatment modality for pelvic and long-bone fractures in children following a traumatic injury. One aspect of nursing care in children receiving external fixation is pin site care to prevent pin tract infection. A review of the nursing and medical literature reveals common clinical guidelines for pin site care, such as observing for infection, cleaning the sites, removing crusts, and applying dressings. There is no evidence-based practice for the care of pin sites in children or adults receiving external fixation devices for pelvic or long bone fractures to prevent infection. While the nursing literature describes pin site care techniques, the surgical literature describes the prevalence of pin tract infection. Neither set of literature consistently addresses the protocols for and outcomes in pin site care. Experimental research is needed to create evidence-based practice guidelines for pin site care to prevent pin tract infection.