Visual Outcomes After Endoscopic Endonasal Resection of Orbital Lesions.
The endoscopic endonasal approach (EEA) has been increasing in popularity as an alternative to traditional transcranial and transorbital approaches in the treatment of orbital pathological entities. The purpose of the present study was to examine the outcomes of patients who had undergone EEA resection of orbital lesions at our center. We performed a retrospective medical record review of patients who had undergone the EEA for resection of orbital lesions and orbital apex decompression from January 1, 2006 to December 1, 2019. For all the patients, the demographic data, presenting symptoms, symptom duration, imaging data, operative details, and postoperative outcomes were collected and reviewed. Nine patients underwent endoscopic endonasal resection of orbital lesions and orbital apex decompression at our center, including 6 male patients and 3 female patients. The mean age was 49.4 years, and the mean follow-up period was 3.8 years (range, 1-13.5 years). The orbital pathological lesions that were treated included nasopharyngeal carcinoma, hemangioma, fibrous dysplasia, IgG4 pseudotumor, inverted papilloma, angioleiomyoma, adenocarcinoma, and neuroendocrine paraganglioma metastasis. All the patients presented with exophthalmos of the affected orbit. Of the 9 patients, 5 presented with decreased visual acuity on examination. Postoperatively, 1 of these 5 patients had improved to baseline visual acuity, 3 had stable vision, and 1 had brief improvement before experiencing progressive visual decline 1 month postoperatively. Two patients presented with diplopia, and both improved postoperatively. Three patients experienced new, transient, and self-limiting postoperative diplopia. For patients with orbital lesions causing compressive optic neuropathy, the endoscopic endonasal approach can be used as an alternative strategy in appropriately selected patients.


Behavioral science, engineering, and poetry revisited.
Forty years ago, Lehrman (1971) identified 2 orientations to the study of animal behavior. The natural history orientation conducted field and lab research designed to reveal how animals cope with the circumstances of their natural environment. Such research reveals the diversity among different types of animals and differences between the world of animals and the world of humans (i.e., "poetry"). In contrast, the anthropocentric orientation studies animals either to generate animal-derived general laws applicable to humans or to provide experimental information that, for ethical and practical reasons, cannot be acquired from human research. The primary motivation for the anthropocentric orientation is to provide workable models for investigating specifically human problems (i.e., "engineering"). Evidence is presented from the study of bird song that demonstrates the contribution that the "poetic" approach can make to anthropocentric ("engineering") concerns.


Immunoblastic lymphoma: a clinicopathologic study with emphasis on the cases intervening during or following other disorders.
Fifty-eight patients with immunoblastic lymphoma (IBL) were the object of this study. Fifteen of them (26%) developed IBL during or after other diseases, either immunologic or neoplastic, including angio-immunoblastic lymphadenopathy, autoimmune disorders, chronic lymphocytic leukemia, Waldenström's disease, lymphoplasmacytoid lymphoma and Hodgkin's disease (subsequent IBL). The comparison between de novo and subsequent IBL revealed a significantly higher incidence of bone marrow involvement and bulky abdominal disease in the latter group, with a lower response rate to chemotherapy. The favorable primary extranodal disease of Waldeyer's ring exclusively belonged to de novo IBL, whereas the frequency of immunoglobulin abnormalities was higher in the subsequent IBL group (67%). The stage of disease, systemic symptoms at diagnosis and response to therapy were predictive of survival. The overall complete remission (CR) rate in the whole series was 37% and the median overall survival 14 months. Complete remitters have a median survival in excess of 60 months; all relapses occurred within the first 12 months of CR. No CNS relapse terminated the CR, and CNS prophylaxis seems unnecessary in IBL. The analysis of subsequent IBL may provide information on the pathogenesis of non-Hodgkin's lymphomas; the still poor prognosis of IBL deserves new therapeutic attempts to improve on the standard regimens.


Auxin: a regulator of cold stress response.
The growth hormone auxin regulates essentially all aspects of plant developmental processes under optimum condition. However, as a sessile organism, plants encounter both optimal and non-optimal conditions during their life cycle. Various biotic and abiotic stresses affect the growth and development of plants. Although several phytohormones, such as salicylic acid, jasmonate and ethylene, have been shown to play central roles in regulating the plant development under biotic stresses, the knowledge of the role of hormones, particularly auxin, in abiotic stresses is limiting. Among the abiotic stresses, cold stress is one of the major stress in limiting the plant development and crop productivity. This review focuses on the role of auxin in developmental regulation of plants under cold stress. The emerging trend from the recent experiments suggest that cold stress induced change in the plant growth and development is tightly linked to the intracellular auxin gradient, which is regulated by the polar deployment and intracellular trafficking of auxin carriers.


Assessment of the relationship between bacteriological quality of dug-wells, hygiene behaviour and well characteristics in two cholera endemic localities in Douala, Cameroon.
Access to potable water is grossly inadequate in Douala-Cameroon. The situation is worse in slum areas, compelling inhabitants to obtain water from sources of doubtful quality. This has contributed to frequent outbreaks of water-borne diseases particularly cholera, which results in severe morbidity and mortality. Shallow wells are a major source of water in these areas. We analyzed the influence of some factors on the bacteriological quality of well water in Bepanda and New Bell, cholera endemic localities in Douala to generate data that would serve as basis for strengthening of water and health policies. Questionnaires were administered to inhabitants of study sites to appraise their hygiene and sanitation practices, and level of awareness of waterborne diseases. The bacteriological quality of water was determined by investigating bacterial indicators of water quality. Relationship between well characteristics and bacteriological quality of water was determined using χ² test. The Kendall tau_b nonparametric correlation was used to measure the strength of association between well characteristics and bacteriological parameters. Statistics were discussed at 95% confidence level. Antibiotic susceptibility of isolates was investigated by the Kirby-Bauer and broth dilution techniques. Multidrug resistant species were tested for extended β-lactamase production potential. Inhabitants demonstrated adequate knowledge of waterborne diseases but employed inappropriate method (table salt) for well disinfection. Well construction and location violated guidelines. Indicator bacterial counts greatly exceeded the WHO guidelines. Variation in bacteriologic parameters between sites was not significant (P > 0.05) since well characteristics and hygiene and sanitary practices were similar. Differences in bacteriologic quality with respect to state of well, and presence of molded casing and lid, and height of casing were not significant (P > 0.05). Well distance from sanitary structure negatively correlated with bacteriological characteristics indicating it could be a major contributory factor to poor water quality. Bacteria isolated were predominantly enteric organisms. Ciprofloxacin was the most active agent. Extended β-lactamase producers were detected among Salmonella species, Citrobacter fruendii and E. coli. Poor well location, construction, and hygiene and sanitary practices were among the factors affecting water quality. There is an urgent need for education of inhabitants on effective water disinfection strategies and for regular monitoring of wells.


[Surgical endoscopy in polyps and adenomas of the colon].
Endoscopic polypectomy being a standard procedure for "normal" colorectal polyps, big and complicated polyps and adenomas, however, are mostly subject to surgical operations. The analysis of 3300 polypectomies performed in the own institution with up to 36% difficult polyps shows, that using new techniques for submucosal injection (SIT) and innovative rf-surgical technologies (FC) even these difficult polyps can be removed with very low complication rates. Technical and oncological aspects however, have to be respected thoroughly.


Eye white percentage as a predictor of temperament in beef cattle.
Accurately evaluating and selecting for calm temperament in beef cattle is important for economic and animal welfare reasons. Previous studies have shown that eye white (EW) can be a predictor of a multitude of emotions across different situations, but there is little research on the relationship between EW and temperament. The objective of this experiment was to assess the accuracy and reliability of using the percentage of exposed EW as a predictor of temperament in beef cattle. Forty-eight heifers (group 1), 39 bulls (group 2), and 60 steers (group 3) were video-recorded while in a squeeze chute, and 2 still digital images from each animal were selected for EW determination. Chute temperament scores were assigned: 1 (calm) to 5 (agitated). Flight speeds were measured blindly and independently during a subsequent test in which the amount of time it took a solitary animal to pass a handler and travel a specified distance was recorded. The EW area in each image was measured using Sigmascan Pro 5 and was expressed as the percentage of exposed eye area. Each image was analyzed twice to determine tracing repeatability. Pearson correlation coefficients were calculated among 2 images of the same animal, as well as among duplicate readings of the same image to determine animal and tracing repeatabilities. The mean percentages of EW were 30.14 +/- 14.37, 31.43 +/- 14.77, and 28.57 +/- 12.38, and the average percentage accuracy for duplicate image EW measures was 96, 96, and 93 (P < 0.0001) for groups 1, 2, and 3, respectively. The Pearson correlation coefficients for EW percentage and chute temperament scores were 0.674 (P < 0.0001), 0.95 (P < 0.0001), and 0.696 (P < 0.0001), whereas the correlations between EW and flight speeds were 0.415 (P < 0.0001), 0.333 (P < 0.05), and 0.294 (P < 0.01) for groups 1, 2, and 3, respectively. Results from this study indicate that percentage EW in cattle could be used as a quantitative tool with minimal equipment to assess temperament in beef cattle, providing an objective method for temperament selection.


Optimization of silver nanowire networks for polymer light emitting diode electrodes.
Silver nanowire (Ag NW) networks are promising candidates for replacement of indium tin oxide (ITO). However, transparent conductors based on Ag NW networks often suffer from 'haziness' resulting from surface roughness. Thus, in addition to achieving suitable transparency and conductivity, surface roughness must be minimized if realistic implementation of Ag NW networks as transparent conductors is to be realized. In this work, we have reduced the surface roughness of Ag NW networks to below 5 nm as compared to 54 nm for as-deposited Ag NWs through optimization of the low temperature annealing treatment and planarization by poly(3,4 ethylenedioxythiophene)-poly(styrenesulfanate). Using this method, we have been able to produce Ag NW networks with transmittances and sheet resistances of 87% and 11Ω/sq, respectively. These are some of the best values reported for non-oxide-based transparent conductors. Incorporation of these smooth Ag networks into polymer light emitting diodes fabricated in our laboratory yields device characteristics that are comparable to or better than those with commercially available ITO.


Promiscuous signaling by a regulatory system unique to the pandemic PMEN1 pneumococcal lineage.
Streptococcus pneumoniae (pneumococcus) is a leading cause of death and disease in children and elderly. Genetic variability among isolates from this species is high. These differences, often the product of gene loss or gene acquisition via horizontal gene transfer, can endow strains with new molecular pathways, diverse phenotypes, and ecological advantages. PMEN1 is a widespread and multidrug-resistant pneumococcal lineage. Using comparative genomics we have determined that a regulator-peptide signal transduction system, TprA2/PhrA2, was acquired by a PMEN1 ancestor and is encoded by the vast majority of strains in this lineage. We show that TprA2 is a negative regulator of a PMEN1-specific gene encoding a lanthionine-containing peptide (lcpA). The activity of TprA2 is modulated by its cognate peptide, PhrA2. Expression of phrA2 is density-dependent and its C-terminus relieves TprA2-mediated inhibition leading to expression of lcpA. In the pneumococcal mouse model with intranasal inoculation, TprA2 had no effect on nasopharyngeal colonization but was associated with decreased lung disease via its control of lcpA levels. Furthermore, the TprA2/PhrA2 system has integrated into the pneumococcal regulatory circuitry, as PhrA2 activates TprA/PhrA, a second regulator-peptide signal transduction system widespread among pneumococci. Extracellular PhrA2 can release TprA-mediated inhibition, activating expression of TprA-repressed genes in both PMEN1 cells as well as another pneumococcal lineage. Acquisition of TprA2/PhrA2 has provided PMEN1 isolates with a mechanism to promote commensalism over dissemination and control inter-strain gene regulation.


Combination therapy with renin-angiotensin system inhibitors and the calcium channel blocker azelnidipine decreases plasma inflammatory markers and urinary oxidative stress markers in patients with diabetic nephropathy.
A calcium channel blocker (CCB), azelnidipine (AZ), is reported to inhibit oxidative stresses, particularly when administered under blockade of the renin-angiotensin system (RAS). The purpose of this study was to investigate whether AZ inhibits oxidative stresses more potently than other CCBs under blockade of RAS and exerts renoprotection in type 2 diabetic nephropathy. Subjects were hypertensive type 2 diabetics with nephropathy, taking RAS inhibitors. The patients were randomly assigned to two groups, an AZ group (n=21, 16 mg/d) and a nifedipine-CR (NF) group (n=17, 40 mg/d). The plasma levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), adiponectin and tumor necrosis factor-alpha (TNF(alpha)), the urinary excretion of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) and 8-hydroxydeoxyguanosine (8-OHdG), and the urinary albumin-to-creatinine ratios (ACR) were determined before and after 16-week treatment. Neither metabolic parameters nor blood pressure levels differed between the two groups not only at baseline but also after the treatment. However, significant decreases in MCP-1, IL-6, hsCRP, TNF(alpha), 8-epi-PGF(2alpha), 8-OHdG and ACR levels, and a significant increase in the plasma adiponectin level were detected in the AZ group, but not in the NF group. The % change in the urinary oxidative stress markers correlated with that in ACR. Our results indicate that, in hypertensive patients with diabetic nephropathy, a combination therapy of RAS inhibitors and AZ is an effective therapeutic modality for decreasing not only blood pressure but also inflammations and oxidative stresses.


Curcumin, a nutritional supplement with antineoplastic activity, enhances leiomyoma cell apoptosis and decreases fibronectin expression.
To determine if curcumin has an antiproliferative effect on leiomyoma cells via apoptosis induction and whether curcumin impacts extracellular matrix (ECM) production by assessing the fibronectin expression in leiomyoma cells treated with curcumin. Tissue culture study of immortalized human leiomyoma and patient-matched myometrial cells treated with curcumin. University hospital. Immortalized leiomyoma and myometrial cells from patients with symptomatic leiomyomata. Tissue culture, followed by proliferation studies, RNA, and protein analysis. Cell proliferation, alteration in apoptotic signaling pathways. Curcumin demonstrated an antiproliferative effect on leiomyoma cell lines (IC50 = 20 muM). Importantly, no statistically significant inhibition of growth was observed when patient-matched myometrial cells were exposed to equivalent concentrations of curcumin. Curcumin stimulated caspase-3 and caspase-9 expression while inhibiting extracellular signal-regulated kinase 1 (ERK 1), ERK 2, and nuclear factor kappa B (NF-kappaB), suggesting regulation of leiomyocyte apoptosis. Finally, curcumin inhibited expression of fibronectin in leiomyoma cells. Our findings demonstrate that curcumin inhibited uterine leiomyoma cell proliferation via regulation of the apoptotic pathway, and inhibited production of the ECM component fibronectin. Curcumin provides a novel direction for leiomyoma therapies.


Associations between prenatal and infancy weight gain and BMI, fat mass, and fat distribution in young adulthood: a prospective cohort study in males and females born very preterm.
Increasing evidence indicates that adult body composition is associated with prenatal and infancy weight gain, but the relative importance of different time periods has not been elucidated. The objective was to study the association between prenatal, early postnatal, and late infancy weight gain and body mass index (BMI), fat mass, and fat distribution in young adulthood. We included 403 men and women aged 19 y from a Dutch national prospective follow-up study who were born at <32 wk of gestation. BMI, waist circumference, and waist-to-hip ratio SD scores and subscapular-to-triceps ratio, percentage body fat, fat mass, and fat-free mass at age 19 y were studied in relation to birth weight SD scores, weight gain from preterm birth until 3 mo postterm (early postnatal weight gain), and weight gain from 3 mo until 1 y postterm (late infancy weight gain). Birth weight SD scores were positively associated with weight, height, BMI SD scores, and fat-free mass at age 19 y but not with fat mass, percentage body fat, or fat distribution. Early postnatal and late infancy weight gain were positively associated with adult height, weight, BMI, waist circumference SD scores, fat mass, fat-free mass, and percentage body fat but not with waist-to-hip ratio SD scores or subscapular-to-triceps ratio. In infants born very preterm, weight gain before 32 wk of gestation is positively associated with adult body size but not with body composition and fat distribution. More early postnatal and, to a lesser extent, late infancy weight gain are associated with higher BMI SD scores and percentage body fat and more abdominal fat at age 19 y.


Attitudes of older people with mild dementia and mild cognitive impairment and their relatives about falls risk and prevention: A qualitative study.
To explore the perceptions of older people with mild dementia and mild cognitive impairment, and their family carers, about falling, falls risk and the acceptability of falls prevention interventions. Qualitative study involving thematic analysis of semi-structured interviews with patient and relative dyads. 20 patient/ relative dyads recruited from Memory Assessment Services and Falls Prevention Services in the United Kingdom. The findings are presented under four key themes: attitudes to falls, attitudes to falls prevention interventions, barriers and facilitators, and the role of relatives. Participants' attitudes to falls interventions were varied and sometimes conflicting. Some worried about falls, but many resisted identifying themselves as potential 'fallers', even despite having fallen, and rejected the idea of needing the help that structured interventions signify. Participants preferred to focus on coping in the present rather than anticipating, and preparing for, an uncertain future. Falls prevention interventions were acknowledged to be valuable in principle and if required in the future but often felt to be not necessary or appropriate at present. This study of how persons with cognitive impairment, and their relatives, view falls risk and prevention mirror findings relating to the wider population of older persons without dementia. Participants did not generally see falls prevention interventions as currently relevant to themselves. The challenge for clinicians is how to present interventions with understanding and respect for the older person's identity. They must identify and address goals that patients and relatives value. Simplistic or paternalistic approaches will likely fail. Individualised interventions which focus on maintaining independence and preserving quality of life are more likely to be acceptable by supporting a positive self-image for patients and their relatives.


Elucidation of cellular metabolism via metabolomics and stable-isotope assisted metabolomics.
Metabolomics and metabolic flux analysis (MFA) are powerful tools in the arsenal of methodologies of systems biology. Currently, metabolomics techniques are applied routinely for biomarker determination. However, standard metabolomics techniques only provide static information about absolute or relative metabolite amounts. The application of stable-isotope tracers has opened up a new dimension to metabolomics by providing dynamic information of intracellular fluxes and, by extension, enzyme activities. In the first part of the manuscript we review experimental and computational technologies applicable for metabolomics analyses. In the second part we present current technologies based on the use of stable isotopes and their applications to the analysis of cellular metabolism. Beginning with the determination of mass isotopomer distributions (MIDs), we review technologies for metabolic flux analysis (MFA) and conclude with the presentation of a new methodology for the non-targeted analysis of stable-isotope labeled metabolomics data.


IL-6 and leukemia-inhibitory factor are involved in the generation of tumor-associated macrophage: regulation by IFN-γ.
Tumor-associated macrophages (TAMs), the most abundant immunosuppressive myeloid cells in the tumor microenvironment, exhibit an IL-10(high)IL-12(low) profile called M2, opposite to the immunostimulatory M1. We reported that ovarian cancer ascites switched monocyte differentiation into TAM-like cells that exhibit most phenotypic and functional characteristics of TAMs, suggesting that soluble mediators are involved in the differentiation of monocytes into TAM-like cells. We observed that leukemia-inhibitory factor and IL-6, present at high concentrations in ovarian cancer ascites, skew monocyte differentiation into TAM-like cells by increasing macrophage colony-stimulating factor consumption. Moreover, we observed that IFN-γ switches established TAMs into immunostimulatory M1 cells and skews monocyte differentiation from TAM-like cells to M1s. In addition to revealing a new tumor-escape mechanism associated with TAM generation via leukemia-inhibitory factor and IL-6, these findings offer novel therapeutic perspectives to subvert TAM-induced immunosuppression and to improve antitumor immunotherapy efficacy.


Charge Transport Across Au-P3HT-Graphene van der Waals Vertical Heterostructures.
Hybrid van der Waals heterostructures based on 2D materials and/or organic thin films are being evaluated as potential functional devices for a variety of applications. In this context, the graphene/organic semiconductor (Gr/OSC) heterostructure could represent the core element to build future vertical organic transistors based on two back-to-back Gr/OSC diodes sharing a common graphene sheet, which functions as the base electrode. However, the assessment of the Gr/OSC potential still requires a deeper understanding of the charge carrier transport across the interface as well as the development of wafer-scale fabrication methods. This work investigates the charge injection and transport across Au/OSC/Gr vertical heterostructures, focusing on poly(3-hexylthiophen-2,5-diyl) as the OSC, where the PMMA-free graphene layer functions as the top electrode. The structures are fabricated using a combination of processes widely exploited in semiconductor manufacturing and therefore are suited for industrial upscaling. Temperature-dependent current-voltage measurements and impedance spectroscopy show that the charge transport across both device interfaces is injection-limited by thermionic emission at high bias, while it is space charge limited at low bias, and that the P3HT can be assumed fully depleted in the high bias regime. From the space charge limited model, the out-of-plane charge carrier mobility in P3HT is found to be equal to μ ≈ 2.8 × 10-4 cm2 V-1 s-1, similar to the in-plane mobility reported in previous works, while the charge carrier density is N0 ≈ 1.16 × 1015 cm-3, also in agreement with previously reported values. From the thermionic emission model, the energy barriers at the Gr/P3HT and Au/P3HT interfaces result in 0.30 eV and 0.25 eV, respectively. Based on the measured barriers heights, the energy band diagram of the vertical heterostructure is proposed under the hypothesis that P3HT is fully depleted.


Should annuloplasty prosthesis be selected dependent on the location of prolapse in mitral valve repair for type II dysfunction?
This study explored the influence of prosthesis selection on long-term outcomes in patients who underwent mitral valve repair for mitral insufficiency (MI) due to type II dysfunction. We retrospectively reviewed 452 patients with MI who underwent mitral valve repair for type II dysfunction between 2001 and 2014. Of these, 167 patients (37%) presented with anterior leaflet prolapse (anterior group) and 285 (63%) presented with posterior prolapse (posterior group). Full rings were applied in 95 patients (57%) in the anterior group and in 54 patients (19%) in the posterior group, and partial bands were applied in all others. We compared long-term outcome and change of MI severity over time between patients with partial-band and full-ring repair in the anterior and in the posterior groups using a mixed-effect model with repeated measures and propensity score-matched analysis. Ten-year survival of the cohort was 90.5%. Echocardiography revealed MI ≥ 3 at follow-up in 58 patients (12.8%). Twenty-one patients (4.6%) required reoperation; freedom from reoperation was 92.1% at 10 years. The MI severity over time in patients in the anterior group was higher than that in patients in the posterior group (P < .0001). Moreover, MI severity over time in patients with the partial band was higher than patients with the full ring in the anterior group (P = .0176). Propensity score-matched analysis in the anterior group, but not in the posterior group, revealed a significantly higher MI severity in patients with the partial band than those with the full ring over the study period (P = .04). Full-ring annuloplasty is indicated in the setting of anterior prolapse to prevent recurrent MI, whereas prosthesis type is not a determinant of recurrent MI in the setting of posterior prolapse.


Post-discharge nutrition of the very low-birthweight infant: interim results of the multicentric GAMMA study.
This report presents the interim results up to 12 mo corrected age (c.a.) of a multicentric, prospective, controlled study on very low-birthweight infants, randomized at 40 wk post-conception in two different groups of formula feeding: 80 Kcal/dL (group A) vs 70 Kcal/dL (group B) up to 55 wk of postconceptional age. Subsequently, all the babies were fed with a follow-on formula, with the introduction of solid foods at 6 mo c.a. Weight, length, head circumference and neurological conditions with psychomotor development (evaluated by the Griffiths' Developmental Scale) were measured at regular intervals and all of these parameters were satisfactory in both groups. For growth, in group A there was a greater increase in weight in boys at 55 wk and at 6 mo c.a., and small for gestational age (SGA) babies had a greater increase in length at 1 y of age, while head circumference caught up on growth from week 40 to week 55. Measured by the Griffiths' Developmental Scale, the SGA group fed 80 Kcal/dL had a better score at 6 mo; similarly boys fed 80 Kcal/dL had a better score at 6 and at 9 mo. Nutrition of very low birthweight infants post-discharge could have an influence on physical growth and on neurodevelopmental outcome. This interim report needs to be confirmed at the end of the study.


Mastering uncertainty: A predictive processing account of enjoying uncertain success in video game play.
Why do we seek out and enjoy uncertain success in playing games? Game designers and researchers suggest that games whose challenges match player skills afford engaging experiences of achievement, competence, or effectance-of doing well. Yet, current models struggle to explain why such balanced challenges best afford these experiences and do not straightforwardly account for the appeal of high- and low-challenge game genres like Idle and Soulslike games. In this article, we show that Predictive Processing (PP) provides a coherent formal cognitive framework which can explain the fun in tackling game challenges with uncertain success as the dynamic process of reducing uncertainty surprisingly efficiently. In gameplay as elsewhere, people enjoy doing better than expected, which can track learning progress. In different forms, balanced, Idle, and Soulslike games alike afford regular accelerations of uncertainty reduction. We argue that this model also aligns with a popular practitioner model, Raph Koster's Theory of Fun for Game Design, and can unify currently differentially modelled gameplay motives around competence and curiosity.


Segmentation of zebrafish embryonic images using a geometric atlas deformation.
Transgenic zebrafish expressing fluorescent proteins in specific tissues or organs are promising models for studies of normal developmental processes, or perturbations of these. However, for widespread use, reliable quantification of the observed effects is necessary. Therefore, accurate and automatic analysis of images obtained by fluorescent microscopy and depicting zebrafish embryos becomes crucial. In this paper, a segmentation approach for such images is proposed. The segmentation is achieved by fitting a species-specific 2D atlas to the zebrafish data depicted in the images. Experiments performed in a set of 50 images have provided promising results.


Switching curve controller for FES-assisted standing up and sitting down.
A low-level, closed-loop controller for FES-assisted standing up and sitting down is described. If, for able-bodied individuals, when standing up and sitting down, the knee angular velocity is plotted against knee angle, consistent phase-plane trajectories are produced. The bang-bang controller uses a model of this trajectory as a switching curve. The design rationale for the controller was the desire to avoid injuries that might occur if knee-locking on standing up and seat-contact on sitting down are not adequately controlled. This switching curve controller (SCC) was incorporated within a hierarchical, finite state control scheme, with electrical stimulation applied bilaterally to the knee extensors. The SCC was tested in a pilot study on a female volunteer with paraplegia (T5/6 ASIA A) and evaluated against an unramped, open-loop controller (OLC). The vertical hand forces and knee angles were measured. The subject was able to achieve standing up and sitting down safely using both controllers. For standing up, the SCC was not found to offer any quantifiable advantages over the OLC and was found to increase the hand force by 8.4%. In contrast, for sitting down the SCC was found to reduce the knee angular velocities as the subject approached the seat by 27%, demonstrating a safer, softer landing.


Investigation of the polarization optics of the living human cornea and lens with purkinje images.
We present what to our knowledge is a new method for assessing the polarization optics of the cornea and lens, by examining the state of polarization of the first, second, and fourth Purkinje images. When linearly polarized light is incident on the cornea at 70 degrees to the line of gaze along the horizontal meridian, and then traverses the cornea, or the cornea and the lens, the emergent light is elliptically polarized. The degree of ellipticity varies widely between subjects. The results indicate that both the cornea and the lens may be optically active and to our knowledge are the first to suggest that the cornea may exhibit circular birefringence.


Differential effects of glucocorticoids on bone resorption in neonatal mouse calvariae stimulated by peptide and steroid-like hormones.
Differential effects on in vitro bone resorption were observed when the glucocorticoids, hydrocortisone and dexamethasone, were added to neonatal mouse calvariae treated with either parathyroid hormone (PTH), 1,25(OH)2-vitamin D3, all trans-retinoic acid (t-RA), or prostaglandin E2 (PGE2). Bone resorption was assessed by analyzing either the release of 45Ca from [45Ca]CaCl2 prelabeled calvarial bones or the release of 3H from [3H]proline prelabeled calvariae. At PGE2 concentrations of 3 x 10(-8) and 3 x 10(-7) mol/l, co-treatment with either 10(-6) mol/l dexamethasone or 10(-6) mol/l hydrocortisone caused additive 45Ca release from neonatal mouse calvariae. In contrast, synergistic release from mouse calvarial bones of both 45Ca and 3H was found after either 10(-6) mol/l hydrocortisone or 10(-6) mol/l dexamethasone was combined with 3 x 10(-11) mol/l PTH treatment for 120 h. Dose-response studies indicated that the synergistic stimulation of 45Ca release from neonatal mouse calvariae by glucocorticoids and PTH could be elicited at glucocorticoid concentrations of 10(-8) to 10(-6) mol/l and at PTH concentrations of 10(-11) to 10(-9) mol/l. Progesterone and RU 38486 (a derivative of 19-nortestosterone with antiglucocorticoid activity) blocked the synergism noted with glucocorticoid and PTH co-treatment, suggesting that interaction between the steroids and PTH was dependent on glucocorticoid receptor interaction. Addition of either 10(-6) mol/l hydrocortisone or 10(-6) mol/l dexamethasone to neonatal mouse calvariae treated with 1,25(OH)2-vitamin D3 (10(-11) and 10(-10) mol/l) also resulted in synergistic stimulation of 45Ca release. In contrast to these observations, the stimulatory effect of t-RA (10(-8) mol/l) on 45Ca release from calvarial bones was abolished in the presence of 10(-6) mol/l dexamethasone. These results suggest that an important role of glucocorticoids may be to synergistically potentiate bone resorption stimulated by PTH and 1,25(OH)2-vitamin D3, but indicate an opposing interaction between the glucocorticoids and bone resorptive retinoids.


Sol-gel SELEX circumventing chemical conjugation of low molecular weight metabolites discovers aptamers selective to xanthine.
Sensitive detection of the metabolites indicative of a particular disease contributes to improved therapy outcomes. Developing binding reagents for detection of low molecular weight metabolites is hampered by the difficulty with immobilization of targets through appropriate covalent chemical linkage while ensuring that selected reagents retain specificity to unmodified metabolites. To circumvent chemical modification of targets, we employed sol-gel droplets deposited onto a porous silicon chip to entrap a purine metabolite, xanthine, which was found at lower levels in urine samples from patients with non-Hodgkin lymphoma. By sol-gel SELEX (systematic evolution of ligands by exponential enrichment) against xanthine, specific aptamers (KD ∼ 10 μM) with sensitivity of detection at as low as 1 μM were isolated, which bound to other purine metabolites at more than 100-fold lower affinity. In contrast, we failed to isolate xanthine-specific aptamers when SELEX was performed against xanthine covalently linked to polymer resin. This study demonstrates that the sol-gel platform for entrapping low molecular weight metabolites without chemical modifications can be utilized for SELEX to discover aptamers against clinical metabolite markers for diagnosis application.


Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen.
Collagen degradation by phagocytosis is essential for physiological collagen turnover and connective tissue homeostasis. The rate limiting step of phagocytosis is the binding of specific adhesion receptors, which include the integrins and discoidin domain receptors (DDR), to fibrillar collagen. While previous data suggest that these two receptors interact, the functional nature of these interactions is not defined. In mouse and human fibroblasts we examined the effects of DDR1 knockdown and over-expression on β1 integrin subunit function. DDR1 expression levels were positively associated with enhanced contraction of floating and attached collagen gels, increased collagen binding and increased collagen remodeling. In DDR1 over-expressing cells compared with control cells, there were increased numbers, area and length of focal adhesions immunostained for talin, paxillin, vinculin and activated β1 integrin. After treatment with the integrin-cleaving protease jararhagin, in comparison to controls, DDR1 over-expressing cells exhibited increased β1 integrin cleavage at the cell membrane, indicating that DDR1 over-expression affected the access and susceptibility of cell-surface β1 integrin to the protease. DDR1 over-expression was associated with increased glycosylation of the β1 integrin subunit, which when blocked by deoxymannojirimycin, reduced collagen binding. Collectively these data indicate that DDR1 regulates β1 integrin interactions with fibrillar collagen, which positively impacts the binding step of collagen phagocytosis and collagen remodeling.


Novel function of PERK as a mediator of force-induced apoptosis.
Induction of apoptosis by tensile forces is an important determinant of connective tissue destruction in osteoarthritis and periodontal diseases. We examined the role of molecular components of the unfolded protein response in force-induced apoptosis. Magnetic fields were used to apply tensile force through integrins to cultured fibroblasts bound with collagen-coated magnetite beads. Tensile force induced caspase 3 cleavage, DNA fragmentation, depolarization of mitochondria, and induction of CHOP10, all indicative of activation of apoptosis. Immunoblotting, immunocytochemistry, and release of Ca(2+) from the endoplasmic reticulum showed evidence for both physical and functional associations between bound beads and the endoplasmic reticulum. Force-induced apoptosis was not detected in PERK null cells, but reconstitution of wild-type PERK in PERK null cells restored the apoptotic response. Force-induced apoptosis did not require PKR, GCN2, eIF2alpha, or CHOP10. Furthermore, force more than 24 h did not activate other initiators of the unfolded protein response including IRE-1 and ATF6. However, force-induced activation of caspase 3 was dependent on caspase 9 but was independent of mitochondria. We conclude that force-induced apoptosis depends on a novel function of PERK that occurs in addition to its canonical role in the unfolded protein response.


Impaired cardiac function during postnatal hypoxia in rats exposed to nicotine prenatally: implications for perinatal morbidity and mortality, and for sudden infant death syndrome.
Maternal smoking correlates highly with parturitional/neonatal death including SIDS; nicotine exposure of fetal rats reproduces the increased mortality when animals are tested postnatally with hypoxia. In the current study, pregnant rats received nicotine infusions simulating smokers' plasma nicotine levels. At 1-2 days postpartum, the nicotine group displayed normal heart rates, EKG waveforms, and respiratory rates in normoxia. With hypoxia (5% O2, 10 min), controls showed initial tachycardia and a subsequent slight decline in heart rate; atrioventricular conduction was gradually impaired and repolarization abnormalities also appeared. The nicotine group showed no tachycardia and heart rate declined rapidly and precipitously within a few minutes after commencing hypoxia; otherwise, EKG alterations mimicked the controls'. Changes in respiration were identical in the two groups: initial tachypnea and subsequent decline. These results suggest that prenatal nicotine affects sinoatrial reactivity to hypoxia without impairing cardiac conduction per se. These mechanisms explain increased hypoxia-induced mortality in animals exposed to prenatal nicotine, and in man could account for increased morbidity/mortality and SIDS. Our results also indicate the need to test adverse effects of fetal drug exposure using conditions that challenge any given physiological system rather than relying solely on changes under basal conditions.


Fusarium kuroshium is the primary fungal symbiont of an ambrosia beetle, Euwallacea fornicatus, and can kill mango tree in Japan.
This study identifies fungi associated with Euwallacea fornicatus and determines whether these fungal species play the role of primary symbiont. E. fornicatus adults that emerged from the branches of infested trees in Okinawa main island, Japan, were collected and used to isolate fungi. Fusarium kuroshium and Penicillium citrinum were the most dominant fungal associates of females and males, respectively. F. kuroshium was much more frequently isolated from the head, including mycangia (fungus-carrying organs), of females than any other body parts. We inoculated healthy mango saplings with F. kuroshium or F. decemcellulare, both of which were symbionts of E. fornicatus females infesting mango trees. F. kuroshium decreased leaf stomatal conductance and rate of xylem sap-conduction area and increased length and area of xylem discoloration of the saplings, thereby weakening and killing some. These results suggest that F. kuroshium, a mycangial fungus of E. fornicatus, inhibits water flow in mango trees. This study is the first to report that F. kuroshium causes wilt disease in mango trees and that it is a primary fungal symbiont of E. fornicatus.


Using texture based features from the continuous wavelet transform of the electroretinogram to predict glaucoma.
Glaucoma is an optic neuropathy resulting in the progressive loss of retinal ganglion cells (RCGs). The photopic negative response (PhNR) of the electroretinogram (ERG) has been used to objectively measure RCG function. This study sought to explore whether the usage of textural features extracted from the continuous wavelet transform of the ERG combined with ERG amplitude markers were more effective at predicting glaucoma severity than using the ERG markers alone. One-hundred and three eyes of 55 participants were included in this study, who underwent ERG testing with a protocol targeted at the PhNR. Predictive models for glaucoma severity based on the estimated RGC count were fitted using multiadaptive regression splines (MARS). The models informed by a combination of amplitude markers and texture analysis had a better predictive performance; R2 = 0.492, compared to models informed by markers alone having an R2 = 0.349 (p = 0.009).Clinical Relevance- As a direct measure of retinal function, the ERG has potential to determine the health of RGCs. This study demonstrates there is additional data within the ERG available to clinicians, which has the potential to improve the diagnosis and management of glaucoma.


Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children.
Food allergy (FA) affects 2%-10% of US children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk and egg) in 2,759 US participants (1,315 children and 1,444 parents) from the Chicago Food Allergy Study, and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (P=5.5 × 10(-8)) and rs9275596 (P=6.8 × 10(-10)), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (P<5 × 10(-8)), and differential DNA methylation of the HLA-DQB1 and HLA-DRB1 genes partially mediate the identified SNP-PA associations. This study suggests that the HLA-DR and -DQ gene region probably poses significant genetic risk for PA.


Utilizing Chinese Admission Records for MACE Prediction of Acute Coronary Syndrome.
Clinical major adverse cardiovascular event (MACE) prediction of acute coronary syndrome (ACS) is important for a number of applications including physician decision support, quality of care assessment, and efficient healthcare service delivery on ACS patients. Admission records, as typical media to contain clinical information of patients at the early stage of their hospitalizations, provide significant potential to be explored for MACE prediction in a proactive manner. We propose a hybrid approach for MACE prediction by utilizing a large volume of admission records. Firstly, both a rule-based medical language processing method and a machine learning method (i.e., Conditional Random Fields (CRFs)) are developed to extract essential patient features from unstructured admission records. After that, state-of-the-art supervised machine learning algorithms are applied to construct MACE prediction models from data. We comparatively evaluate the performance of the proposed approach on a real clinical dataset consisting of 2930 ACS patient samples collected from a Chinese hospital. Our best model achieved 72% AUC in MACE prediction. In comparison of the performance between our models and two well-known ACS risk score tools, i.e., GRACE and TIMI, our learned models obtain better performances with a significant margin. Experimental results reveal that our approach can obtain competitive performance in MACE prediction. The comparison of classifiers indicates the proposed approach has a competitive generality with datasets extracted by different feature extraction methods. Furthermore, our MACE prediction model obtained a significant improvement by comparison with both GRACE and TIMI. It indicates that using admission records can effectively provide MACE prediction service for ACS patients at the early stage of their hospitalizations.


Ion-abrasion scanning electron microscopy reveals distorted liver mitochondrial morphology in murine methylmalonic acidemia.
Methylmalonic acidemia is a lethal inborn error of metabolism that causes mitochondrial impairment, multi-organ dysfunction and a shortened lifespan. Previous transmission electron microscope studies of thin sections from normal (Mut(+/+)) and diseased (Mut(-/-)) tissue found that the mitochondria appear to occupy a progressively larger volume of mutant cells with age, becoming megamitochondria. To assess changes in shape and volume of mitochondria resulting from the mutation, we carried out ion-abrasion scanning electron microscopy (IA-SEM), a method for 3D imaging that involves the iterative use of a focused gallium ion beam to abrade the surface of the specimen, and a scanning electron beam to image the newly exposed surface. Using IA-SEM, we show that mitochondria are more convoluted and have a broader distribution of sizes in the mutant tissue. Compared to normal cells, mitochondria from mutant cells have a larger surface-area-to-volume ratio, which can be attributed to their convoluted shape and not to their elongation or reduced volume. The 3D imaging approach and image analysis described here could therefore be useful as a diagnostic tool for the evaluation of disease progression in aberrant cells at resolutions higher than that currently achieved using confocal light microscopy.


Topographic Organization of the 'Third-Tier' Dorsomedial Visual Cortex in the Macaque.
The boundaries of the visual areas located anterior to V2 in the dorsomedial region of the macaque cortex remain contentious. This region is usually conceptualized as including two functional subdivisions: the dorsal component of area V3 (V3d) laterally and another area named the parietooccipital area (PO) or V6 medially. However, the nature of the putative border between V3d and PO/V6 has remained undefined. We recorded the receptive fields of multiunit clusters in male macaques and reconstructed the locations of recording sites using histological sections and computer-generated maps. Immediately adjacent to dorsomedial V2, we observed a representation of the lower contralateral quadrant that represented the vertical meridian at its rostral border. This region formed a simple eccentricity gradient from ∼<5° in the annectant gyrus to >60° in the parietooccipital medial sulcus. There was no topographic reversal where one would expect to find the border between V3d and PO/V6. Rather, near the midline, this lower quadrant map continued directly into a representation of the peripheral upper visual field without an intervening lower quadrant representation. Therefore, cortex previously assigned to the medial part of V3d and to PO/V6 forms a single map that includes parts of both quadrants. Together with previous observations that V3d and PO/V6 are densely myelinated relative to adjacent cortex and share similar input from V1, these results suggest that they are parts of a single area (for which we suggest the designation V6), which is distinct from the one forming the ventral component of the third-tier complex.SIGNIFICANCE STATEMENT The primate visual cortex has a large number of areas. Knowing the extent of each visual area and how they can be distinguished from each other is essential for the interpretation of experiments aimed at understanding visual processing. Currently, there are conflicting models of the organization of the dorsomedial visual cortex rostral to area V2 (one of the earliest stages of cortical processing of vision). By conducting large-scale electrophysiological recordings, we found that what were originally thought to be distinct areas in this region (dorsal V3 and the parietooccipital area PO/V6), together form a single map of the visual field. This will help to guide future functional studies and the interpretation of the outcomes of lesions involving the dorsal visual cortex.


[Characteristics of blood coagulation and rational hemostatic therapy of acute gastroduodenal hemorrhage].
The results of studies on the state of the coagulative and fibrinolytic system of blood in 78 patients with acute gastroduodenal hemorrhages are summarized. The causes of bleeding were as follows: ulcerous gastroduodenal disease -- in 38 cases, cancer of the stomach -- in 20, esophageal venous varices -- in 11 and erosive gastritis -- in 9. Some features of hemorrhage due to erosive gastritis, esophageal varices, ulcerous disease and gastric cancer are described.


Relationship between ERCC1 polymorphisms, disease progression, and survival in the Gynecologic Oncology Group Phase III Trial of intraperitoneal versus intravenous cisplatin and paclitaxel for stage III epithelial ovarian cancer.
We hypothesized that common polymorphisms in excision repair cross-complementation group 1 (ERCC1), involved in nucleotide excision repair of platinum-induced damage, would be associated with progression-free survival (PFS) and overall survival (OS) in women with optimally resected, stage III epithelial ovarian cancer (EOC) treated with cisplatin and paclitaxel (C+P). Single nucleotide polymorphism analysis was carried out by direct pyrosequencing at two sites (codon 118 and C8092A) in ERCC1 in leukocyte DNA from women who participated in the Gynecologic Oncology Group (GOG) phase III protocol-172 and were randomly assigned to intraperitoneal or intravenous C+P. ERCC1 genotyping was performed in 233 of the 429 women who participated in GOG-172. The genotype distribution at codon 118 was 17% with C/C, 43% with C/T, and 40% with T/T, and the genotype distribution at C8092A was 56% with C/C, 37% with C/A, and 7% with A/A. Adjusted Cox regression analysis revealed that the codon 118 polymorphism in ERCC1 was not significantly associated with disease progression or death. Women with the C8092A C/A or A/A genotypes compared with the C/C genotype had an increased risk of disease progression (hazard ratio [HR] = 1.44; 95% CI, 1.06 to 1.94; P = .018) and death (HR = 1.50; 95% CI, 1.07 to 2.09; P = .018). Median PFS and OS were 6 and 17 months shorter for women with the C8092A C/A or A/A genotypes versus the C/C genotype, respectively. Although the ERCC1 codon 118 polymorphism does not seem to be associated with clinical outcome, the C8092A polymorphism was an independent predictor of PFS and OS in women with optimally resected EOC.


Utility of coronary artery calcium scoring in the evaluation of patients with chest pain.
Although coronary artery calcium (CAC) scoring has an established role in risk-stratifying asymptomatic patients at intermediate risk of coronary heart disease (CHD), its utility in the evaluation of patients with chest pain is uncertain. We conducted a literature review of articles investigating the utility of: (1) CAC scoring in elective patients with indeterminate chest pain symptoms, (2) CAC as a "gatekeeper" in the triage of patients presenting to the emergency department (ED) with chest pain, and (3) the cost-effectiveness of the use of CAC scoring in the ED. We also evaluated the predictive accuracy of the absence of CAC in a pooled analysis of applicable studies. Only studies evaluating patients classified as low or intermediate risk were included. Low to intermediate risk was established by Framingham risk scores, Thrombolysis in Myocardial Infarction scores, Diamond-Forrester classification, or by the absence of typical angina symptoms, ischemic electrocardiogram, positive cardiac biomarkers, or a prior history of CHD. In our pooled analysis, the presence of any CAC resulted in a high sensitivity (range 70%-100%) for predicting the presence of obstructive coronary disease among symptomatic patients subsequently referred for coronary angiography. More importantly, a CAC score of 0 in low- and intermediate-risk ED populations with chest pain had a high negative predictive value (99.4%) for CHD events over an average follow-up of 21 months. CAC scoring also seems cost-effective in this population. Although further research is needed, carefully selected ED patients with a normal electrocardiogram, normal cardiac biomarkers, and CAC = 0 may be considered for early discharge without further testing.


Caring for the suffering: meeting the Ebola crisis responsibly.
The current Ebola virus epidemic in Western Africa appears to be spiraling out of control. The worst-case projections suggested that the unchecked spread could result in almost 1.4 million cases by the end of January 2015 with a case fatality rate of at least 50%. The United States and European nations have begun to respond in earnest with promises of supplies, isolation beds, and trained health care personnel in an effort to contain the epidemic and care for the sick. However, there is neither a vaccine nor specific treatment for Ebola infection, and therapy is ideally centered on supportive care. I have previously argued that the provision of palliative care is obligatory during an overwhelming health catastrophe, notably pandemic influenza. Since affected Ebola patients have best outcomes with technologically advanced intensive care--resources in scarce supply in the area--I suggest that the only acceptable approach to large numbers of very sick, dying, and suffering Ebola patients who overwhelm the resources available to successfully manage them is effective palliative care. However, this could hasten death in this vulnerable population and hence, while ethically and medically justifiable, is not without social risk.


Refinement and reduction in animal experimentation: options for new imaging techniques.
Attempts to substitute animal experiments with in vitro or in silico methods were of limited success when complex (regulatory) processes, e.g. of the cardiovascular, metabolic or neuronal system, were to be analysed. Consequently, strategies to reduce the number of and the burden placed on experimental animals in these fields of research are required. One option consists in the application of non-invasive imaging techniques like (functional) magnetic resonance imaging ((f)MRI), positron emission tomography (PET), and optical imaging (OI). All these methods allow for the observation of functional changes within the body of e.g. genetically modified animals without pain, suffering or (premature) termination. The use of these methods has now reached new dimensions of resolution and precision. With this article we would like to demonstrate a few options of these techniques. We hope that our enthusiasm becomes contagious, thus motivating more scientists to make use of the still expensive equipment which has become available in "small animal imaging" centres. On the basis of four examples--three from our group--we would like to highlight some merits of the new technologies.


The 13C hyperpolarized pyruvate generated by ParaHydrogen detects the response of the heart to altered metabolism in real time.
Many imaging methods have been proposed to act as surrogate markers of organ damage, yet for many candidates the essential biomarkers characteristics of the injured organ have not yet been described. Hyperpolarized [1-13C]pyruvate allows real time monitoring of metabolism in vivo. ParaHydrogen Induced Polarization (PHIP) is a portable, cost effective technique able to generate 13C MR hyperpolarized molecules within seconds. The introduction of the Side Arm Hydrogenation (SAH) strategy offered a way to widen the field of PHIP generated systems and to make this approach competitive with the currently applied dissolution-DNP (Dynamic Nuclear Polarization) method. Herein, we describe the first in vivo metabolic imaging study using the PHIP-SAH hyperpolarized [1-13C]pyruvate. In vivo maps of pyruvate and of its metabolic product lactate have been acquired on a 1 T MRI scanner. By comparing pyruvate/lactate 13C label exchange rate in a mouse model of dilated cardiomyopathy, it has been found that the metabolic dysfunction occurring in the cardiac muscle of the diseased mice can be detected well before the disease can be assessed by echocardiographic investigations.


Risk factors for progression of aortic atheroma in stroke and transient ischemic attack patients.
Aortic atheroma is an independent risk factor for stroke and undergoes temporal progression. Clinical and risk factor associations of such progression are unknown. Hyperhomocysteinemia has been linked with atherosclerosis, including that in the cerebral vasculature. This study investigated associations between elevated homocysteine levels and other stroke vascular risk factors and the risk of aortic atheroma progression in patients with cerebrovascular disease. Fifty-seven stroke and 21 transient ischemic attack patients underwent multiplanar transesophageal echocardiograms within 1 month of symptom onset and again at 9 months. Aortic atheroma was graded and stratified by use of existing criteria. Stroke risk factors; use of anticoagulant, antiplatelet, and hypolipidemic drugs; and clinical and etiological subtypes of stroke were recorded and compared in patients stratified for the presence or absence of aortic atheroma progression. Of the 78, 29 (37%) progressed, 32 (41%) remained unchanged, and 17 (22%) regressed. Progression was most marked at the aortic arch (P=0.005), followed by the ascending segment (P<0.04). In nearly two thirds of the patients in whom aortic atheroma remained unchanged over 9 months, no atheroma was evident on baseline transesophageal echocardiogram. Only homocysteine levels > or =14.0 micromol/L (P=0.02), total anterior cerebral infarct (P=0.02), and large-artery atherosclerosis (P=0.005) significantly correlated with progression. Among vascular risk factors, elevated homocysteine levels are associated with aortic atheroma progression. Stroke and transient ischemic attack patients with aortic atheroma should undergo assessment of homocysteine levels, which, if elevated, may be treated with vitamins in an effort to arrest aortic atheroma progression.


Bioconversion of Chicken Feather Meal by Aspergillus niger: Simultaneous Enzymes Production Using a Cost-Effective Feedstock Under Solid State Fermentation.
This study reported for the first time the simultaneous production of hydrolytic enzymes by Aspergillus niger under solid state fermentation using chicken feather meal as substrate. The effect of some culture parameters for production of protease, lipase, phytase and keratinase enzymes was evaluated using a central composite rotatable design. The results obtained demonstrated that the independent variables initial moisture of the culture medium and incubation temperature presented as highly significant on the enzymes production. The production of protease and lipase followed a similar profile, in which the highest values of enzymatic activities were detected after 48 h of fermentation. The conduction of the fermentative process using an initial moisture of 50%, 30 °C as incubation temperature and supplementation of the feather meal with 15% wheat bran resulted in higher yields of protease (> 300 U g-1) and lipase (> 90 U g-1) after 48 h and satisfactory values of phytase activity (> 70 U g-1) after 72 h. No significant effects of the independent variables on keratinase production were observed. However, under the selected conditions for the other enzymes, keratinase production reached values higher than 13 U g-1 after 72 h fermentation. Thus, our work contributed to the proposal of an alternative process for the simultaneous production of proteases, lipases, phytases and keratinases in a single and simplified process using chicken feather meal.


The role of spatial and temporal heterogeneity and competition in structuring trematode communities in the great pond snail, Lymnaea stagnalis (L.).
We assessed how spatial and temporal heterogeneity and competition structure larval trematode communities in the pulmonate snail Lymnaea stagnalis . To postulate a dominance hierarchy, mark-release-recapture was used to monitor replacements of trematode species within snails over time. In addition, we sampled the trematode community in snails in different ponds in 3 consecutive years. A total of 7,623 snails (10,382 capture events) was sampled in 7 fishponds in the Jindřichův Hradec and Třeboň areas in South Bohemia (Czech Republic) from August 2006 to October 2008. Overall, 39% of snails were infected by a community of 14 trematode species; 7% of snails were infected with more than 1 trematode species (constituting 16 double- and 4 triple-species combinations). Results of the null-model analyses suggested that spatial heterogeneity in recruitment among ponds isolated trematode species from each other, whereas seasonal pulses in recruitment increased species interactions in some ponds. Competitive exclusion among trematodes led to a rarity of multiple infections compared to null-model expectations. Competitive relationships among trematode species were hypothesized as a dominance hierarchy based on direct evidence of replacement and invasion and on indirect evidence. Seven top dominant species with putatively similar competitive abilities (6 rediae and 1 sporocyst species) reduced the prevalence of the other trematode species developing in sporocysts only.


Cross-cultural adaptation and validation of the Chinese version of the Malocclusion Impact Scale for Early Childhood (MIS-EC/C).
The Malocclusion Impact Scale for Early Childhood (MIS-EC) is a newly developed questionnaire used to measure the parental perceptions of the impact of malocclusion on oral health-related quality of life (OHRQoL) of preschool children aged 3-5 years. This study describes the cross-cultural adaptation and validation of the MIS-EC questionnaire into Chinese version (MIS-EC/C). The MIS-EC/C was developed in accordance with international standards. The scale was then evaluated in a cross-sectional study comprising 210 preschool children aged 3-5 years. The reliability of the MIS-EC/C was tested using internal consistency and test-retest reliability analyses. Cross-cultural validity, discriminant validity and convergent validity were tested. The Cronbach's α value and intraclass correlation coefficient (ICC) value for the MIS-EC/C were 0.943 and 0.873, respectively. Confirmatory factor analysis indicated that the fitting indicators of the two-factor model all reached the standard. The MIS-EC/C can differentiate preschool children with malocclusion from those without malocclusion. In addition, there is a good relationship between the MIS-EC/C and the general oral health question. The MIS-EC/C is a reliable and effective assessment tool for assessing the effect of malocclusion on the OHRQoL of preschool children in China.


Optic nerve head blood flow in chronic experimental glaucoma.
We used the tritiated iodoantipyrine method to estimate blood flow in the retina, optic nerve head, and retrobulbar optic nerve in monkey eyes. Twelve eyes with short-term intraocular pressure (IOP) elevation and nine eyes with long-term (up to 20 months) IOP elevation were compared with their fellow normal eyes. The eyes with long-term glaucoma were staged for degree of optic nerve damage according to disc cup size, nerve fiber layer atrophy, and histologic estimates of the remaining number of nerve fibers. At normal IOP levels, there were only minor differences in blood flow in the superior, inferior, and middle nerve head sections. In eyes with short-term IOP elevation, nerve head blood flow was normal, unless IOP exceeded 75 mm Hg. Above this level, a progressive decrease in nerve head blood flow was measured. Mean blood flow in the nerve head of eyes with long-term glaucoma was not significantly different from that in the normal fellow eyes. Some animals had small increases in blood flow, while others had small decreases. These differences from normal did not correlate with the amount or location of optic nerve damage. Our data do not support decreased blood flow as part of the pathogenesis of long-term experimental glaucoma.


Temozolomide and whole brain irradiation in melanoma metastatic to the brain: a phase II trial of the Cytokine Working Group.
To evaluate the antitumor effects and toxicities of whole brain irradiation (WBI) with temozolomide (TMZ) administered by prolonged oral dosing in patients with melanoma metastatic to the brain. Patients with melanoma metastatic to the central nervous system (CNS) have an extremely poor prognosis and appear to benefit little from WBI. TMZ is an alkylating agent chemically similar to dacarbazine (DTIC) with good oral bioavailability and CNS penetration. TMZ has broad preclinical antitumor activity which in melanoma is comparable to that of DTIC. The combination of TMZ and WBI may provide enhanced antitumor activity against CNS metastasis from melanoma. Patients with measurable CNS metastases with or without systemic disease were treated with WBI, 30 Gray over ten fractions (days 1-5 and 8-12). TMZ, 75 mg small middle dotm(2 small middle dot)day, was started on day 1, continued daily for 6 weeks and repeated every 10 weeks. Thirty-one patients were treated. There was one CNS complete response of 4.5 months and two CNS partial responses of 2 months and 7 months duration; the latter patient also had a 4-month complete remission of systemic metastases. Toxicities were limited to a single episode of grade 3 transaminase elevation and two episodes of grade 3 neutropenia, one complicated by fatal sepsis. The median progression-free interval for both CNS and extracranial sites was 2 months (range 1 week-11 months), and median survival 6 months (range 2-12 months). WBI has lower than expected activity in CNS metastasis of malignant melanoma. Although TMZ can be safely administered with WBI, the combination has limited anti-tumor activity.


Comparison of the FeKal CON-Trate system with the formalin-ethyl acetate technique for detection of intestinal parasites.
The ability of the FeKal CON-Trate system (Trend Scientific, Minneapolis, Minn.) to recover parasite ova, cysts, or larvae from 300 fecal specimens was compared with that of the Formalin-ethyl acetate sedimentation technique. One hundred stool samples had previously been determined to contain 129 parasite forms. The FeKal system detected 127 parasites (sensitivity, 98.4%), and the Formalin-ethyl acetate sedimentation technique detected 125 parasites (sensitivity, 96.9%). Higher counts of parasite forms were obtained for 11 of 14 species of parasites in specimens prepared by the FeKal system. Four specimens were negative by the Formalin-ethyl acetate method and two by the FeKal system. These false-negative observations occurred in specimens with low counts of parasites. There were no false-positive results.


Whisker motor cortex reorganization after superior colliculus output suppression in adult rats.
The effect of unilateral superior colliculus (SC) output suppression on the ipsilateral whisker motor cortex (WMC) was studied at different time points after tetrodotoxin and quinolinic acid injections, in adult rats. The WMC output was assessed by mapping the movement evoked by intracortical microstimulation (ICMS) and by recording the ICMS-evoked electromyographic (EMG) responses from contralateral whisker muscles. At 1 h after SC injections, the WMC showed: (i) a strong decrease in contralateral whisker sites, (ii) a strong increase in ipsilateral whisker sites and in ineffective sites, and (iii) a strong increase in threshold current values. At 6 h after injections, the WMC size had shrunk to 60% of the control value and forelimb representation had expanded into the lateral part of the normal WMC. Thereafter, the size of the WMC recovered, returning to nearly normal 12 h later (94% of control) and persisted unchanged over time (1-3 weeks). The ICMS-evoked EMG response area decreased at 1 h after SC lesion and had recovered its baseline value 12 h later. Conversely, the latency of ICMS-evoked EMG responses had increased by 1 h and continued to increase for as long as 3 weeks following the lesion. These findings provide physiological evidence that SC output suppression persistently withdrew the direct excitatory drive from whisker motoneurons and induced changes in the WMC. We suggest that the changes in the WMC are a form of reversible short-term reorganization that is induced by SC lesion. The persistent latency increase in the ICMS-evoked EMG response suggested that the recovery of basic WMC excitability did not take place with the recovery of normal explorative behaviour.


The effect of medical student feedback about resident teaching on resident teaching identity: a randomized controlled trial.
Residents often teach medical students, other residents, and patients. However, few residents get feedback about their teaching. This study's objective was to determine if feedback from medical students increases resident teaching identity. This was a stratified, single blinded, randomized controlled trial of an educational intervention. Residents were stratified based on year of residency and then randomized to receive feedback by medical students or not. Medical students evaluated resident teaching effectiveness by ranking resident ability to apply the five microskills for clinical teaching and to role model being an effective clinician. Residents were surveyed to determine their level of teacher identity before and after the intervention. Allocation concealment and intention to treat principles were used. All residents (n=32) that met inclusion criteria participated with complete response rate to both pre-intervention and post-intervention surveys. There was no difference in teaching identity between residents who received feedback and those who did not, except in one subscale of the Teacher Identity Scale-global teaching identity, where residents who received medical student feedback scored lower. There was no difference between intervention and control group in resident teaching identity over time. The residents found feedback important. This was a randomized controlled trial with strong methodology that helps advance understanding of the importance of medical student feedback on resident teaching.


[Experience with the application of sinuforte as starting monotherapy of acute rhinosinusitis associated with exudative otitis media in children and adolescents].
A number of clinical cases of inflammatory changes in the nasopharynx rhinosinusitis apply to the area of auditory tube with the development of exudative otitis media. The objective of the present simple open study was to estimate the effectiveness and safety of the treatment of moderately severe acute rhinosinusitis associated with exudative otitis media in the children and adolescents with the use of sinuforte as starting monotherapy. The study included 47 patients at the age from 7 to 15 years. The results obtained indicate that the effectiveness of this treatment is comparable in terms of duration with that of traditional therapy. However, the use of sinuforte as initial monotherapy has some advantages over the traditional modality in that it reduces the drug loading and offers a simple scheme of the treatment with proven safety. Taken together, these advantages provide a conclusive argument in favour of selecting Sinuforte as initial therapy of the above ENT pathology.


Estimation of percentage body fat in 6- to 13-year-old children by skinfold thickness, body mass index and waist circumference.
We evaluated the accuracy of skinfold thicknesses, BMI and waist circumference for the prediction of percentage body fat (PBF) in a representative sample of 372 Swiss children aged 6-13 years. PBF was measured using dual-energy X-ray absorptiometry. On the basis of a preliminary bootstrap selection of predictors, seven regression models were evaluated. All models included sex, age and pubertal stage plus one of the following predictors: (1) log-transformed triceps skinfold (logTSF); (2) logTSF and waist circumference; (3) log-transformed sum of triceps and subscapular skinfolds (logSF2); (4) log-transformed sum of triceps, biceps, subscapular and supra-iliac skinfolds (logSF4); (5) BMI; (6) waist circumference; (7) BMI and waist circumference. The adjusted determination coefficient (R² adj) and the root mean squared error (RMSE; kg) were calculated for each model. LogSF4 (R² adj 0.85; RMSE 2.35) and logSF2 (R² adj 0.82; RMSE 2.54) were similarly accurate at predicting PBF and superior to logTSF (R² adj 0.75; RMSE 3.02), logTSF combined with waist circumference (R² adj 0.78; RMSE 2.85), BMI (R² adj 0.62; RMSE 3.73), waist circumference (R² adj 0.58; RMSE 3.89), and BMI combined with waist circumference (R² adj 0.63; RMSE 3.66) (P < 0.001 for all values of R² adj). The finding that logSF4 was only modestly superior to logSF2 and that logTSF was better than BMI and waist circumference at predicting PBF has important implications for paediatric epidemiological studies aimed at disentangling the effect of body fat on health outcomes.


Genome-Wide Identification and Comprehensive Analysis of the GASA Gene Family in Peanuts (Arachis hypogaea L.) under Abiotic Stress.
Peanut (Arachis hypogaea L.) is a globally cultivated crop of significant economic and nutritional importance. The role of gibberellic-acid-stimulated Arabidopsis (GASA) family genes is well established in plant growth, development, and biotic and abiotic stress responses. However, there is a gap in understanding the function of GASA proteins in cultivated peanuts, particularly in response to abiotic stresses such as drought and salinity. Thus, we conducted comprehensive in silico analyses to identify and verify the existence of 40 GASA genes (termed AhGASA) in cultivated peanuts. Subsequently, we conducted biological experiments and performed expression analyses of selected AhGASA genes to elucidate their potential regulatory roles in response to drought and salinity. Phylogenetic analysis revealed that AhGASA genes could be categorized into four distinct subfamilies. Under normal growth conditions, selected AhGASA genes exhibited varying expressions in young peanut seedling leaves, stems, and roots tissues. Notably, our findings indicate that certain AhGASA genes were downregulated under drought stress but upregulated under salt stress. These results suggest that specific AhGASA genes are involved in the regulation of salt or drought stress. Further functional characterization of the upregulated genes under both drought and salt stress will be essential to confirm their regulatory roles in this context. Overall, our findings provide compelling evidence of the involvement of AhGASA genes in the mechanisms of stress tolerance in cultivated peanuts. This study enhances our understanding of the functions of AhGASA genes in response to abiotic stress and lays the groundwork for future investigations into the molecular characterization of AhGASA genes.


Short leg correction: a clinical trial of radiographic vs. non-radiographic procedures.
Visual leg length insufficiency detection and correction is compared with established radiographic procedures on 41 consecutive patients presenting to a chiropractic clinic with low back pain. It is commonly accepted that the most accurate procedure of short leg demonstration is the standing X ray. Visual correction, as described by Rene Cailliet, uses three anatomical points of reference: a) iliac crest levelness, b) vertical appraisal of the spine from the sacral base (the spine should be perpendicular to the sacral base) and c) levelness of the posterosuperior iliac spine (PSIS) dimples. Lifts of varying thickness were placed under the foot of the short leg in both leg length corrective procedures. This study found that the visual method of measurement did not differ significantly from the X-ray method of measurement for leg length insufficiency. Further, it was found that when comparing those in which the visual measure was less than the X-ray measure and those in which the visual measure was greater, there was a significant relationship between visual and X-ray measures. Eta (eta 2) demonstrates that there is a very strong relationship between visual and X-ray methods of measurement. A review of the literature is presented regarding the correlation of leg length insufficiency and musculoskeletal disorders, as well as the discrepancy required to alter biomechanical properties of the trunk and lower extremity.


How do mental health practitioners operationalise cultural competency in everyday practice? A qualitative analysis.
Despite continued policy and research emphasis to deliver culturally competent mental healthcare, there is: (1) limited evidence about what frontline practitioners consider to be culturally competent care and; (2) what helps or hinders them in delivering such care in their everyday practice. The aims of this article are to address these gaps. Qualitative in-depth interviews were conducted with 20 mental health practitioners working with immigrant patients to explore their understandings and experiences of culturally competent care. Interviews were conducted between September 2015 and February 2016 in the state of Victoria, Australia. Data were thematically analysed. There were common understandings of cultural competence but its operationalisation differed by profession, health setting, locality, and years of experience; urban psychiatrists were more functional in their approach and authoritarian in their communication with patients compared to allied health staff in non-specialist mental health settings, in rural areas, with less years of experience. Different methods of operationalising cultural competence translated into complex ways of building cultural concordance with patients, also influenced by health practitioners' own cultural background and cultural exposures. Limited access to interpreters and organisational apathy remain barriers to promoting cultural competency whereas organisational support, personal motivation, and professional resilience remain critical facilitators to sustaining cultural competency in everyday practice. While there is need for widespread cultural competence teaching to all mental health professionals, this training must be specific to different professional needs, health settings, and localities of practice (rural or urban). Experiential teaching at tertiary level or professional development programs may provide an avenue to improve the status quo but a 'one-size-fits-all' model is unlikely to work.


Ten-year trends in the health of young children in California: 2003 to 2011-2012.
This policy brief presents 10-year trends in several key health and wellness indicators for children ages 0-5 in California. These indicators are health insurance coverage; source of medical care; dental visits; overweight-for-age; parents singing and reading to their child and going out with the child; and preschool attendance. The data are from the California Health Interview Survey (CHIS), the largest state health survey in the U.S. The survey gathers information on a range of health behaviors and health conditions, as well as on access to health care among children, adolescents, and adults in California. A number of these key indicators are compared by income and by racial/ethnic group. This policy brief covers the years 2003 to 2011-2012, a period in which public health efforts for children focused on childhood obesity and improved nutrition, access to low-cost and free dental services, and the expansion of children's health insurance programs. CHIS data show improvement in health insurance coverage and access to dental services for low-income children over the 10-year period. However, the percentage of children who were overweight for their age remained unchanged among those in households with incomes below 200 percent of the federal poverty level (FPL). In terms of measures associated with school readiness, preschool attendance dropped overall between 2003 and 2011-2012, but the proportions of parents who sang, read, and went out with their children every day increased significantly during the 10-year period.


Cysticercosis--review of 230 patients.
Two hundred thirty patients with cysticercosis were reviewed. Investigation with CT scan has led to a more detailed understanding of the natural history of human infestation which is essential to the evaluation of new pharmacological and neurosurgical treatments. In contrast to reports emphasizing the need to extirpate all intraventricular cysts, many of our patients needed only ventricular shunt implantation. The ability to evaluate and reevaluate hydrocephalus by CT scan permitted comfortable use of ventricular shunt insertion as the only treatment. Nevertheless, cysts in the fourth ventricle should nearly always be extirpated, because these cysts, by their mass effect, may cause herniation even after shunt implantation. Serious morbidity and death occur chiefly in patients who develop hydrocephalus from intraventricular and basilar infestation. It is unlikely that praziquantel will be effective in patients who present with symptoms of hydrocephalus.


[Endometriosis: physiopathology and investigation lines (part two)].
Sampson's menstrual reflux theory (1927) is widely accepted as an explanation of endometriosis physiopathology, it proposes five basic necessary processes to its development: adhesion, invasion, recruitment, angiogenesis and proliferation. Several factors and physiologic processes are necessary for the survival and growth of endometrial tissue. Clinical manifestations of these disease are: dysmenorrhoea, dyspareunia, and peritoneal adhesions, that with other findings reveal an inflammatory process that requires cytokines, macrophages, NK cells, lymphocytes and prostaglandins whose qualitative functions may be compromised or may contribute to the peripheral generation of estrogens. Angiogenesis benefits the development of these endometrial tissue foci and probably stimulates several vascular growth factors, and sexual steroids. Endocrine factors are capital for this entity, as is demonstrated by the presence of estrogen receptors in macrophages, fibroblasts and endometrium among others, as well as the clinical symptoms control trough the blockage of the hypothalamus-pituitary-ovary axis. Studies on the genetic and antioxidant factors have revealed key points that may be helpful in determining a proper diagnosis and treatment for endometriosis.


Rerouting the traffic from a virus perspective.
Viruses are important human and animal pathogens causing disease that affect global health and the economy. One outcome of many virus infections is the regulation of cellular trafficking machinery. Viral proteins recruit and interact with cellular trafficking proteins to divert the normal trafficking of key proteins or to induce the formation of novel membrane structures in the host cell. These alterations often increase replication efficiency by mislocalizing immune regulators or restriction factors ot by creating platforms for replication and assembly of new virus particles. Our knowledge of how viruses interact with the cellular trafficking machinery is still limited and furthering this understanding will be important for the future development of prophylactic and therapeutic treatments. This review provides a glimpse of the types of interplay between viral and cellular factors that result in a disruption of cellular trafficking or modifications to cellular membranes.


Oral masses in African pygmy hedgehogs.
African pygmy hedgehogs (Atelerix albiventris) frequently develop oral neoplasms, and most of these neoplasms are malignant. We characterized oral masses detected in hedgehogs at clinical examination. During a 1-y period, we diagnosed oral cavity masses in 27 privately owned hedgehogs; 16 were female and 11 were male, with ages of 2-7 y (mean: 4.3 y). Eight masses were non-neoplastic and were diagnosed as gingival hyperplasia (GH). Nineteen masses were neoplastic, of which 17 were squamous cell carcinomas (SCCs) and 2 were mesenchymal tumors (1 spindle cell tumor of probable neural origin, and 1 hemangiosarcoma). The GHs were noninvasive, exophytic, and did not recur after surgical excision. The SCCs were highly invasive tumors that induced facial deformation and were located in the caudal portion of the oral cavity, with 12 of them arising from the right-caudal maxilla. Thus, clinical signs, growth pattern, and anatomic location can be used to suspect a diagnosis of SCC among the other possible diagnoses, such as GH, in this location. However, histopathology is necessary for confirmation. Also, hemangiosarcoma should be considered among the differential diagnoses.


Genomic annotation for vaccine target identification and immunoinformatics-guided multi-epitope-based vaccine design against Songling virus through screening its whole genome encoded proteins.
Songling virus (SGLV), a newly discovered tick-borne orthonairovirus, was recently identified in human spleen tissue. It exhibits cytopathic effects in human hepatoma cells and is associated with clinical symptoms including headache, fever, depression, fatigue, and dizziness, but no treatments or vaccines exist for this pathogenic virus. In the current study, immunoinformatics techniques were employed to identify potential vaccine targets within SGLV by comprehensively analyzing SGLV proteins. Four proteins were chosen based on specific thresholds to identify B-cell and T-cell epitopes, validated through IFN-γ epitopes. Six overlap MHC-I, MHC-II, and B cell epitopes were chosen to design a comprehensive vaccine candidate, ensuring 100% global coverage. These structures were paired with different adjuvants for broader protection against international strains. Vaccine constructions' 3D models were high-quality and validated by structural analysis. After molecular docking, SGLV-V4 was selected for further research due to its lowest binding energy (-66.26 kcal/mol) and its suitable immunological and physiochemical properties. The vaccine gene is expressed significantly in E. coli bacteria through in silico cloning. Immunological research and MD simulations supported its molecular stability and robust immune response within the host cell. These findings can potentially be used in designing safer and more effective experimental SGLV-V4 vaccines.


Alport syndrome.
Alport syndrome is an oculo-renal syndrome characterized by a triad of clinical findings consisting of hemorrhagic nephritis, sensorineural hearing loss and characteristic ocular findings. We report a young male patient who presented with painless diminution of vision associated with hearing loss. The importance of ophthalmic evaluation for suspecting the disease is highlighted.


Phosphorylation of histone and histone-like proteins by aurora kinases during mitosis.
Successful cell division requires that daughter cells inherit not only a complete set of chromosomes, but also only one centrosome, and similar amounts of organelles and cytoplasmic components. The different mitotic processes are driven by cell cycle-regulated protein kinases and phosphatases and their fidelity is closely monitored by a number of checkpoint mechanisms. Histone H3 is phosphorylated during mitosis, but the kinases involved were not known until recently. Recent work has revealed that Aurora kinases are required for mitotic phosphorylation of histone H3 and of its centromeric variant CENP-A. This finding has stimulated functional studies of the role(s) of Aurora kinases and H3 phosphorylation during mitosis, which are reviewed in this chapter.


Modelling the Impact of Reducing Ultra-Processed Foods Based on the NOVA Classification in Australian Women of Reproductive Age.
Women of reproductive age have a high proportion of overweight/obesity and an overall poor nutritional intake and diet quality. Nutritional modelling is a method to forecast potential changes in nutrition composition that may offer feasible and realistic changes to dietary intake. This study uses simulation modelling to estimate feasible population improvements in dietary profile by reducing ultra-processed food (UPF) consumption in Australian women of reproductive age. The simulation used weighted data from the most recent 2011-2012 National Nutrition and Physical Activity Survey. A total of 2749 women aged 19-50 years was included, and 5740 foods were examined. The highest daily energy, saturated fat, and added sugar and sodium came from UPF. Reducing UPF by 50% decreased energy intake by 22%, and saturated fat, added sugar, sodium, and alcohol by 10-39%. Reducing UPF by 50% and increasing unprocessed or minimally processed foods by 25% led to a lower estimated reduction in energy and greater estimated reductions in saturated fat and sodium. Replacement of 50% UPF with 75% of unprocessed or minimally processed foods led to smaller estimated reductions in energy and nutrients. Our results provide insight as to the potential impact of population reductions in UPF, but also increasing intake of unprocessed or minimally processed foods, which may be the most feasible strategy for improved nutritional intake.


[An analysis of the referrals to specialist consultations made in a health center].
The study of referrals from primary care areas permits the evaluation of health care in this level and reveals the educational requirements of the specialists in family medicine. Between January and April 1988 a prospective study was carried out to evaluate the referrals to the second level of care in the health center V Centenario. In 27,657 visits 1,906 referrals to the different specialties were ordered, which represents a rate of 6.89%. The most commonly consulted specialties were gynecology (18.94% of the overall referrals), ophthalmology (18.04%) and traumatology (16.10%). Psychiatry (1.41%), neurology (1.31%) and endocrinology (1.41%) were the specialties with the lowest referral rates. We compared our results with those from other authors and we have calculated what influence would be exerted on the second level of care if all primary care physicians had similar referral rates to those obtained in our center.


Human motor cortical activity recorded with Micro-ECoG electrodes, during individual finger movements.
In this study human motor cortical activity was recorded with a customized micro-ECoG grid during individual finger movements. The quality of the recorded neural signals was characterized in the frequency domain from three different perspectives: (1) coherence between neural signals recorded from different electrodes, (2) modulation of neural signals by finger movement, and (3) accuracy of finger movement decoding. It was found that, for the high frequency band (60-120 Hz), coherence between neighboring micro-ECoG electrodes was 0.3. In addition, the high frequency band showed significant modulation by finger movement both temporally and spatially, and a classification accuracy of 73% (chance level: 20%) was achieved for individual finger movement using neural signals recorded from the micro-ECoG grid. These results suggest that the micro-ECoG grid presented here offers sufficient spatial and temporal resolution for the development of minimally-invasive brain-computer interface applications.


A Mn-doped Ni2P nanosheet array: an efficient and durable hydrogen evolution reaction electrocatalyst in alkaline media.
Developing earth-abundant and high-performance electrocatalysts toward the alkaline hydrogen evolution reaction (HER) is highly desired. In this communication, we report a Mn-doped Ni2P nanosheet array on nickel foam (Mn-Ni2P/NF) as a high-efficiency electrocatalyst for the HER in alkaline solutions. This Mn-Ni2P/NF can drive 20 mA cm-2 at an overpotential of 103 mV in 1.0 M KOH, which is 82 mV less than that for Ni2P/NF. In addition, it also demonstrates excellent long-term electrochemical durability for at least 25 h. This work offers us a promising catalyst material for water-splitting devices for large-scale production of hydrogen fuels.


Probiotics for maintaining remission of ulcerative colitis in adults.
To evaluate evidence for probiotic efficacy for maintaining remission of ulcerative colitis (UC) in adults. A MEDLINE search (1948-November 2009) was conducted using ulcerative colitis and probiotics as terms for identifying pertinent studies. Search limits included English language and humans. Additional information was obtained from bibliographies. Prospective trials published in English and conducted in adults were included. Two open-label and 3 double-blind randomized trials evaluated probiotic efficacy for maintaining remission of UC. Clinical and surrogate markers for maintaining remission of UC were assessed. A relationship between immune response and gastrointestinal microbials appears to be involved in the mechanism of UC. Trial results comparing the probiotic Escherichia coli Nissle 1917 to mesalazine have reported equivalent rates of UC relapse. Treatment with Lactobacillus rhamnosus GG strain alone or in combination with mesalazine resulted in a nonsignificant odds ratio decrease for relapse and a significant increase in time to relapse compared to treatment with mesalazine alone. Additionally, bifidobacteria-fermented milk-supplemented patients had significant reductions in UC exacerbations when compared to nonsupplemented patients. Probiotics were well tolerated, with adverse event rates similar between treatments. Studies evaluating probiotics for maintaining remission of UC are limited by trial design and use of different probiotics with variable bacterial contents. Thus, questions remain regarding optimal probiotic, dosing, specific patient populations, and placement in therapy. To answer these questions, large, randomized, controlled trials need to be conducted before probiotics can be routinely recommended for maintaining remission of UC.


One Size Does Not Fit All: Venous Thromboembolism Prophylaxis in Colorectal Cancer.
Venous thromboembolisms (VTEs) in patients who have undergone a colorectal cancer operation increases morbidity and mortality, lengthens recovery time, and are costly. The current common standard is a 28-day prophylactic regimen of 40 mg enoxaparin daily. This study aims to examine the variability in prophylaxis discharge prescriptions at one institution, report 30-day postoperative incidence of venous thromboembolisms and bleeding, and to offer a new protocol for VTE prophylaxis in postoperative patients. This retrospective case series occurred at Abington-Jefferson Health Hospital in Abington, PA. The electronic medical record was searched for patients who underwent an operation for colorectal cancer from October 2019 to mid-March 2020 and all discharge prophylaxis regimens were recorded and patient demographics were analyzed. Outcomes were measured by rate of VTEs and postoperative complications such as bleeding, transfusions, re-admission, and intensive care admission in the 30-day postoperative period. Eighteen of 57 patients received a medication besides 40 mg of enoxaparin daily. These 18 patients were divided into six different sub-groups of various prophylaxis regimens. No patients developed a venous thromboembolism. Four of 18 patients experienced postoperative bleeding complications. Patients with similar pre-operative comorbidities have various venous thromboembolism perioperative prophylaxis regimens prescribed. Despite prescription variations, VTE rates remain negligible. Patients with different comorbid conditions may require alterations to the traditionally prescribed 40 mg enoxaparin daily. Upon discharge, aspirin 81 mg with 40 mg of enoxaparin daily for high-risk patients shows benefits, but requires further investigation.