X-ray requesting patterns before and after introduction of the Ottawa Knee Rules in a UK emergency department.
To compare knee radiology requesting rates among junior doctors before and after the formal introduction of the Ottawa Knee Rules (OKR) in a UK emergency department (ED), and to test the validity of the OKR for decisions on the use of radiography for acute, isolated knee injuries. All junior doctors in a district general hospital ED seeing adult patients with isolated knee injuries completed a questionnaire before and after the introduction of the OKR. All patients were followed up to obtain a final diagnosis. The outcome measures were: adherence to the OKR, the presence of a fracture and whether a radiograph had been requested. The results were analysed to determine the sensitivity, specificity, positive and negative predictive values of the OKR. Comparisons between the request rate for knee radiography before and after the introduction of the OKR were made. A total of 130 patients were enrolled and followed up over a 3-month period; 58 before and 72 after OKR introduction. The OKR had a sensitivity of 100% (71.8-100%), a specificity of 55.1% (46.1-64.1%), a positive predictive value of 18.5% (9.03-27.9%) and a negative predictive value of 100% (87.8-100%) for the detection of bony injury. The introduction of the OKR did not result in a significant reduction in the number of radiographs performed (58.6-55.6%; P= 0.726). This study shows the OKR to be a highly sensitive clinical guide with a high negative predictive value in the setting of a UK ED. It suggests that the reduction in radiograph requests seen elsewhere may not be as apparent in this setting.


A novel method incorporating gene ontology information for unsupervised clustering and feature selection.
Among the primary goals of microarray analysis is the identification of genes that could distinguish between different phenotypes (feature selection). Previous studies indicate that incorporating prior information of the genes' function could help identify physiologically relevant features. However, current methods that incorporate prior functional information do not provide a relative estimate of the effect of different genes on the biological processes of interest. Here, we present a method that integrates gene ontology (GO) information and expression data using Bayesian regression mixture models to perform unsupervised clustering of the samples and identify physiologically relevant discriminating features. As a model application, the method was applied to identify the genes that play a role in the cytotoxic responses of human hepatoblastoma cell line (HepG2) to saturated fatty acid (SFA) and tumor necrosis factor (TNF)-alpha, as compared to the non-toxic response to the unsaturated FFAs (UFA) and TNF-alpha. Incorporation of prior knowledge led to a better discrimination of the toxic phenotypes from the others. The model identified roles of lysosomal ATPases and adenylate cyclase (AC9) in the toxicity of palmitate. To validate the role of AC in palmitate-treated cells, we measured the intracellular levels of cyclic AMP (cAMP). The cAMP levels were found to be significantly reduced by palmitate treatment and not by the other FFAs, in accordance with the model selection of AC9. A framework is presented that incorporates prior ontology information, which helped to (a) perform unsupervised clustering of the phenotypes, and (b) identify the genes relevant to each cluster of phenotypes. We demonstrate the proposed framework by applying it to identify physiologically-relevant feature genes that conferred differential toxicity to saturated vs. unsaturated FFAs. The framework can be applied to other problems to efficiently integrate ontology information and expression data in order to identify feature genes.


Intravascular gas as an incidental finding at US after blunt abdominal trauma.
To describe the occurrence and importance of intravascular gas at ultrasonography (US) during the initial examination of patients after blunt abdominal trauma. Reports of all abdominal US examinations performed at one institution for blunt trauma from October 1995 through June 1996 were reviewed. The charts of patients with intravascular gas were examined to determine the mechanism of injury, associated findings, and clinical outcome. A total of 730 patients underwent abdominal US examinations during the 9 months of study; five had intravascular gas demonstrated. Two patients had portal venous gas, one had hepatic venous gas, and two had inferior vena caval gas. Four of the five patients were involved in motor vehicle accidents, and one had been assaulted. In patients in whom follow-up studies were obtained, there was no evidence of intravascular gas at US or computed tomography. No cause was found at imaging or clinical examination. Intravascular gas may occur as a transient incidental finding after blunt abdominal trauma.


Transformation of Schwanniomyces occidentalis with an ADE2 gene cloned from S. occidentalis.
We have developed an efficient transformation system for the industrial yeast Schwanniomyces occidentalis (formerly Schwanniomyces castellii). The transformation system is based on ade2 mutants of S. occidentalis deficient for phosphoribosylaminoimidazole carboxylase that were generated by mutagenesis. As a selectable marker, we isolated and characterized the S. occidentalis ADE2 gene by complementation in an ade2 strain of Saccharomyces cerevisiae. S. occidentalis was transformed with the recombinant plasmid pADE, consisting of a 4.5-kilobase-pair (kbp) DNA fragment from S. occidentalis containing the ADE2 gene inserted into the S. cerevisiae expression vector pYcDE8 by a modification of the spheroplasting procedure of Beggs (J. D. Beggs, Nature [London] 275:104-108, 1978). Intact plasmids were recovered in Escherichia coli from whole-cell lysates of ADE+ transformants, indicating that plasmids were replicating autonomously. High-molecular-mass species of pADE2 were found by Southern hybridization analysis of intact genomic DNA preparations. The shift to higher molecular mass of these plasmids during electrophoresis in the presence ethidium bromide after exposure to shortwave UV suggests that they exist in a supercoiled form in the transformed host. Subclones of the 4.5-kbp insert indicated that ADE2-complementing activity and sequences conferring autonomous replication in S. occidentalis were located within a 2.7-kbp EcoRI-SphI fragment. Plasmids containing this region cloned into the bacterial vector pUC19 complemented ade2 mutants of S. occidentalis with efficiencies identical to those of the original plasmid pADE.


A two-phase model of resource allocation in visual working memory.
Two broad theories of visual working memory (VWM) storage have emerged from current research, a discrete slot-based theory and a continuous resource theory. However, neither the discrete slot-based theory or continuous resource theory clearly stipulates how the mental commodity for VWM (discrete slot or continuous resource) is allocated. Allocation may be based on the number of items via stimulus-driven factors, or it may be based on task demands via voluntary control. Previous studies have obtained conflicting results regarding the automaticity versus controllability of such allocation. In the current study, we propose a two-phase allocation model, in which the mental commodity could be allocated only by stimulus-driven factors in the early consolidation phase. However, when there is sufficient time to complete the early phase, allocation can enter the late consolidation phase, where it can be flexibly and voluntarily controlled according to task demands. In an orientation recall task, we instructed participants to store either fewer items at high-precision or more items at low-precision. In 3 experiments, we systematically manipulated memory set size and exposure duration. We did not find an effect of task demands when the set size was high and exposure duration was short. However, when we either decreased the set size or increased the exposure duration, we found a trade-off between the number and precision of VWM representations. These results can be explained by a two-phase model, which can also account for previous conflicting findings in the literature. (PsycINFO Database Record


Intervention with Formulated Collagen Gel for Chronic Heel Pressure Ulcers in Older Adults with Diabetes.
Chronic pressure ulcers (PrUs), ulcers that fail to progress through the expected phases of wound healing in a timely fashion, are not only a concern for the patients afflicted with them, but are also a significant burden for the long-term-care facilities in which patients reside. The heel is the second most common location for PrUs. Morbidity and mortality rates for heel PrUs, particularly in the diabetic population, are alarming. Therefore, a consistently effective, cost-conscious, and user-friendly topical treatment for heel ulcers would be welcomed by patients and clinicians. This article describes a marked and rapid improvement in wound granulation in 3 older adult patients following weekly treatment for 8 weeks of chronic (≥1-year duration) heel ulcers with an easy-to-use, cost-effective, topical, formulated collagen gel.


A comparison of role conceptions and role deprivation of baccalaureate students in nursing participating in a preceptorship or a traditional clinical program.
In this study, the professional and bureaucratic role conceptions and role deprivation of students participating in a preceptorship program were compared to those in a traditional faculty-supervised clinical group. The role conceptions and role deprivation of nursing faculty and preceptors were also examined. One hundred eighteen students in a two-year upper division baccalaureate program participated in this study. The Corwin Nursing Role Conception tool was administered. Results indicated no differences in role conceptions or role deprivation in students participating in the preceptorship program and those who did not. There were no differences in the developmental pattern of role conception and role deprivation during two years of nursing education. Also, nursing faculty had a significantly higher professional role conception and a significantly lower bureaucratic role conception than preceptors but there were no differences in role deprivation between the two groups.


Validation of a Psychological Screening Algorithm for Predicting Spine Surgery Outcomes.
It is well established that psychological factors can affect spine surgery results. A widely utilized presurgical psychological screening (PPS) algorithm that combines established psychosocial risk factors to determine patients' likelihood of achieving successful spine surgery results is evaluated in this study. Patients (n = 603) underwent a PPS, including a diagnostic interview, psychometric testing, and review of medical records. The evaluator completed a PPS algorithm for patients, placing them into one of five prognosis categories, ranging from excellent to poor. For analysis purposes, these categories were collapsed into three prognosis groups: Excellent, Good, and Fair to Very Poor. Patients classified as having an Excellent prognosis achieved the best outcomes following surgery, whereas those in the Fair to Very Poor category obtained the worst results. Analyses of specific components of the PPS algorithm demonstrated that algorithm items were modestly associated with reduced spine surgery results. Implications for presurgical assessments of spine surgery candidates are discussed.


[Enhancing ethanol production using thermophilic yeast by response surface methodology].
We optimized the conditions of simultaneous saccharification and fermentation (SSF) from cassava flour into high-concentration ethanol by thermophilic yeast GXASY-10. Based on the single factor experiment, we screened the important parameters by Plackeet-burman design. We used the path of steepest ascent to approach to the biggest region of ethanol production subsequently. Then, we obtained the optimum values of the parameters by Box-Behnken design. The results showed that the important parameters were the liquefaction time, glucosidase dosages and initial concentration of cassava flour (substrate). The optimum technical conditions were as follows: liquefaction time 35 min, glucosidase dosages 1.21 AGU/g substrate and initial substrate concentration 37.62%. Under such optimum conditions, the ethanol yield of 20 L fermentor reached 16.07% (V/W) after 48 h fermentation at 37 degrees C and 100 r/min. The ethanol content increased 33% than that under the original condition.


The effect of kangaroo mother care or skin-to-skin contact on infant vital signs: A systematic review and meta-analysis.
It has been reported that kangaroo mother care/skin-to-skin contact immediately after birth facilitates the newborn's physiological and psychological adaptation to extrauterine life. To examine the effect of kangaroo mother care/skin-to-skin contact on infants' body temperature, oxygen saturation, respiratory rate and heart rate. Systematic review and meta-analysis. PubMed, ScienceDirect, SpringerLink, Wiley Online Library and Taylor & Francis Online were searched for the period 1 January 2015 to 30 November 2021 for studies published in the English language. The methodological quality of articles was assessed using the modified Jadad scale and the Newcastle-Ottawa scale. Effect size calculations were made using the fixed effects and random effects models. This meta-analysis included 13 studies, with a total of 891 infants. Kangaroo mother care/skin-to-skin contact was effective for maintaining infants' body temperature (p = 0.000). Infants' heart rate decreased (p = 0.015) and oxygen saturation was higher (p = 0.040) following kangaroo mother care/skin-to-skin contact. Kangaroo mother care/skin-to-skin contact did not affect infants' respiratory rate (p = 0.896), but infants' respiratory rate decreased after kangaroo mother care/skin-to-skin contact (p = 0.047). Kangaroo mother care/skin-to-skin contact is effective for improving the vital signs of newborns. Kangaroo mother care/skin-to-skin contact is recommended for all neonates, and standardization of this approach would be beneficial.


Temporal profile of cortical perfusion and microcirculation after controlled cortical impact injury in rats.
Impaired cerebral perfusion contributes to evolving posttraumatic tissue damage. Spontaneous reversibility of reduced perfusion within the first days after injury could make a persisting impact on secondary tissue damage less likely and needs to be considered for possible therapeutic approaches. The present study was designed to characterize the temporal profile and impact of trauma severity on cortical perfusion and microcirculation during the first 48 h after controlled cortical impact injury (CCI). In 10 rats, pericontusional cortical perfusion and microcirculation using laser Doppler flowmetry (LDF) and orthogonal polarization spectral (OPS) imaging were assessed before, and at 4, 24, and 48 h after CCI. Influence of trauma severity was studied by varying the penetration depth of the impactor rod (0.5 vs. 1 mm), thereby inducing a less and a more severe contusion. Mean arterial blood pressure (MABP), arterial blood gases, and blood glucose were monitored. With unchanged MABP and paCO2, cortical perfusion and microcirculation were significantly impaired during the first 48 h following CCI. Hypoperfusion observed at 4 h related to vasoconstriction and microcirculatory stasis preceded a long-lasting phase of hyperperfusion at 24 and 48 h reflected by vasodilation and increased flow velocity in arterioles and venules. Hyperperfusion was mostly pronounced in rats with a less severe contusion. Following CCI, trauma severity markedly influences changes in pericontusional cortical perfusion and microcirculation. Overall, pericontusional cortical hypoperfusion observed within the early phase preceded a long lasting phase of hyperperfusion up to 48 h after CCI.


Involvement of the myelin-associated inhibitor Nogo-A in early cortical development and neuronal maturation.
Nogo-A is a myelin-associated protein expressed by neurons and myelinating mature oligodendrocytes in the central nervous system. Although most research has focused on the participation of Nogo-A in the prevention of axonal regeneration and plasticity in the adult, little attention has been paid to the putative functions of Nogo-A during embryonic development. Here we examined the general pattern and cell-specific distribution of Nogo-A in the prenatal mouse telencephalon. In addition, we studied the development of the major axon tracts and radial and tangential migration in Nogo-A/B/C knockout mice. The pattern of Nogo-A showed distinct distribution in radial glia and postmitotic neurons, in which it is particularly enriched in developing axons. Similarly, Nogo-A was enriched at the leading process of tangentially migrating interneurons but not detectable in radial migrating neurons. Although a low level of Nogo-A appears to be on the surface of many cortical neurons, most proteins have intracellular localization. In Nogo-deficient background, neurons displayed early polarization and increased branching in vitro, probably reflecting a cell-intrinsic role of Nogo proteins in branching reduction, and early tangential migration was delayed. On the basis of these observations, we propose that Nogo proteins, particularly Nogo-A, are involved in multiple processes during cortical development.


Comparison of two SVD-based color image compression schemes.
Color image compression is a commonly used process to represent image data as few bits as possible, which removes redundancy in the data while maintaining an appropriate level of quality for the user. Color image compression algorithms based on quaternion are very common in recent years. In this paper, we propose a color image compression scheme, based on the real SVD, named real compression scheme. First, we form a new real rectangular matrix C according to the red, green and blue components of the original color image and perform the real SVD for C. Then we select several largest singular values and the corresponding vectors in the left and right unitary matrices to compress the color image. We compare the real compression scheme with quaternion compression scheme by performing quaternion SVD using the real structure-preserving algorithm. We compare the two schemes in terms of operation amount, assignment number, operation speed, PSNR and CR. The experimental results show that with the same numbers of selected singular values, the real compression scheme offers higher CR, much less operation time, but a little bit smaller PSNR than the quaternion compression scheme. When these two schemes have the same CR, the real compression scheme shows more prominent advantages both on the operation time and PSNR.


An approach to conducting epidemiologic research within cooperative clinical trials groups.
Cooperative clinical trials groups offer exciting opportunities for conducting epidemiologic research for several reasons: they facilitate accrual of sufficient numbers of subjects in a short period of time, even for studies of rare diseases; they provide uniform pathologic review and uniform collection of subjects' entry data; and they provide a more representative sample of cases than a single-institution study. Despite these advantages, few epidemiologic studies of etiologic factors have been done through these groups because methods for selecting appropriate control subjects and for obtaining information from geographically scattered subjects have not been available. An approach that can serve as a model for this type of research has been developed. A collaborative case-control study of childhood rhabdomyosarcoma (RMS) with the Intergroup Rhabdomyosarcoma Study (IRS) was recently begun. The study, which is independently funded, evaluates the role of environmental factors in the etiology of RMS. Parents of subjects were interviewed by telephone and control subjects were selected from the same communities as patients by random digit dialing . Interview data are supplemented by information from birth certificates and, for patients, by IRS data. This new methodology permits a large study of a rare tumor in a relatively short period of time.


Circulating interleukin-6 and rheumatoid arthritis: A Mendelian randomization meta-analysis.
Interleukin-6 (IL-6), as a pleiotropic cytokine, has been demonstrated to be closely associated with the pathogenisis of rheumatoid arthritis (RA). However, whether this association is causal or not remains unclear, because of the multifactorial role of IL-6 and related confounding factors. We aimed to evaluate the causal relevance between circulating IL-6 levels and the risk of RA through meta-analytical Mendelian randomization approach. IL-6 gene -174G/C variant was selected as an instrument in this Mendelian randomization meta-analysis. Article identification and data collection were conducted in duplicate and independently by 2 authors. The STATA software was used for data analysis. In total, 15 and 5 articles on the association of the -174G/C variant with RA risk and circulating IL-6 level, respectively, were included. The overall analysis showed that C allelic and GC+CC genotype were significantly with 1.59-fold (95% CI: 1.19-2.14) and 1.63-fold (95% CI: 1.17-2.26) increased risk of developing RA, respectively. Asian populations showed stronger association with 4.55-fold (95% CI: 1.62-12.75), 1.84-fold (95% CI: 1.13-2.99), and 4.69-fold (95% CI: 1.68-13.14) increased RA risk in carriers of -174C allelic, CC, and GC+CC genotype, respectively. Carriers of GC+CC genotype showed significant reduction in the circulating IL-6 level compared with GG carriers (WMD = -0.77; 95% CI: -1.16 to -0.38; P = 0.000) in overall populations. Mendelian randomization presented 6% and 22% increased risk of RA with 0.1 pg/mL reduction of circulating IL-6 level in overall and Asian populations, respectively. This Mendelian randomization meta-analysis demonstrated that the long-term genetically reduced circulating IL-6 level might be causally related to a higher risk of RA, especially in Asian populations.


Proprietary Herbal Extract Downregulates the Gene Expression of IL-1α in HaCaT Cells: Possible Implications Against Nonscarring Alopecia.
Currently while, topical minoxidil and oral finasteride are the only medications approved in androgenetic alopecia (AGA), the cause oriented treatment and immunsupressive treatment are being performed in telogen effluvium (TE) and alopecia areata (AA) respectively. Considering the inflammatory factors in the pathogenesis of these three nonscarring alopecia forms, we have formulated a mixture for topical usage composed of six different herbal extracts (HE) which have already known antiinflammatory and antioxidant features. In addition to performing the phytochemical analysis of HE, we detected the gene expression level of IL-1α, the crucial hair loss mediator, for the putative efficacy in nonscarring alopecia. Cell proliferation assay was performed by XTT reagent. After determination of non-cytotoxic concentration, HaCaT cells were treated with HE. RNA isolations were carried out from both non-treated and treated cell groups by using TRI-reagent. Gene expressions of IL-1α and as control GAPDH were determined by RT-qPCR analysis. Results were represented as "IL-1α/GAPDH Fold Change". HE solution caused statistically significant downregulation of IL-1α gene expressions (p<0.0001), compared to untreated control cells. HE treatment ended up with 0.1900 fold change for IL-1α. IL-1α is a direct growth inhibitory agent in hair follicles and an important actor in the pathogenesis of AGA , TE, and AA. Considering together the vitamins, flavonoids, and trace elements identified in the phytochemical analyses and downregulation of IL-1α in HaCaT cells, our HE may be an auxiliary agent in the therapy of these three nonscarring alopecia forms.


Abdominal compartment syndrome.
The abdominal compartment syndrome (ACS) is a newly appreciated and potentially fatal consequence of increased intra-abdominal pressure. It can be due to either trauma or surgery, as well as numerous medical conditions. Prolonged, unrelieved elevation of intra-abdominal pressure can produce pulmonary compromise, renal impairment, cardiac failure, shock, and death. A high index of suspicion is imperative. Measurement of the intravesical pressure provides a urometric window for detecting and monitoring this condition. Reopening the abdominal incision (decompressive celiotomy) has proven a life-saving intervention. Use of delayed wound closure (staged celiotomy) may prevent development of this condition in high-risk surgical patients. It is urgent that all physicians, and surgeons in particular, be alerted to this potentially lethal complication.


Survey on the levels of 25-hydroxy vitamin D and bone metabolic markers and evaluation of their correlations with osteoporosis in perimenopausal woman in Xi'an region.
It has been accepted that vitamin D (VD) plays an important role in bone metabolism. However, the levels of VD in people of different regions are quite different and there is still no final conclusion on the significant correlation between VD and osteoporosis. 245 cases of peri-menopausal women were collected to study the relationship between VD and osteoporosis in western China. The mean value of 25-hydroxyvitamin D for the participants was 14.39 ng/mL. The average values of parathyroid hormone (PTH), calcium (Ca) and phosphorus (P) were 47.62 pg/mL, 2.26 mmol/L and 1.18 mmol/L, respectively. The average value of bone mineral density (BMD) in lumbar vertebrae was -1.20 SD and that in femoral neck was -0.04 SD. Compared with normal group, PTH of VD deficiency group was significantly increased (P < 0.05), Ca was remarkably decreased (P < 0.01) while the BMD between these two groups showed no significant difference (P > 0.05). VD was in positive correlation with the age (P < 0.01) and Ca (< 0.01) of the participants, negative correlation with PTH (P < 0.01) while no significant correlation with the BMD of lumbar vertebrae and femoral neck (P > 0.05). The risk factors resulting in the occurrence of osteoporosis in the lumbar vertebrae of the participants covered Ca increase (OR = 66.247, P<0.05), age growth (OR = 1.194, P<0.01) and menopause (OR = 2.285, P<0.05). This study has found that the status of VD deficiency showed no significant correlation with the level of BMD, which hinted that independent measurement of the bone metabolic markers, including Ca, P, VD and PTH, was difficult to accurately reflect the status of BMD in peri-menopausal women of this region. It's necessary to combine multi-site bone scanning to diagnose the patients' status of osteoporosis so as to provide reasonable guidance for early clinical prevention and treatment.


Comparison of the arachidonic acid and NADPH-dependent microsomal metabolism of naphthalene and 2-methylnaphthalene and the effect of indomethacin on the bronchiolar necrosis.
Naphthalene and 2-methylnaphthalene cause a highly organo- and species-selective lesion of the pulmonary bronchiolar epithelium in mice. Naphthalene- but not 2-methylnaphthalene-induced pulmonary bronchiolar injury is blocked by prior administration of the cytochrome P-450 monooxygenase inhibitor piperonyl butoxide, thus suggesting that metabolism by enzymes other than the P-450 monooxygenase inhibitor piperonyl butoxide, thus suggesting that metabolism by enzymes other than the P-450 monooxygenases may be important in 2-methylnaphthalene-induced lung injury. Since many of the polycyclic aromatic hydrocarbons are metabolized by the prostaglandin endoperoxide synthetase system and because detectable xenobiotic metabolizing activity has been associated with the prostaglandin synthetases in the Clara cell, the studies reported here were done to compare NADPH-versus arachidonate-dependent metabolism of naphthalene and 2-methylnaphthalene in vitro and to determine whether indomethacin, a potent inhibitor of prostaglandin biosynthesis, was capable of blocking the in vivo toxicity of these two aromatic hydrocarbons. The NADPH-dependent metabolism of naphthalene and 2-methylnaphthalene to covalently bound metabolites in lung or liver microsomal incubations occurred at easily measurable rates. Renal microsomal NADPH-dependent metabolism of either substrate was not detected. The formation of covalently bound naphthalene or 2-methylnaphthalene metabolites was dependent upon NADPH and was inhibited by the addition of reduced glutathione, piperonyl butoxide, and SKF 525A. Covalent binding of radioactivity from [14C]2-methylnaphthalene also was strongly inhibited by incubation in a nitrogen atmosphere or at 2 degree. The arachidonic acid-dependent formation of reactive metabolites from naphthalene or 2-methylnaphthalene was undetectable in microsomal incubations from lung, liver or kidney. Indomethacin, 1 hr before and 6 hr after the administration of 300 mg/kg naphthalene or 2-methylnaphthalene, failed to block the pulmonary bronchiolar injury induced by these aromatic hydrocarbons. These studies suggest that the major enzymes involved in the metabolic activation of naphthalene or 2-methylnaphthalene in vitro are the cytochrome P-450 monooxygenases and that cooxidative metabolism by the prostaglandin synthetases appears to play little role in the formation of reactive metabolites in vitro.


Is childhood physical abuse associated with anxiety disorders among adults?
Several studies have examined the association between childhood physical abuse (CPA) and anxiety disorders with inconsistent results. In order to help clarify this relationship, we investigated the association between CPA and current anxiety disorders while controlling for the following groups of factors: (1) demographics; (2) family background; (3) current socioeconomic status (SES); (4) current stressors; and (5) current mood disorders. Data from the 2005 Canadian Community Health Survey were analyzed. The sample included 12,481 respondents from the Canadian provinces of Manitoba and Saskatchewan. The regional-level response rate was 84%. Fully 7.3% (n = 964) of respondents reported they had been physically abused as a child or adolescent by someone close to them and 4.4% (n = 540) reported they had been diagnosed with an anxiety disorder by a health professional. A significant association between CPA and anxiety disorders was found when controlling for demographic factors, family background, current SES and stressors (OR = 1.61; 95% CI = 1.25, 2.08). The odds of anxiety disorders declined to non-significance when further statistical adjustments were made for current mood disorders. The findings of this research suggest that the relationship between CPA and anxiety may be largely explained by co-morbid mood disorders.


A Philosophical Discussion of the Support of Self-Regulated Learning in Medical Education: The Treasure Hunt Approach Versus the (Dutch) "Dropping" Approach.
Issue: Many current educational approaches are intended to cultivate learners' full (learning) potential by fostering self-regulated learning (SRL), as it is expected that those learners with a high degree of SRL learn more effectively than those with a low degree of SRL. However, these attempts to foster SRL are not always successful. Evidence: We considered complexities related to fostering self-regulated learning by use of an analogy. This analogy was based on two (Dutch) children's games: the treasure hunt (children can find a "treasure" by following directions, completing assignments and/or answering questions) and the dropping (pre-teens are dropped in the woods at nighttime with the assignment to find their way back home). We formulated four interrelated philosophical questions. These questions were not formulated with the intention to provide clear-cut answers, but were instead meant to evoke contemplation about the SRL concept. During this contemplation, the implications of definitional issues regarding SRL were discussed by use of the first question: What are the consequences of the difficulties to explicate what is (not) SRL? The second question (How does SRL relate to autonomy?) touched upon the intricate relationship between SRL and autonomy, by discussing the role of social interaction and varying degrees of instruction when fostering SRL. Next, a related topic was addressed by the third question: How much risk are we willing and able to take when fostering SRL? And finally, the importance of and possibilities to assess SRL were discussed by the fourth question (Should SRL be assessed?). Implications: From our contemplations it has become clear that approaches to foster SRL are often insufficiently aligned with the experience and needs of learners. Instead these approaches are commonly defined by contextual factors, such as misconceptions about SRL and lack of leeway for learners. Consequently, we have used principles that apply to both treasure hunts and droppings, to provide guidelines on how to align one's approach to foster SRL with the educational context and experience and needs of learners.


Steady-state evaluation of two controlled-release theophylline preparations in children.
The absorption profiles of Theolair-SR and Theo-Dur were studied in 23 asthmatic children (mean age 11 years). A 250-mg dose of each product was administered twice a day until steady state was attained (mean, 8 days). Both products maintained adequate theophylline levels over 12 hours, although Theolair-SR gave significantly higher serum levels and a 19% greater extent of theophylline absorption. The mean Cmax-Cmin was also significantly greater for Theolair-SR. Both products should be considered comparable for practical use.


[New bronchodilators and combinations in COPD treatment].
Bronchodilator drugs are widely used therapeutic agents for treatment of asthma and chronic obstructive pulmonary disease (COPD). In order to mantain bronchodilation, both sympathetic system (particularly beta-2 receptors) activation and parasympathetic system inhibition (antimuscarinic effect) mechanisms are utilized. Over 20 years, there were no significant changes in bronchodilator therapy in obstructive pulmonary diseases. In recent years, however, after the development of new ultra long acting bronchodilator drugs, a single dose inhaler treatments per day in the treatment of stable COPD became a current issue. In this review, with the guidence of the current literature, the effects of new beta-2 agonists and anticholinergic bronchodilators will be discussed.


Facebook as communication support for persons with potential mild acquired cognitive impairment: A content and social network analysis study.
Social media has the potential to increase social participation and support for the well-being of individuals with chronic medical conditions. To date, Facebook is the most popular social medium for different types of communication. However, there is a lack of knowledge about the potential use of Facebook as a means of communication for persons with potential Mild Acquired Cognitive Impairment (MACI), a non-progressive mild cognitive impairment after an acquired brain injury. The aim of this study was to explore how persons with potential MACI, specifically persons with perceived brain fatigue after brain injury, communicate through Facebook, to classify the content of the communication and to visualize the frequency and types of interactions. A social network analysis of the interactions between members' and a qualitative content analysis of a whole year's communication of a public Facebook group for Swedish speaking persons (1310 members) with perceived brain fatigue after an illness or injury to the brain were performed. The results showed how members use social media technology and Facebook as a means for communication and support for their condition. Individual group members showed very different patterns of communication and interactions. However, for the group as a whole, the most frequent topics in their communication were related to informational support and banter in posts, and socialization in comments. The findings also showed that the majority of members only communicated with few other members and had few direct communications. The most used communication feature of Facebook was likes in form of "thumbs-up". This study indicated that social media and in this case Facebook is used for communication and social support by persons with potential MACI, and revealed that their communication behavior is similar to the healthy population. Further studies relating specific cognitive problems of the participants to the use of social media would provide more reliable results for this specific group.


Do I Buy It? How AIDET™ Training Changes Residents' Values about Patient Care.
Acquiring communication and interpersonal skills is an important part of providing patient-centered care and improving patient satisfaction. This study explores whether residents' own values about patient communication can be influenced by training. As part of service excellence, a three-hour communication skills training in AIDET™ (Acknowledge, Introduce, Duration, Explanation, Thank You) was delivered to first and second Post-Graduate Year (PGY) residents (n = 123). A survey was designed to measure the value of patient communication and administered pre/post communication skills training. Residents' scores about communication values improved significantly for all areas pre- to post-training for patient communication skills (p<0.04). After training, there was little difference by medical specialty, other than surgical specialties, which showed the greatest increase in valuing requesting permission (p=0.034). Gender was also not associated with differences in values, except men showed a greater increase in valuing sitting down (p=0.021) and introductions (p=0.005) than women who already valued these specific behaviors prior to training. Residents value communication, and AIDET™ training is a useful tool to increase the values of good communication and interpersonal skills to enhance service excellence.


[Advances in study on the nature products of anti-myocardial ischemia].
Ischemic heart disease (IHD) is a kind of severe cardiovascular disease. It has become one of the main reasons resulting in people's death. So it is very pressing to explore some active substances with anti-myocardial ischemia physiological activity. It is important to develop some safe and effective drugs. In this paper we review the advance in study on the source, chemical ingredient and pharmacological action of the anti-myocardial ischemia of thirty kinds of nature products.


[A case of primary signet ring cell carcinoma of the breast].
A rare case of primary signet ring cell carcinoma of the breast is reported. The patient was a 54-year-old unmarried female (G 0, P 0, AB 0) with a several months' history of inflammatory reactions, such as infection, erosion, and a swelling of her entire left breast. She died of this disease in 6 months despite an operation and combined chemotherapy (CMF). Her serum CEA level had well reflected the course of her treatment. Histopathologically, a primary lesion and axillary lymph nodes were found to be filled with typical signet ring cells, whose cytoplasm showed positive staining for PAS and Alcian blue stains as well as CEA. This case, both clinically and histopathologically, displayed the peculiar characteristics of signet ring cell carcinoma, which differs from other types of breast cancer.


Molecular epidemiology and susceptibility profiles of Clostridium difficile in New Zealand, 2009.
The aim of this study was to provide baseline information on the molecular epidemiology and the antimicrobial susceptibility of Clostridium difficile (C. difficile) clinical isolates from patients throughout New Zealand. Faecal specimens that were C. difficile-toxin positive by EIA assay were cultured for C. difficile. Antimicrobial susceptibility testing was carried out using the agar dilution minimum inhibitory concentration method. The following antibiotics were tested: penicillin, piperacillin/tazobactam, vancomycin, ciprofloxacin, moxifloxacin, clindamycin, clarithromycin, meropenem and metronidazole. Molecular typing by PCR-ribotyping was performed on all isolates. C. difficile was isolated from 108 of 159 submitted faecal specimens. After excluding the repeats, there were 101 isolates from 97 patients. Most isolates were fully susceptible to the range of antibiotics tested. Thirty-two PCR-ribotypes were identified among the 101 isolates. The most common ribotypes were 014 (18 isolates), 002 (11) and 005 (10). No PCR-ribotype 027 isolates were identified, but one isolate of another hypervirulent strain, PCR-ribotype 078, was identified. There is a wide range of C. difficile PCR-ribotypes circulating in New Zealand and antimicrobial resistance is uncommon. Ongoing surveillance for hypervirulent strains of C. difficile is essential to prevent the dissemination of these strains within New Zealand hospitals.


Comparison of Different Hypotheses Regarding the Spread of Alzheimer's Disease Using Markov Random Fields and Multimodal Imaging.
Alzheimer's disease (AD) is characterized by a cascade of pathological processes that can be assessed in vivo using different neuroimaging methods. Recent research suggests a systematic sequence of pathogenic events on a global biomarker level, but little is known about the associations and dependencies of distinct lesion patterns on a regional level. Markov random fields are a probabilistic graphical modeling approach that represent the interaction between individual random variables by an undirected graph. We propose the novel application of this approach to study the interregional associations and dependencies between multimodal imaging markers of AD pathology and to compare different hypotheses regarding the spread of the disease. We retrieved multimodal imaging data from 577 subjects enrolled in the Alzheimer's Disease Neuroimaging Initiative. Mean amyloid load (AV45-PET), glucose metabolism (FDG-PET), and gray matter volume (MRI) were calculated for the six principle nodes of the default mode network- a functional network of brain regions that appears to be preferentially targeted by AD. Multimodal Markov random field models were developed for three different hypotheses regarding the spread of the disease: the "intraregional evolution model", the "trans-neuronal spread" hypothesis, and the "wear-and-tear" hypothesis. The model likelihood to reflect the given data was evaluated using tenfold cross-validation with 1,000 repetitions. The most likely graph structure contained the posterior cingulate cortex as main hub region with edges to various other regions, in accordance with the "wear-and-tear" hypothesis of disease vulnerability. Probabilistic graphical models facilitate the analysis of interactions between several variables in a network model and therefore afford great potential to complement traditional multiple regression analyses in multimodal neuroimaging research.


PRRT2 mutations are related to febrile seizures in epileptic patients.
Previous studies reported that the proline-rich transmembrane protein 2 (PRRT2) gene was identified to be related to paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions with PKD, PKD with migraine and benign familial infantile epilepsy (BFIE). The present study explores whether the PRRT2 mutation is a potential cause of febrile seizures, including febrile seizures plus (FS+), generalized epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS); thus, it may provide a new drug target for personalized medicine for febrile seizure patients. We screened PRRT2 exons in a cohort of 136 epileptic patients with febrile seizures, including FS+, GEFS+ and DS. PRRT2 genetic mutations were identified in 25 out of 136 (18.4%) febrile seizures in epileptic patients. Five loss-of-function and coding missense mutations were identified: c.649delC (p.R217Efs*12), c.649_650insC (p.R217Pfs*8), c.412C>G (p.Pro138Ala), c.439G>C (p.Asp147His) and c.623C>A (p.Ser208Tyr). PRRT2 variants were probably involved in the etiology of febrile seizures in epileptic patients.


Extended high-frequency audiometry in research and clinical practice.
Audiometric testing in research and in clinical settings rarely considers frequencies above 8 kHz. However, the sensitivity of young healthy ears extends to 20 kHz, and there is increasing evidence that testing in the extended high-frequency (EHF) region, above 8 kHz, might provide valuable additional information. Basal (EHF) cochlear regions are especially sensitive to the effects of aging, disease, ototoxic drugs, and possibly noise exposure. Hence, EHF loss may be an early warning of damage, useful for diagnosis and for monitoring hearing health. In certain environments, speech perception may rely on EHF information, and there is evidence for an association between EHF loss and speech perception difficulties, although this may not be causal: EHF loss may instead be a marker for sub-clinical damage at lower frequencies. If there is a causal relation, then amplification in the EHF range may be beneficial if the technical difficulties can be overcome. EHF audiometry in the clinic presents with no particular difficulty, the biggest obstacle being lack of specialist equipment. Currently, EHF audiometry has limited but increasing clinical application. With the development of international guidelines and standards, it is likely that EHF testing will become widespread in future.


Direct core materials.
There are many materials that can be used for direct-placement cores. Although the scientific evidence is incomplete, some materials are better suited to this task than others. This article provides an overview of direct-placement core materials and highlights what clinicians should consider when assessing a new product.


Bactericidal activity of medicinal plants, employed for the treatment of gastrointestinal ailments, against Helicobacter pylori.
Helicobacter pylori infection plays a crucial role in the pathogenesis of peptic ulcer, and gastric cancer. The current PPI-based triple regimens for the eradication of Helicobacter pylori faces uprising resistance problem demanding for the search of novel candidates. Medicinal plants have always been a source of lead compounds for drug discovery. In the present study, we evaluated the anti-Helicobacter pylori activity of 50 commonly used Unani (traditional) medicine plants from Pakistan that are extensively utilized for the cure of gastrointestinal disorders to explore the natural source for pilot compounds against Helicobacter pylori. Total seven clinical isolates and one standard strain were employed to examine the bactericidal effects of medicinal plants. Helicobacter pylori was isolated from the antral biopsy specimens and confirmed through the standard microbiology procedures. Minimum bactericidal concentration (MBC) of the active plants was determined at the concentration range from 7.8 to 500 microg/ml. Among the herbs evaluated, more than 50% inhibited the growth of eight strains at the concentration of 500 microg/ml. The 70% aqueous-ethanol extracts of Curcuma amada Roxb., Mallotus phillipinesis (Lam) Muell., Myrisctica fragrans Houtt., and Psoralea corylifolia L. demonstrated strong anti-Helicobacter pylori activity with MBC value ranged from 15.6 to 62.5 microg/ml. The most potent bactericidal activity was exhibited by Mallotus phillipinesis (Lam) Muell. which completely killed the bacteria at the concentration of 15.6-31.2 microg/ml. The results revealed significant anti-Helicobacter pylori activity of medicinal plants which could be the potential source of new bactericidal agents.


On the nature and scope of featural representations of word meaning.
Behavioral experiments and a connectionist model were used to explore the use of featural representations in the computation of word meaning. The research focused on the role of correlations among features, and differences between speeded and untimed tasks with respect to the use of featural information. The results indicate that featural representations are used in the initial computation of word meaning (as in an attractor network), patterns of feature correlations differ between artifacts and living things, and the degree to which features are intercorrelated plays an important role in the organization of semantic memory. The studies also suggest that it may be possible to predict semantic priming effects from independently motivated featural theories of semantic relatedness. Implications for related behavioral phenomena such as the semantic impairments associated with Alzheimer's disease (AD) are discussed.


Tuning reactivity of Fischer-Tropsch synthesis by regulating TiOx overlayer over Ru/TiO2 nanocatalysts.
The activity of Fischer-Tropsch synthesis (FTS) on metal-based nanocatalysts can be greatly promoted by the support of reducible oxides, while the role of support remains elusive. Herein, by varying the reduction condition to regulate the TiOx overlayer on Ru nanocatalysts, the reactivity of Ru/TiO2 nanocatalysts can be differentially modulated. The activity in FTS shows a volcano-like trend with increasing reduction temperature from 200 to 600 °C. Such a variation of activity is characterized to be related to the activation of CO on the TiOx overlayer at Ru/TiO2 interfaces. Further theoretical calculations suggest that the formation of reduced TiOx occurs facilely on the Ru surface, and it involves in the catalytic mechanism of FTS to facilitate the CO bond cleavage kinetically. This study provides a deep insight on the mechanism of TiOx overlayer in FTS, and offers an effective approach to tuning catalytic reactivity of metal nanocatalysts on reducible oxides.


Platelet storage and transfusions: new concerns associated with an old therapy.
Platelet transfusion has long been practiced with rudimentary knowledge about optimal storage conditions and their implications for efficacy and, particularly, safety. Recent concerns about complications such as inflammation, thrombosis and altered recipient immunity have been raised about platelet transfusion. This review will discuss recent important findings that have raised these issues about platelet transfusion associated morbidity, mortality and the possible role of platelet storage in these associations.


Antibiotic prophylaxis for operative vaginal delivery.
Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics are prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum and/or forceps deliveries. We searched the Cochrane Pregnancy and Childbirth Group trials register (November 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003) and MEDLINE (1966 to November 2003). All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Four reviewers assessed trial eligibility and methodological quality. Two reviewers extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all reviewers. We assessed methodological quality of the included trial using the standard Cochrane criteria and the CONSORT statement of randomised controlled trials. We calculated the relative risks using a fixed effect model and all the reviewers interpreted and discussed the results. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. This trial identified only two out of the nine outcomes specified in this review. It reported seven women with endomyometritis in the group given no antibiotic and none in prophylactic antibiotic group. This difference did not reach statistical significance, but the relative risk reduction was 93% (relative risks 0.07; 95% confidence interval (CI) 0.00 to 1.21). There was no difference in the length of hospital stay between the two groups (weighted mean difference 0.09 days; 95% CI -0.23 to 0.41). The data were too few and of insufficient quality to make any recommendations for practice. Future research on antibiotic prophylaxis for operative vaginal delivery is needed to conclude whether it is useful for reducing postpartum morbidity.


The comparison of the performance of four whole genome amplification kits on ion proton platform in copy number variation detection.
With the development and clinical application of genomics, more and more concern is focused on single-cell sequencing. In the process of single-cell sequencing, whole genome amplification is a key step to enrich sample DNA. Previous studies have compared the performance of different whole genome amplification (WGA) strategies on Illumina sequencing platforms, but there is no related research aimed at Ion Proton platform, which is also a popular next-generation sequencing platform. Here by amplifying cells from six cell lines with different karyotypes, we estimated the data features of four common commercial WGA kits (PicoPLEX WGA Kit, GenomePlex Single Cell Whole Genome Amplification Kit, MALBAC Single Cell Whole Genome Amplification Kit, and REPLI-g Single Cell Kit), including median absolute pairwise difference, uniformity, reproducibility, and fidelity, and examined their performance of copy number variation detection. The results showed that both MALBAC and PicoPLEX could yield high-quality data and had high reproducibility and fidelity; and as for uniformity, PicoPLEX was slightly superior to MALBAC.


Magnetic compression anastomosis for patients with a disconnected bile duct after living-donor related liver transplantation: a pilot study.
We present the use of the magnetic compression anastomosis (MCA) technique for treatment of disconnected bile duct after living-donor related liver transplantation (LDLT) using the recently introduced through-the-scope magnet. The MCA technique was used in patients with disconnected bile duct who could not be treated with either percutaneous or endoscopic procedures. All patients already had a percutaneous external biliary drainage catheter before the procedure. The magnet was placed percutaneously into the proximal side of the obstruction by pushing a 5-Fr catheter over a guidewire. Concurrently, endoscopic retrograde cholangiopancreatography (ERCP) including endoscopic papillary sphincterotomy was performed. The sister magnet was then carefully advanced to the opposite side of the obstruction with a 5-Fr catheter over a guidewire. After the confirmation of biliary recanalization, a guidewire was passed through the stricture and a percutaneous dilation of the stricture was performed with a balloon-tipped catheter. Endoscopic balloon dilation of the stricture, insertion of two plastic stents and the removal of the internal drainage catheter were performed during the first ERCP session. Stent exchange and multiple side-by-side stent placements were planned at regular intervals (3 monthly) for all patients. A total of six LDLT patients with disconnected bile duct (aged 37 - 68, four men) underwent the MCA technique between September 2014 and July 2015. Biliary recanalization was achieved 13 - 42 days after the magnet placement procedure. The success rate of the procedure was 100 %. The MCA technique using a small magnet (diameter 2.4 mm) is effective and useful in LDLT patients with disconnected bile duct.


Training-Associated Emotional Arousal Shapes Endocannabinoid Modulation of Spatial Memory Retrieval in Rats.
Variations in environmental aversiveness influence emotional memory processes in rats. We have previously shown that cannabinoid effects on memory are dependent on the stress level at the time of training as well as on the aversiveness of the environmental context. Here, we investigated whether the hippocampal endocannabinoid system modulates memory retrieval depending on the training-associated arousal level. Male adult Sprague Dawley rats were trained on a water maze spatial task at two different water temperatures (19°C and 25°C) to elicit either higher or lower stress levels, respectively. Rats trained under the higher stress condition had better memory and higher corticosterone concentrations than rats trained at the lower stress condition. The cannabinoid receptor agonist WIN55212-2 (10-30 ng/side), the 2-arachidonoyl glycerol (2-AG) hydrolysis inhibitor JZL184 (0.1-1 μg/side), and the anandamide (AEA) hydrolysis inhibitor URB597 (10-30 ng/side) were administered bilaterally into the hippocampus 60 min before probe-trial retention testing. WIN55212-2 or JZL184, but not URB597, impaired probe-trial performances only of rats trained at the higher stressful condition. Furthermore, rats trained under higher stress levels displayed an increase in hippocampal 2-AG, but not AEA, levels at the time of retention testing and a decreased affinity of the main 2-AG-degrading enzyme for its substrate. The present findings indicate that the endocannabinoid 2-AG in the hippocampus plays a key role in the selective regulation of spatial memory retrieval of stressful experience, shedding light on the neurobiological mechanisms involved in the impact of stress effects on memory processing. Endogenous cannabinoids play a central role in the modulation of memory for emotional events. Here we demonstrate that the endocannabinoid 2-arachidonoylglycerol in the hippocampus, a brain region crucially involved in the regulation of memory processes, selectively modulates spatial memory recall of stressful experiences. Thus, our findings provide evidence that the endocannabinoid 2-arachidonoylglycerol is a key player in mediating the impact of stress on memory retrieval. These findings can pave the way to new potential therapeutic intervention for the treatment of neuropsychiatric disorders, such as post-traumatic stress disorder, where a previous exposure to traumatic events could alter the response to traumatic memory recall leading to mental illness.


[Lactation-induced amenorrhea as birth control method].
Improving access to quality care in family planning, a recent document of the World Health Organization, reviews the epidemiological and clinical evidence relevant to medical eligibility of well established contraceptive methods. Breastfeeding is widely regarded as unreliable for individual contraception. The document, however, argues that the lactational amenorrhoea method (LAM) is a safe and effective family planning method. Worldwide, LAM is the most important way of fertility regulation and its efficacy is confirmed in many studies, with a 2% risk of pregnancy in the first six months after birth. Taking into account certain well defined conditions (frequent feedings, no supplementary feeding before 4-6 months, method only to be used in the absence of menstruation), LAM can be relied on for contraceptive protection for up to 1 year post partum.


Validation of the Pangao PG-800A11 wrist device assessed according to the European Society of Hypertension and the British Hypertension Society protocols.
The objective of this study was to determine the accuracy of the Pangao PG-800A11 wrist blood pressure monitor according to the European Society of Hypertension International Protocol (ESH-IP) revision 2010 and the protocol of the British Hypertension Society (BHS). The device evaluations were performed in 85 participants, 33 of whom were included according to the ESH-IP revision 2010 and 52 of whom were included on the basis of the requirements of the BHS protocol. The validation procedure and data analysis followed the protocols precisely. The device achieved an A/A grading for the BHS protocol and passed all phases of the ESH-IP revision 2010 protocol. The mean difference ±SD for the ESH and BHS protocols, respectively, was -0.6±4.5 and -0.8±6.2 mmHg for systolic pressure and 1.2±4.6 and -0.5±5.1 mmHg for diastolic pressure. The device maintained its A/A grading throughout the low, medium, and high-pressure ranges. The Pangao PG-800A11 wrist blood pressure monitor passed all requirements of the ESH-IP revision 2010 and achieved A/A grade of the BHS protocol in an adult population.


Hierarchical three-dimensional microbattery electrodes combining bottom-up self-assembly and top-down micromachining.
The realization of next-generation portable electronics and integrated microsystems is directly linked with the development of robust batteries with high energy and power density. Three-dimensional micro- and nanostructured electrodes enhance energy and power through higher surface area and thinner active materials, respectively. Here, we present a novel approach for the fabrication of hierarchical electrodes that combine benefits of both length scales. The electrodes consist of self-assembled, virus-templated nanostructures conformally coating three-dimensional micropillars. Active battery material (V(2)O(5)) is deposited using atomic layer deposition on the hierarchical micro/nanonetwork. Electrochemical characterization of these electrodes indicates a 3-fold increase in energy density compared to nanostructures alone, in agreement with the surface area increase, while maintaining the high power characteristics of nanomaterials. Investigation of capacity scaling for varying active material thickness reveals underlying limitations in nanostructured electrodes and highlights the importance of our method in controlling both energy and power density with structural hierarchy.


Payor Reform Opportunities for Spine Surgery: Part II: The Potential Emergence of Population Health.
The pressures on spine surgery to adopt value-based reimbursement models are being seen in the increased implementation of bundled payment strategies. Given that bundled payment models typically link payments to the initiation of the surgical episode in question, despite their potential cost-saving attributes, financial incentives remain tied to the volume of services being provided. As payors and policy makers look to find savings by focusing on waste and variation of care, more comprehensive models such population health strategies are now being develop and deployed. The clinical delivery and cost variation currently seen in spine health management make spine surgery an acute target of such population health strategies. Spine surgeons should understand the forces driving such changes and the opportunities to optimize performance within them.


Herman Boerhaave, the Dutch Hippocrates, a Forgotten Father of Medicine.
In today's medical community, when people say the name Herman Boerhaave, most assimilate it to Boerhaave syndrome. His influence on medicine is seen every day in hospitals around the world. His methodologies revolutionized medical education and the way physicians approach the examination of patients. It has been said that during the Age of Reason, he was the "Bearer of the Enlightenment of Medicine." He is a forgotten father of medicine. To preserve medical history, educators should give students a brief summary of the contributors to medicine to remind us how much of their lives they gave to further medical knowledge.


Umbilical artery ultrasound haemodynamics combined with serum adiponectin levels can aid in predicting adverse pregnancy outcomes in patients with severe pre-eclampsia.
Severe pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. This retrospective study explored pregnancy outcome predictive values of umbilical artery Doppler with serum adiponectin in severe pre-eclampsia. Fasting elbow venous blood was collected from 118 severe pre-eclampsia patients [maternal systolic pressure ≥ 160 mmHg and/or diastolic pressure ≥ 110 mmHg + minimal proteinuria, 56; mild hypertension + heavy proteinuria (≥2 g/24 h or random urinary protein ≥ 2+), 42; no proteinuria but new-onset hypertension + diseases of heart/lung/liver/kidney/other organs or abnormalities in blood/digestive/nervous systems, placental foetus involved, 20] and 90 controls (18.5-24.9 kg/m2) in the first morning of admission. Serum adiponectin and resistance/pulsatility indexes were separately measured and correlatively analysed by Pearson's coefficient analysis. Adverse outcomes included maternal primary postpartum haemorrhage and placental abruption, neonatal asphyxia, low birth weight, foetal distress, foetal growth restriction. In severe pre-eclampsia, serum adiponectin (downregulated) was negatively-correlated with resistance/pulsatility indexes (upregulated). The area under the curve of umbilical artery Doppler with serum adiponectin for predicting adverse outcomes of severe pre-eclampsia was 0.6545 (specificity 60.27%, sensitivity 60.00%). In conclusion, umbilical artery Doppler with serum adiponectin predicts adverse pregnancy outcomes in severe pre-eclampsia.Impact statementWhat is already known on this subject? Sad levels were lowered in sPE patients. UA ultrasound hemodynamic parameters can predict adverse pregnancy outcomes.What do the results of this study add? Our study revealed that ultrasonic hemodynamic indexes of UA combined with Sad levels had better efficacy in predicting pregnancy outcomes in patients with sPE, and our study is expected to improve the accuracy of clinical prediction of adverse outcomes in sPE patients.What are the implications of these findings for clinical practice and/or further research? Through the combined detection of multiple indicators of the foetus in the mother, our study expects to be able to monitor and predict the growth of the foetus in the mother more accurately in clinical practice, avoid excessive intervention or untimely intervention, and reduce the incidence of perinatal adverse pregnancy outcomes.


A fluctuation-driven mechanism for slow decision processes in reverberant networks.
The spike activity of cells in some cortical areas has been found to be correlated with reaction times and behavioral responses during two-choice decision tasks. These experimental findings have motivated the study of biologically plausible winner-take-all network models, in which strong recurrent excitation and feedback inhibition allow the network to form a categorical choice upon stimulation. Choice formation corresponds in these models to the transition from the spontaneous state of the network to a state where neurons selective for one of the choices fire at a high rate and inhibit the activity of the other neurons. This transition has been traditionally induced by an increase in the external input that destabilizes the spontaneous state of the network and forces its relaxation to a decision state. Here we explore a different mechanism by which the system can undergo such transitions while keeping the spontaneous state stable, based on an escape induced by finite-size noise from the spontaneous state. This decision mechanism naturally arises for low stimulus strengths and leads to exponentially distributed decision times when the amount of noise in the system is small. Furthermore, we show using numerical simulations that mean decision times follow in this regime an exponential dependence on the amplitude of noise. The escape mechanism provides thus a dynamical basis for the wide range and variability of decision times observed experimentally.


Dactoscopy in Human Identification: A Retrospective Study in Bhubaneswar City.
Anthropometry, fingerprints, age estimation, gender determination, blood types, DNA, and dental features are examples of traditional techniques for identifying a person. The present study aimed toward observing the patterns of fingerprints and their reliability toward human identification. A retrospective study was conducted in a tertiary care unit in Bhubaneswar city. Fingerprints were recorded, and the individual identification mark was noted for each individual. Reporting of the patterns was done. Sir Henry Galton's classification was used to study the fingerprint patterns. IBM Statistical Package for Social Sciences was used for the statistical analysis. Type A was the most common type seen for the right-hand little finger. Type A was the most common type seen for the left-hand little finger; Type C was the most common type seen for the left-hand ring finger. Statistically significant correlations between gender and dermatoglyphics were found, supporting their usage as trustworthy forensic evidence.


Single-Plane Magnetically Focused Elongated Small Field Proton Beams.
We previously performed Monte Carlo simulations of magnetically focused proton beams shaped by a single quadrapole magnet and thereby created narrow elongated beams with superior dose delivery characteristics (compared to collimated beams) suitable for targets of similar geometry. The present study seeks to experimentally validate these simulations using a focusing magnet consisting of 24 segments of samarium cobalt permanent magnetic material adhered into a hollow cylinder. Proton beams with properties relevant to clinical radiosurgery applications were delivered through the magnet to a water tank containing a diode detector or radiochromic film. Dose profiles were analyzed and compared with analogous Monte Carlo simulations. The focused beams produced elongated beam spots with high elliptical symmetry, indicative of magnet quality. Experimental data showed good agreement with simulations, affirming the utility of Monte Carlo simulations as a tool to model the inherent complexity of a magnetic focusing system. Compared to target-matched unfocused simulations, focused beams showed larger peak to entrance ratios (26% to 38%) and focused simulations showed a two-fold increase in beam delivery efficiency. These advantages can be attributed to the magnetic acceleration of protons in the transverse plane that tends to counteract the particle outscatter that leads to degradation of peak to entrance performance in small field proton beams. Our results have important clinical implications and suggest rare earth focusing magnet assemblies are feasible and could reduce skin dose and beam number while delivering enhanced dose to narrow elongated targets (eg, in and around the spinal cord) in less time compared to collimated beams.


Postirradiation malignant fibrous histiocytoma of the trachea.
A 77-yr-old woman presented with a malignant fibrous histiocytoma (MFH) of the trachea 11 yr after right subtotal thyroidectomy and delivery of 5,400 rads to the neck for infiltrating papillary thyroid carcinoma. The tumor developed in the irradiated area. Postirradiation MFH tends to occur in subcutaneous tissues, and is rare in lung parenchyma or airways.


Lateral approach to the lumbar spine: The utility of an access surgeon.
Lateral lumbar interbody fusions (LLIFs) utilize a retroperitoneal approach that avoids the intraperitoneal organs and manipulation of the anterior vasculature encountered in anterior approaches to the lumbar spine. The approach was championed by spinal surgeons; however, general/vasculature surgeons may be more comfortable with the approach. The objective of this study was to compare short-term outcomes following LLIF procedures based on whether a spine surgeon or access surgeon performed the approach. We retrospectively identified all one- to two-level LLIFs at a tertiary care center from 2011 to 2021 for degenerative spine disease. Patients were divided into groups based on whether a spine surgeon or general surgeon performed the surgical approach. The electronic medical record was reviewed for hospital readmissions and complication rates. We identified 239 patients; of which 177 had approaches performed by spine surgeons and 62 by general surgeons. The spine surgeon group had fewer levels with posterior instrumentation (1.40 vs. 2.00; P < 0.001) and decompressed (0.94 vs. 1.25, P = 0.046); however, the two groups had a similar amount of two-level LLIFs (29.9% vs. 27.4%, P = 0.831). This spine surgeon approach group was found to have shorter surgeries (281 vs. 328 min, P = 0.002) and shorter hospital stays Length of Stay (LOS) (3.1 vs. 3.6 days, P = 0.019); however, these differences were largely attributed to the shorter posterior fusion construct. On regression analysis, there was no statistical difference in postoperative complication rates whether or not an access surgeon was utilized (P = 0.226). Similar outcomes may be seen regardless of whether a spine or access surgeon performs the approach for an LLIF.


Stress responsive mitochondrial proteins in Arabidopsis thaliana.
In the last decade plant mitochondria have emerged as a target, sensor and initiator of signalling cascades to a variety of stress and adverse growth conditions. A combination of various 'omic profiling approaches combined with forward and reverse genetic studies have defined how mitochondria respond to stress and the signalling pathways and regulators of these responses. Reactive oxygen species (ROS)-dependent and -independent pathways, specific metabolites, complex I dysfunction, and the mitochondrial unfolded protein response (UPR) pathway have been proposed to date. These pathways are regulated by kinases (sucrose non-fermenting response like kinase; cyclin dependent protein kinase E 1) and transcription factors from the abscisic acid-related, WRKY and NAC families. A number of independent studies have revealed that these mitochondrial signalling pathways interact with a variety of phytohormone signalling pathways. While this represents significant progress in the last decade there are more pathways to be uncovered. Post-transcriptional/translational regulation is also a likely determinant of the mitochondrial stress response. Unbiased analyses of the expression of genes encoding mitochondrial proteins in a variety of stress conditions reveal a modular network exerting a high degree of anterograde control. As abiotic and biotic stresses have significant impact on the yield of important crops such as rice, wheat and barley we will give an outlook of how knowledge gained in Arabidopsis may help to increase crop production and how emerging technologies may contribute.


Sitting Time, Physical Activity and Sleep by Work Type and Pattern-The Australian Longitudinal Study on Women's Health.
Data from the Australian Longitudinal Study on Women's Health were used to examine how work was associated with time spent sleeping, sitting and in physical activity (PA), in working women. Young (31-36 years; 2009) and mid-aged (59-64 years; 2010) women reported sleep (categorised as shorter ≤6 h/day and longer ≥8 h/day) and sitting time (work, transport, television, non-work computer, and other; summed for total sitting time) on the most recent work and non-work day; and moderate and vigorous PA (categorised as meeting/not meeting guidelines) in the previous week. Participants reported occupation (manager/professional; clerical/sales; trades/transport/labourer), work hours (part-time; full-time) and work pattern (shift/night; not shift/night). The odds of shorter sleep on work days was higher in both cohorts for women who worked shift or night hours. Longer sitting time on work days, made up primarily of sitting for work, was found for managers/professionals, clerical/sales and full-time workers. In the young cohort, clerical/sales workers and in the mid-aged cohort, full-time workers were less likely to meet PA guidelines. These results suggest multiple behaviour interventions tailored to work patterns and occupational category may be useful to improve the sleep, sitting and activity of working women.


[Characteristics of food anaphylactic reactions to proteins and protein preparations in guinea pigs with different duration of hexenal-induced sleep].
The state of guinea pig sensitization was studied in the direct test in vivo by induction of active food anaphylaxis (FA). The animals were orally sensitized with food allergens: chick ovalbumin (OVA), bovine serum albumin, and protein preparations N 1 and N 2 (PP N 1 and N 2). In guinea pigs with null hexenal-induced sleep (NHS) and long hexenal-induced sleep (LHS), 40 min, the duration of HS is reliably reproduced in repeated testing. The intensity of FA reactions in guinea pigs with NHS was less manifested than in the animals with LHS with both food allergens. Significantly higher allergenic properties of PP N 2 were expressed in the animals with LHS. It was shown that varying anaphylactic sensitivity of guinea pigs in the above groups was not related with different permeability of the gastrointestinal tract of these animals for OVA macromolecules. Possibilities of metabolic validation of increasing anaphylactic sensitivity of guinea pigs with LHS have been considered.


Angiotensin II regulates liver regeneration via type 1 receptor following partial hepatectomy in mice.
Angiotensin II (Ang II) is an important mediator stimulating liver fibrosis after liver injury. However, it is not known whether Ang II plays a role in liver regeneration. Here, we investigate the effects of Ang II type 1 (AT(1)) receptor blocker (ARB), angiotensin-converting enzyme inhibitor (ACEI), systemic infusion of Ang II, and genetic deficiency of the AT(1a) receptor (AT1a-KO) on the hepatic regenerative response to partial hepatectomy (PH) in mice. Administration of ARB (candesartan cilexetil and losartan) or ACEI (enarapril and lisinopril) enhanced 5-bromo-2'-deoxyuridine (BrdU) incorporation into hepatocyte nuclei in remnant liver as well as the restoration of liver weight after PH. Systemic infusion of Ang II (100 ng/kg/min) suppressed the PH-induced BrdU incorporation and the restoration of liver weight. In contrast to Ang II infusion, these hepatic responses to PH were significantly greater in AT1a-KO mice than in wild-type mice. The PH-induced increases in hepatic levels of hepatocyte growth factor (HGF) mRNA and plasma HGF concentrations were greater in candesartan- and enarapril-treated mice or in AT1a-KO mice than in vehicle-treated mice or wild-type mice, respectively, whereas they were less in Ang II-infused mice than in vehicle-infused mice. In contrast to HGF, blockades of the renin-angiotensin system or Ang II infusion produced opposite effects on the PH-induce increases in hepatic transforming growth factor (TGF)-beta 1 mRNA and plasma TGF-beta 1 levels. These studies suggest that Ang II plays a role in the liver regeneration as a suppressor of hepatocyte proliferation via the AT(1) receptor-mediated control of growth factor production.


Immunohistochemical study of ras oncogene expression in endometrial and cervical human lesions.
The Y13 259 monoclonal antibody to the ras p21 protein was used in an immunohistochemical assay to study the levels of ras p21 in human uterine lesions as compared to normal tissue. Out of 73 hysterectomies obtained we have examined ras p21 expression in separately made sections from the endometrium, the cervix and leiomyomas found in the same specimens. A total of 155 tissue sections were finally evaluated and included: 55 endometrial mucosae (normal, hyperplastic and atrophic), 13 leiomyomas, 60 cervicitis (mild, moderate and severe with or without dysplasia), 3 in situ and 7 invasive carcinoma of the cervix, 12 invasive adenocarcinoma of the endometrium and 5 endometrial adenocarcinomas, which involved the cervical canal. Out of the 73 hysterectomy specimens 27 lesions were malignant and showed elevated expression of ras p21. The remaining 128 were normal or atrophic mucosae and benign or premalignant lesions, which were mostly negative. However, all cases of severe cervicitis and dysplasias and 6 out of the 12 hyperplastic endometrial lesions were found to be moderately or highly positive. Our results suggest that elevated expression of ras oncogenes may play an important role in the development of human uterine lesions.


The free energy of DNA supercoiling is enthalpy-determined.
The thermodynamics of superhelix formation was determined by combining superhelix density data with enthalpy values obtained from microcalorimetric measurements of the relaxation of supercoiled ColE1 amp plasmid DNA in the presence of topoisomerase I from Escherichia coli (omega protein). The thermodynamic quantities for superhelix formation at 37 degrees C in 10 mM Tris/2 mM MgCl2/1 mM EDTA pH 8, are: delta G = 921 kJ X (mol of plasmid)-1; delta H 2260 kJ X (mol of plasmid)-1; deltaS = 4.3 kJ X (mol of plasmid X K)-1. These data clearly demonstrate that the unfavorable Gibbs free energy associated with supercoiling of DNA results exclusively from the positive enthalpy involved in formation of superhelical turns. A positive overall entropy change accompanies superhelix formation, which overcompensates the expected decrease of configurational entropy. By neglecting contributions from bending, an estimate of the torsional rigidity C = 1.79 X 10(-19) erg X cm (1 erg = 0.1 microJ) of the supercoiled ColE1 amp plasmid DNA was made on the basis of the enthalpy value. This value is in excellent agreement with values of C derived from subnanosecond time-resolved fluorescence depolarization measurements for pBR322 DNA [Millar, D. P., Robbins, R. J. & Zewai, A.H. (1982) J. Chem. Phys. 76, 2080-2094]. The magnitude of C is larger than for linear DNAs, indicating that supercoiled DNA is more rigid than linear DNA.


Vitamin D Receptor polymorphisms and risk of enveloped virus infection: A meta-analysis.
Vitamin-D plays a role regulating the immune response against to viral infection. In this sense, vitamin-D deficiency may confer increased susceptibility to enveloped virus infection such as HIV, Hepatitis, Dengue and Respiratory Syncytial virus infection, among others. Vitamin D activity is mediated by its receptor (VDR), which acts as a transcription factor modulating the expression of genes triggering the response against viruses. To date, six major VDR polymorphisms (Cdx, A1012G, FokI, BsmI, ApaI and TaqI) have been studied in the context of viral infection susceptibility. Reported studies show controversial results probably due to statistical lack of power and population genetic differences. To do a systematic review of the published data and to perform a meta-analysis examining the role of six VDR polymorphisms on infection susceptibility to enveloped virus. From all markers and virus considered an association of FokI polymorphism with RSV infection emerges as significant. The worldwide distribution of risk T-allele reveals a lower prevalence in African populations that runs parallel with the relative lower incidence of RSV-associated severe ALRI in children <1 year described in African samples. The results disclose FokI polymorphism as a relevant variant capturing the association of VDR polymorphisms with viral infection.


[Age-associated morphological change in interventricular septum].
To investigate the morphological features of the interventricular septum (IVS) in the senile heart, we examined 123 normotensives (59 males and 64 females), ranging in age from 22 to 91 yrs using 2D echocardiography. End-diastolic IVS thickness was measured at the mid-portion (M) and at the thickest portion within 15 mm distal to the aorto-septal junction (basal portion, B) on left parasternal long-axis tomogram. The sigmoid shape of the basal portion was evaluated in terms of aorto-septal (AS) angle. M showed no correlation with age, whereas B increased significantly with age in both sexes (males, r = 0.42, p < 0.01; females, r = 0.51, p < 0.01). B/M ratio, therefore, also increased with age (males, r = 0.49, p < 0.01; females, r = 0.39, p < 0.01). The AS angle decreased with age in both sexes (males, r = -0.33, p < 0.01; females, r = -0.51, p < 0.01). There was a significant inverse correlation between B/M ratio and AS angle (males, r = -0.31, p < 0.05; females, r = -0.50, p < 0.01). We conclude that the B/M ratio is a novel index reflecting heterogenously distributed hypertrophy in the IVS associated with age.


The combined effects of the provision of feed and healthcare on nutrient utilization and growth performance of sheep during the early or late dry season.
An on-farm study was conducted to determine the combined effects of the provision of feed and healthcare on nutrient use and growth performance of sheep during the early or late dry season. A total of 36 smallholder sheep farmers with a flock size of ≤7 was randomly selected within each of the three administrative regions in Northern Ghana. The sheep grazed on a heterogeneous natural pasture and offered crop residues as basal diet (control) or were additionally provided with a concentrate feed plus orthodox healthcare to control diseases and pests (CH) in a completely randomized block design. The provision of orthodox healthcare included scheduled control of endo- and ecto-parasites and administration of broad-spectrum antibiotics. Data was analyzed for the fixed effects of CH, season, or CH × season using the mixed model procedure of Genstats®. The CH regimen had no effect (P = 0.098) on intake of natural pasture but pasture intake increased (P = 0.012) during the late dry season. Sheep on the CH regime had higher DM (P = 0.026) and N (P = 0.068) digestibility and improved ADG (P = 0.001) and feed conversion efficiency (P = 0.020) than those on the control. We hypothesize that improvements in growth performance of sheep on the CH regimen could be related to availability of nutrients for growth that will otherwise have been used for repair of damaged tissues caused by gastrointestinal parasites and ticks. Sheep on the CH regimen also had a higher concentration of fecal N during the late dry season when CP concentration was relatively higher than that in the early dry season (63.2 vs 60.9 g/day DM) when CP concentration of pasture was lower.


Characterization of Leiurus abdullahbayrami (Scorpiones: Buthidae) venom: peptide profile, cytotoxicity and antimicrobial activity.
Scorpion venoms are rich bioactive peptide libraries that offer promising molecules that may lead to the discovery and development of new drugs. Leiurus abdullahbayrami produces one of the most potent venoms among Turkish scorpions that provokes severe symptoms in envenomated victims. In the present study, the peptide profile of the venom was investigated by electrophoretic methods, size-exclusion and reversed-phase chromatography and mass spectroscopy. Cytotoxic and antimicrobial effects were evaluated on a breast cancer cell line (MCF-7) and various bacterial and fungal species. Proteins make up approximately half of the dry weight of L. abdullahbayrami crude venom. Microfluidic capillary electrophoresis indicated the presence of 6 to 7 kDa peptides and proved to be a highly practical peptidomics tool with better resolution when compared to conventional polyacrylamide gel electrophoresis. Mass spectroscopy analysis helped us to identify 45 unique peptide masses between 1 to 7 kDa with a bimodal mass distribution peaking between molecular weights of 1 to 2 kDa (29%) and 3 to 4 kDa (31%). L. abdullahbayrami crude venom had a proliferative effect on MCF-7 cells, which may be explained by the high concentration of polyamines as well as potassium and calcium ions in the arachnid venoms. Antimicrobial effect was stronger on gram-negative bacteria. This work represents the first peptidomic characterization of L. abdullahbayrami venom. Considering the molecular weight-function relationship of previously identified venom peptides, future bioactivity studies may lead to the discovery of novel potassium and chloride ion channel inhibitors as well as new antimicrobial peptides from L. abdullahbayrami venom.


Performance of the Front-of-Pack Nutrition Label Nutri-Score to Discriminate the Nutritional Quality of Foods Products: A Comparative Study across 8 European Countries.
Abstract: In Europe, discussions are currently ongoing to harmonize front-of-pack nutritional labelling, while some countries have adopted or are considering implementing the Nutri-Score. However, its adaptability to multiple nutritional contexts in Europe requires further investigation. This study aimed to evaluate the applicability of the Nutri-Score in various European countries, regarding its ability to discriminate the nutritional quality of foods and its consistency with national dietary recommendations. The European Food Information Resource (EUROFIR) nutritional composition databases from eight European countries (Finland, France, Norway, Poland, Portugal, Slovakia, Sweden, and Switzerland) were used. The distribution of foods across the Nutri-Score classes within food groups was assessed, as well as the discriminating performance of the label, and the adequacy of nutritional recommendations. The Nutri-Score demonstrated high discriminating ability for all food groups, with similar trends in the eight countries, and consistency with nutritional recommendations. For instance, fruit and vegetable products were mainly classified in the two healthiest Nutri-Score categories, while sugar and animal fat products were mainly classified in the two less healthy categories of the Nutri-Score. Our results support the fact that the Nutri-Score would be a relevant tool to discriminate the nutritional quality of products within and across relevant food groups in different European countries, with consistency with nutritional recommendations.


Replacement of a conserved tyrosine by tryptophan in Gal3p of Saccharomyces cerevisiae reduces constitutive activity: implications for signal transduction in the GAL regulon.
The ability of Saccharomyces cerevisiae to utilize galactose is regulated by the nucleo-cytoplasmic shuttling of a transcriptional repressor, the Gal80 protein. Gal80 interacts with the transcriptional activator Gal4 in the nucleus and inhibits its function, preventing induction of the GAL genes. In response to galactose, the relative amounts of Gal80 in the cytoplasm and the nucleus are modulated by the action of a signal transducer, Gal3. Although it has been speculated that Gal3 binds galactose, this has not been experimentally demonstrated. In this study, we show that replacement of a conserved tyrosine in Gal3 by tryptophan leads to a reduction of its constitutive activity in the absence of galactose. In addition, this mutant protein was fully functional in vivo only when high concentrations of galactose were present in the medium. When overexpressed, the mutant was found to activate the genes GAL1 and GAL7/10 differentially. The implications of these findings for the fine regulation of GAL genes, and its physiological significance, are discussed.


DNA enrichment by allele-specific hybridization (DEASH): a novel method for haplotyping and for detecting low-frequency base substitutional variants and recombinant DNA molecules.
Detecting rare sequence variants in genomic DNA is central to the analysis of de novo mutation and recombination events and the detection of rare pathological mutations in mixed cell populations. Current PCR techniques suffer from noise that limits detection to variants present at a frequency of at least 10(-4)-10(-5) per cell. We now describe an alternative approach that recovers genomic DNA molecules containing a known single-nucleotide variant by hybridization selection using a biotinylated allele-specific oligonucleotide, followed by hybrid capture on streptavidin-coated paramagnetic beads and subsequent analysis by PCR. This technique of DNA enrichment by allele-specific hybridization (DEASH) is fast, effective for all tested single-nucleotide polymorphisms (SNPs), and can recover large (>10 kb) single-stranded molecules. A single round of DEASH is effective in separating haplotypes from genomic DNA and can not only readily detect and validate DNA molecules containing a single base change at a frequency of 10(-5) per cell, but can also place these changes within the context of an extended haplotype. This technique offers a new approach to the analysis of mutation and recombination, and has the potential to detect very rare de novo base substitutions.


Co-culture with normal and senescent AC16 cardiomyocytes modulates fibrotic response in primary human ventricular fibroblasts.
Transwell co-culture with human AC16 cardiomyocyte-like cells modifies the response of primary human ventricular fibroblasts to TGF-β stimulation. Fibrotic response markers including collagen I (COL1A1) and ɑ-smooth muscle actin (ACTA2) are amplified in the presence of AC16 cells, whereas others including periostin (POSTN) and fibronectin (FN1) are suppressed. Similar modulation is observed when the ventricular fibroblasts are co-cultured with AC16 cells under baseline and induced senescence conditions. Given that the response to TGF-β stimulation is commonly measured to study fibrotic signaling and drug treatments in vitro, the results here suggest that the effect of cellular crosstalk should be more broadly considered.


The epidemiology of multiple-clone Plasmodium falciparum infections in Gambian patients.
The occurrence of multiple-clone Plasmodium falciparum haploid blood-stage infections is a pre-requisite for cross-fertilization and genetic exchange at the diploid stage in the mosquito. Using monoclonal antibodies against 3 polymorphic blood-stage antigens, a method of two-colour differential immunofluorescence allowed the resolution of between 1 and 4 clones/isolate. A mean of 2 P. falciparum clones was detected in the blood of malaria patients in The Gambia. The mean number of clones/patient showed no correlation with age, parasitaemia, or disease severity. There was a slight difference in mean number between sample periods, probably reflecting temporal differences in transmission intensity. A statistical analysis of 2-locus genetic diversity of clones within isolates concludes that not all multiple-clone infections result from superinfection, but that some are due to single multiple-clone inoculations.


Effect of short exposures to spinetoram against three stored-product beetle species.
Laboratory bioassays were carried out to evaluate the effectiveness of two formulations of spinetoram, water dispersible granules (WG), and suspension concentrate (SC-NC), against three major stored-grain beetle species, the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae); the rice weevil, Sitophilus oryzae (L.) (Coleoptera: Curculionidae); and the confused flour beetle, Tribolium confusum Jacquelin du Val (Coleoptera: Tenebrionidae). Adults of the above species were exposed on wheat treated with spinetoram at 1 ppm (1 mg/kg of wheat) for 0, 2, 4, 6, 8, 16, 40, and 72 h. After this interval, mortality was recorded (immediate mortality) and the surviving individuals were transferred in untreated wheat, where mortality was recorded again 7 d later (delayed mortality). Then, all adults were removed, and the number of progeny production in the untreated substrate was measured 65 d later. From the species tested, R. dominica was by far the most susceptible, given that immediate and delayed mortality for the 72-h exposure interval reached 44 and 97%, respectively. At the same time, progeny production was low, in most of the exposure intervals tested. In contrast, for S. oryzae, delayed mortality was negligible, with the exception of 72 h at the SC-NC formulation. However, in most of the cases examined, progeny production for S. oryzae was high. Finally, adult mortality for T. confusum was extremely low, regardless of the exposure interval and the type of the formulation. Nevertheless, offspring emergence of this species was low. By combining the results of the current study and the data that are available from the literature for short exposures to spinosad, we can conclude that the two ingredients were equally effective against these three stored-grain beetle species.


The interplay between metabolic remodeling and immune regulation in glioblastoma.
The fields of tumor metabolism and immune oncology have both independently received considerable attention over the last several years. The majority of research in tumor metabolism has largely focused on the Warburg effect and its resulting biologic consequences, including energy and macromolecule production. However, recent investigations have identified elegant, multifaceted strategies by which alterations in tumor metabolism can also contribute to a potent tolerogenic immune environment. One of the most notable is increased tryptophan metabolism through activation of indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). However, this pathway represents one of numerous metabolic pathways that may modulate the immune system. For example, metabolites associated with aerobic glycolysis, adenosine, arginine, and prostaglandin metabolism have all been implicated in cancer-mediated immune tolerance and represent attractive therapeutic targets. In this review, we will provide an overview of the emerging interface between these 2 timely areas of cancer research and provide an overview of strategies currently being tested to target these next-generation metabolic immune checkpoints.


[Cost-effectiveness of an organized breast cancer screening program in Southern Brazil].
The aim of this study was to evaluate the cost-effectiveness of an organized breast cancer mammographic screening program implemented in Porto Alegre (Núcleo Mama Porto Alegre - NMPOA), Rio Grande do Sul State, Brazil. A Markov model was constructed to estimate the incremental cost-effectiveness ratio of NMPOA compared to current BC diagnosis and care in the Brazilian public health system, in a hypothetical cohort of women aged 40-69 years at risk of developing breast cancer. Model parameters were collected from NMPOA and the national literature. In the NMPOA strategy, effectiveness was modeled taking into account the actual observed screening adherence. Effectiveness was measured in quality-adjusted life years (QALYs). Incremental cost-effectiveness ratio in the base case was R$ 13,426 per QALY. This result was not sensitive to variation in the main model parameters in sensitivity analyses. Considering the threshold usually suggested as highly attractive in Brazil, breast cancer screening as performed in NMPOA is cost-effective in cities with high incidence of breast cancer.