Induced heterodimerization and purification of two target proteins by a synthetic coiled-coil tag.
A synthetic de novo designed heterodimeric coiled-coil was used to copurify two target fluorescent proteins, Venus and enhanced cyan fluorescent protein (ECFP). The coiled-coil consists of two 21-amino acid repetitive sequences, (EIAALEK)(3) and (KIAALKE)(3), named E3 and K3, respectively. These sequences were fused to the C-termini of ECFP or Venus followed by either a strep- or a his-tag, respectively, for affinity purification. Mixed lysates of Venus-K3 and ECFP-E3 were subjected to consecutive affinity purification and showed highly specific association between the coiled-coil pair by SDS-PAGE, gel filtration, isothermal titration calorimetry (ITC), and fluorescence resonance energy transfer (FRET). The tagged proteins eluted as heterodimers at the concentrations tested. FRET analysis further showed that the coiled-coil pair was stable in buffers commonly used for protein purification, including those containing high salt concentration and detergent. This study shows that the E3/K3 pair is very well suited for the copurification of two target proteins expressed in vivo because of its high specificity: it forms exclusively heterodimers in solution, it does not interact with any cellular proteins and it is stable under different buffer conditions.


Clinical experiences with drospirenone: from reproductive to postmenopausal years.
To review the scientific publications concerning the clinical use of drospirenone (DRSP) as the progestin in combined oral contraceptives (OCs), and as hormone treatment for menopause. This is a retrospective study of published information concerning DRSP retrieved from both a PubMed and a personal search. DRSP is a progestin with antimineralocorticoid and antiandrogenic activities that confer special clinical relevance. The OC containing ethinyl estradiol (either 30 or 20 microg/day) and DRSP (3 mg) has been shown to be highly efficacious and to provide safety equivalent to that of other OC formulations. These OCs appear to improve many of the symptoms associated with premenstrual complaints and dysphoric disorders, including negative mood, water retention and increased appetite. The comparative safety and efficacy of newer OC formulations is difficult to establish since only a few randomized controlled trials have compared newer OCs in a head-to-head manner, and because pregnancy rates with today's OCs are so low that demonstrating a significant difference in efficacy would require very large sample sizes. The combined daily administration of DRSP and estradiol valerate has been reported to reduce most of the frequent climacteric symptoms and to provide a slight reduction in blood pressure, preventing fluid retention and hypertension. The unwanted effects related with DRSP are minor and not medically serious. Therefore, the follow-up rate is high in both OC and menopause treatments.


Pre-weaning performance and commercial growth curve in Dorper, Katahdin, and Romanov crossed lambs in a highland zone from central Mexico.
The aim was to evaluate the pre-weaning productive performance and growth curve of Dorper*Katahdin (DPr; n = 46), Kathadin*Kathadin (KTn; n = 204) and Romanov*Kathadin (RMv; n = 40) of commercial crossed lambs from central Mexico. We considered 1450 data from 290 crossbred lambs. The variables contemplated in this study were cross (CR), lambing type (LT), sex, birth weight (BW), weaning weight (WW), test days (TD), and daily weight gain (DWG). Correlation analysis and adjustment of growth curve were performed. Differences in CR and sex were found only in BW (p < 0.05). No differences in DWG, WW, and TD (p > 0.05) by CR and sex were found. Single lambing had the highest (p < 0.05) BW, WW, and DWG. Phenotypic correlations differ among crosses. Lambs crossed with DPr presented the highest values in parameters a and b and the lowest in c. The productive behavior of DPr, KTn, and RMv cross with KTn lambs in central Mexico is similar in the pre-weaning period; however, the growth curve and parameters that characterize it suggest that DPr lambs show a tendency to enhance productive behavior in this period.


Dissociation dynamics of asymmetric alkynyl(aryl)iodonium radicals: an ab initio DRC approach to predict the surface functionalization selectivity.
The dissociation process of neutral open-shell [4-F-(C(6)H(4))-I-C≡C-(CH(2))(4)-Cl] and [4-NO(2)-(C(6)H(4))-I-C≡C-(CH(2))(4)-Cl] asymmetric iodonium radicals was studied theoretically. Vertical electron affinities and DRC (dynamic reaction coordinate) results were obtained and compared with experimental evidence. In particular, the fluorine and nitro substituent groups were selected because of (i) their opposite electron-withdrawing/electron-donating effects and (ii) experimental evidence that the grafting ability, in terms of alkynyl/aryl grafting ratio, increases with decreasing electron-withdrawing nature of the para-position substituent on the phenyl ring. DRC results show that the dissociation dynamics of the iodine-alkynyl carbon bond, for the nitro-substituted iodonium, occurs on a longer time scale than that of the fluorine-substituted iodonium. This finding is in agreement with the overall experimental results.


2,2'-Oxybis[1,3-bis-(4-meth-oxy-phen-yl)-2,3-di-hydro-1H-benzo[d][1,3,2]di-aza-borole].
In the title compound, C40H36B2N4O5, the B-O-B bond angle is 132.75 (13) and the dihedral angle between the benzodiazborole rings is 73.02 (5)°. In the crystal, weak C-H⋯O inter-actions link the mol-ecules.


Symptoms at one year following concussion from minor head injuries.
Of 131 patients with mild concussion, 19 (14.5%) still had symptoms after 1 year. Of these 19 patients, 10 had some symptoms of which they had not complained at 6 weeks. Symptoms at 1 year were more common among women and among patients who had had positive neurological findings at 24 h. Of the 19 patients who had symptoms at 1 year, 8 were involved in law suits and 6 had been suspected of malingering 6 weeks after their accident. Five of these patients were both involved in law suits and suspected of malingering.


[Cytogenetic study of cell sub-populations in human leukemias (AML, CML) sorted by flow cytometry].
Multivariate analysis, flow cytometry and sorting were used to distinguish and enrich subpopulations of bone marrow cells in cases of acute myeloblastic leukemia and blast crisis of chronic myelocytic leukemia: blast cells with a high rate of S/G2-M phase of the cell cycle; non-blast cells or blasts with a low rate of S/G2-M. These populations were separated on the basis of their forward angle and large angle light scatter of the laser beam, and of their Hoechst 33342 fluorescence intensity. About one million cells of each population were sorted and sorting purity was controlled by cytometry and microscope examination. Cell viability was good. Karyotypes of sorted cell populations were carried out using a cell synchronisation technique and showed different chromosomal markers.


Education and Executive Function Mediate Engagement in Advance Care Planning in Early Cognitive Impairment.
Advance care planning (ACP) is an important component to holistic care for people with early cognitive impairment (ECI) who are generally still mentally capable of making rational decisions. This study explores the willingness of people with ECI to engage in ACP and how clinical and behavioral variables shape their decisions. Ninety-eight persons with ECI (mild cognitive impairment or early dementia, Clinical Dementia Rating = 0.5/1.0) and assessed to have adequate insight (Clinical Insight Rating Scale) underwent an ACP information session. They were assessed on their knowledge of dementia (Knowledge of Alzheimer Disease) and willingness to engage in ACP, and were interviewed on their beliefs and attitudes toward ACP (Perceived Barriers and Benefits Scale to ACP). Univariate analysis and logistic regression identified factors that predicted persons willing or unwilling to engage in ACP based on their responses to the perceived barriers and benefits of ACP as well as sociodemographic and clinical variables. Fifty-two persons (54%) were keen on ACP. On univariate analysis, persons with better executive function [Frontal Assessment Battery (FAB)] (t = -3.63, P < .0001), were more educated (t = -2.11, P = .038) and had lower barriers to ACP (t = 2.47, P = .015), particularly less "passive coping" (t = 2.83, P = .006), were more keen on ACP. Logistic regression revealed that the combined predictive model comprising FAB, education, and passive coping as a whole reliably differentiated those unwilling to engage in ACP from those who were willing (χ(2) = 18.995, P = .001 with df = 4). Wald criterion showed that FAB (P = .016) and passive coping (P = .023) contributed most to prediction. Better education and executive function predict willingness to engage in ACP, and these factors are instrumental in a person's ability to acquire knowledge and process information. Initiating ACP discussions early, increasing efforts at education, and providing tailored information are important interventions that facilitate completion of ACP.


The Am Gene Controlling Resistance to Alfalfa mosaic virus in Tomato Is Located in the Cluster of Dominant Resistance Genes on Chromosome 6.
ABSTRACT The dominant gene Am from Lycopersicon hirsutum f. sp. glabratum PI134417 confers resistance to most strains of Alfalfa mosaic virus, including the recently identified necrotic strains. The phenotypic response includes a lack of symptom development following mechanical inoculation of leaves. To study the resistance mechanism controlled by Am, biological (back-inoculation to susceptible hosts), serological (double-antibody sandwich, enzyme-linked immunosorbent assay), and molecular (reverse transcription-polymerase chain reaction and hybridization with specific riboprobes) methods of virus detection have been conducted on mechanically inoculated PI134417 leaves. The virus was never recovered, indicating that Am acts by an inhibition of viral accumulation during the early events of the virus life cycle. Am has been mapped genetically to the short arm of tomato chromosome 6 in the resistance hotspot, which includes the R-genes Mi and Cf-2/Cf-5 and the quantitative resistance factors Ty-1, Ol-1, and Bw-5.


Special Issue: Microorganisms and Plant Nutrition.
Plant-beneficial microorganisms affect plant nutrition and health, as a key part of prebiotic-, probiotic-, and symbiotic-based interactions [...].


High frequency of endothelial vasomotor dysfunction after acute coronary syndromes in non-culprit and angiographically normal coronary arteries: a reversible phenomenon.
This study aimed to assess endothelium-dependent vasomotor function in non-culprit coronary vessels in patients with recent acute coronary syndrome (ACS). Endothelial dysfunction can also concern peripheral vessels during ACS, but the frequency of this phenomenon at coronary circulation level is unknown. Endothelial function was assessed by infusion of graded doses of acetylcholine (ACh) in a non-culprit coronary artery of normal appearance in 43 patients having recently suffered from non-ST ACS, and reassessed 6 months later. Endothelium-dependent vasoreactivity was impaired at baseline in 81% (35/43) of the patients, and only 19% (8/43) of patients showed a normal response to ACh. Among the 35 subjects with initial dysfunction, 77% showed a significant improvement 6 months later. All patients without initial endothelial dysfunction remained normal. C-reactive protein (CRP) level was elevated at month 0, and had declined at follow-up, tending towards normal levels. At that time, apolipoprotein A-I (apoA-I) levels were correlated with vasomotor improvement in univariate (p < 0.02) and multivariate analysis (p < 0.04). In conclusion, endothelium dysfunction is very frequently observed after recent ACS in non-culprit and angiographically normal coronary arteries, and an improvement occurs within 6 months in most cases. After resolution of the initial inflammation, apoA-I seems to play an important role in endothelial function.


Low calcium and calcium antagonists potentiate the contraction of guinea-pig vas deferens induced by ATP: a permissive role for P2-purinoceptors.
ATP, noradrenaline and KCl induced contractions of the isolated guinea-pig vas deferens. The ATP-induced contraction was potentiated by decreasing the external calcium concentration and was reduced by increasing the external calcium concentration. The maximum potentiation was obtained at a low calcium concentration (0.8 mM), the dose-response curve for ATP was shifted to the left in a parallel fashion at this concentration. Calcium antagonists, such as verapamil and diltiazem and MnCl2, induced a similar potentiation. On the other hand, the noradrenaline- and KCl-induced contractions were reduced by calcium antagonists and by decreasing the external calcium concentration. The ATP- and KCl-induced contractions were slightly potentiated by the removal of Mg ions from the medium, but the contractile response to ATP was not potentiated by pretreatment with difluorodinitrobenzene, an ecto-ATPase inhibitor. These results suggest that the affinity of P2-purinoceptors for ATP may be regulated by calcium sites to which calcium and calcium antagonists can bind.


Exostosis of the internal auditory canal.
Although exostoses of the external auditory canal are not uncommon, those of the internal canal are extremely rare. One of these is described occurring in a 53-year-old man whose rapidly progressive hearing loss was without any associated abnormality.


Chronic brain ischemia induces the expression of glial glutamate transporter EAAT2 in subcortical white matter.
Glutamate plays a central role in brain physiology and pathology. The involvement of excitatory amino acid transporters (EAATs) in neurodegenerative disorders including acute stroke has been widely studied, but little is known about the role of glial glutamate transporters in white matter injury after chronic cerebral hypoperfusion. The present study evaluated the expression of glial (EAAT1 and EAAT2) and neuronal (EAAT3) glutamate transporters in subcortical white matter and cortex, before and 3-28 days after the ligation of bilateral common carotid arteries (LBCCA) in rat brain. K-B staining showed a gradual increase of demyelination in white matter after ischemia, while there was no cortical involvement. Between 3 and 7 days after LBCCA, a significant increase in EAAT2 protein levels was observed in the ischemic brain and the number of EAAT2-positive cells also significantly increased both in the cortical and white matter lesions. EAAT2 was detected in glial-fibrillary acidic protein (GFAP)-positive astrocytes in both the cortex and white matter, but not in neuronal and oligodendroglial cells. EAAT1 was slightly elevated after ischemia only in the white matter, but EAAT3 was at almost similar levels both in the cortex and white matter after ischemia. A significant increase in EAAT2 expression level was also noted in the deep white matter of chronic human ischemic brain tissue compared to the control group. Our findings suggest important roles for up-regulated EAAT2 in chronic brain ischemia especially in the regulation of high-affinity of extracellular glutamate and minimization of white matter damage.


A rare case of left dominant pulmonary edema in acute mitral regurgitation.
Unilateral pulmonary edema (UPE) due to cardiac causes is an unusual clinical finding and typically emerges on the right side. UPE poses a diagnostic challenge due to difficulty distinguishing infiltrative pneumonia from cardiogenic edema on chest imaging. Consequently, corrective clinical management is significantly delayed in UPE compared to bilateral cardiogenic pulmonary edema. We present a very rare case of left-sided cardiogenic pulmonary edema due to acute severe MR wherein a prompt cardiac evaluation for UPE led to successful corrective surgery and favorable outcome.


A collaborative escape room as gamification strategy to increase learning motivation and develop curricular skills of occupational therapy students.
This study presents an experiment regarding the introduction of gamification strategies in occupational therapy courses. Based on previous studies, the objective is to adapt the idea of recreational escape rooms to educational environments of health sciences like occupational therapy to increase student motivation and promote game-based learning and key skills, such as teamwork. Computer software was created for a collaborative escape room which allows on-line simultaneous play of up to 24-30 students. It was tested three times in an occupational therapy degree program with 75 students and it was based on two different subjects, although it can be adapted to others. The escape room was evaluated using feedback surveys and comparing students' performances before and after the game. Descriptive exploratory statistical analysis was performed using SPSS version 24. An appropriate use of educational escape rooms can have significant positive impacts on students' engagement and learning. Students were found to prefer using gamification tools in their learning. Their degrees of satisfaction exceeded their expectations. Educational escape rooms may have a positive impact on students' motivation and a statistically significant improvement of test scores after playing was found. Comments from the feedback surveys were used to improve successive versions of the software and design of the game. T.F.G. n° 2020.038 (Research Ethics Committee of the Principality of Asturias).


Comparison of anterior surgical options for the treatment of multilevel cervical spondylotic myelopathy: a systematic review.
Systematic review. The primary objectives of this review were to compare the effectiveness and safety of various anterior cervical decompressive and reconstructive procedures for diffuse or multifocal cervical spondylotic myelopathy (CSM). An additional objective was to describe the most common ancillary stabilization techniques used with the different anterior decompressive procedures. Surgical management of CSM provides for neurological recovery and disease stabilization in a cost-effective way. Although both retrospective and prospective data support management of CSM by anterior cervical decompression and fusion, the choice decision between various anterior surgical options remains unclear. We conducted a systematic search in MEDLINE and the Cochrane Collaboration Library for human studies in the English-language literature published through September 2012. We included studies comparing multiple discectomies with single or multiple corpectomy, multiple discectomies with discectomy-corpectomy hybrid, and multiple corpectomies with discectomy-corpectomy hybrid, comparing effectiveness and safety outcomes of each procedure, and defining the ancillary stabilization techniques used. Exclusion criteria included patients with degenerative disc disease or degenerative joint disease without CSM, single-level CSM, ossified posterior longitudinal ligament (OPLL), spinal tumor, concomitant infection, and ankylozing spondylitis. Case series, case reports, data not reported separately for each comparison group, or studies that consisted of an N less than 10 for either comparison group were excluded. The evidence strength was rated using the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) criteria. Of the 49 citations identified from our search, 10 studies were initially found suitable for inclusion. Patients undergoing any of the 3 procedures generally experienced improvements in clinical outcomes (neck disability index, Japanese Orthopaedic Association score, and Visual Analogue Scale score for pain) as well as overall sagittal alignment, with minimal perioperative morbidity. There is moderate evidence supporting selection of multiple discectomies compared with corpectomy or discectomy-corpectomy hybrid procedures with regard to superior clinical outcomes and postoperative sagittal alignment. Furthermore, if more extensive operation is needed, there is evidence to support the selection of discectomy-corpectomy hybrid procedures compared with multiple corpectomies if it is technically feasible to accomplish the requisite decompression. The multiple discectomies approach also may have a lower incidence of C5 palsy than corpectomy or discectomy-corpectomy hybrid approaches. All 3 operative approaches are effective strategies for the anterior surgical management of CSM. When the patient pathoanatomy permits, selection of multiple discectomies is favored compared with corpectomy or discectomy-corpectomy hybrid approaches. EVIDENCE-BASED CLINICAL RECOMMENDATIONS: When pathoanatomically appropriate with minimal retrovertebral disease, we recommend the selection of multiple discectomy over corpectomy or discectomy-corpectomy hybrid procedures. Low. Strong. When retrovertebral disease is significant, we recommend, when possible, that discectomy-corpectomy hybrid procedures be performed instead of multiple corpectomies. Moderate. Strong. SUMMARY STATEMENTS: There is no evidence to guide choice of ancillary external immobilization techniques following multilevel anterior decompression and fusion procedures for CSM.


Superhelical DNA with local substructures. A generalization of the topological constraint in terms of the intersection number and the ladder-like correspondence surface.
The presence of certain local structural elements in superhelical DNA, such as cruciforms and denatured loops, complicates the topological and geometric analysis of these molecules. In particular, the duplex axis is often difficult to define. In consequence, the usual conservation condition, Lk = Tw + Wr, is often inapplicable as formulated in terms of the winding of either strand of the DNA about the duplex axis. We present here a more general formulation of the topological conservation condition in terms of a model in which the two strands of DNA are regarded as twisting about one another, and in which one of the two strands is considered to writhe. We define a ladder-like correspondence surface, which connects the two strands nd is independent of whether or not a unique duplex axis is locally available. These considerations lead to the definition of a new topological property of superhelical DNA, the intersection number, In. This quantity describes the complexity of a local structural element; in the case of a cruciform, for example, the intersection number is a measure of the number of duplex turns removed from the major segment of the DNA by the cruciform formation. In more general terms, the topological constraint applicable to closed circular DNA is given by Lk(W,C) + In(S,C) = Tw(W,C) + Wr (C), where W and C represent the two strands of the DNA and S is the ladder-like correspondence surface that connects the two strands.


Augmentation of the human monocyte/macrophage chemiluminescence response during short-term exposure to interferon-gamma and tumour necrosis factor-alpha.
The effects of short-term (30 min) pre-incubation of human monocytes and macrophages (3-day cultured monocytes) with leucocyte-derived human interferon-gamma (IFN-gamma) and recombinant human tumour necrosis factor-alpha (rTNF-alpha) were examined. Pre-incubation of either monocytes or macrophages with rTNF-alpha or IFN-gamma (100 U/5 x 10(5) cells) augmented their respiratory burst to formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), measured by the luminol- and lucigenin-dependent chemiluminescence assay. In addition, both cell types showed a burst of respiratory activity in the presence of rTNF-alpha or IFN-gamma only. The effects of IFN-gamma were removed by adsorption with an anti-IFN-gamma monoclonal antibody and those of rTNF-alpha were abolished by heating at 100 degrees C, or by the addition of anti-TNF-alpha monoclonal antibody. The results demonstrate that both IFN-gamma and rTNF-alpha are stimulators of monocytes and macrophages, and rapidly alter the capacity of the cells to respond to fMLP, which binds to cell surface receptors.


Using Patient-Level Data to Develop Meaningful Cross-Trial Comparisons of Visual Impairment in Individuals with Diabetic Macular Edema.
The aim of this study was to assess the impact of baseline characteristics on visual outcome of patients with diabetic macular edema and compare the results of clinical trials with different patient populations. A model was created with patient-level data from the RESPOND/RESTORE trials to estimate the impact of baseline characteristics on increases in best-corrected visual acuity (BCVA) with anti-vascular endothelial growth factor therapies, measured by letters gained on the Early Treatment Diabetic Retinopathy Study scale from baseline to month 12. Mean BCVA gains with ranibizumab 0.5 mg pro re nata or laser photocoagulation monotherapy were predicted, assuming baseline characteristics equivalent to those in the VIVID-DME/VISTA-DME trials. These results were compared with the gain with aflibercept 2.0 mg every 8 weeks in VIVID-DME/VISTA-DME. Sensitivity analyses assessed outcome robustness. Baseline BCVA and central retinal thickness differed significantly between trials. In unadjusted data, patients in RESPOND/RESTORE receiving ranibizumab gained an additional 6.6 letters [95% confidence interval (CI): 4.5-8.7] compared with patients receiving laser monotherapy. After adjusting data to assume baseline characteristics equivalent to VIVID-DME/VISTA-DME, patients receiving ranibizumab were predicted to gain an additional 9.9 letters (95% CI: 7.3-12.4) compared with those receiving laser monotherapy. These results were similar (0.1-letter difference in favor of aflibercept; 95% CI: -2.9 to 3.2; P = 0.94) to the gain in BCVA in patients receiving aflibercept in VIVID-DME/VISTA-DME compared with those receiving laser monotherapy (10.0 letters, 95% CI: 8.3-11.7). After adjusting for baseline characteristics, the difference in letters gained between patients receiving ranibizumab versus aflibercept was non-significant across trials, highlighting the importance of adjusting for baseline characteristics in future comparisons. Novartis Pharma AG.


Reduced brain insulin signaling: A seminal process in Alzheimer's disease pathogenesis.
The synaptic dysfunction and death of neurons that mediate memory and cognition account together for the behavioral symptoms of Alzheimer's disease (AD). Reduced insulin signaling in the brain is a hallmark of AD patients, even in the absence of systemic type 1 or type 2 diabetes, prompting some researchers to refer to AD as brain-specific, or type 3 diabetes. A key question that arises about this signature feature of AD is "how, if at all, does the brain's impaired ability to utilize insulin contribute to the behavioral deficits associated with AD?" The fact that type 2 diabetes is a risk factor for AD suggests a causative role for impaired insulin responsiveness in AD pathogenesis, but how that might occur at a detailed molecular level had been elusive. Here we review recent findings that mechanistically link soluble forms of amyloid-β (Aβ) and tau, the respective building blocks of the amyloid plaques and neurofibrillary tangles that accumulate in the brains of AD patients, with neuronal decline that is associated with poor insulin responsiveness and may begin long before AD symptoms become evident. We discuss how Aβ and tau work coordinately to deprive neurons of functionally accessible insulin receptors and dysregulate normal signaling by the protein kinase, mTOR. Finally, we suggest how newly gained knowledge about pathogenic signaling caused by reduced brain insulin signaling might be exploited for improved early detection and therapeutic intervention for AD. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'


Psychophysiological correlates of anxiety: a single-case study.
We examined the relationship between self-reported anxiety and physiological measures (blood pressure and heart rate) in a series of exposures to a feared situation of a single participant with panic disorder with agoraphobia. During each exposure, readings of heart rate, systolic blood pressure and diastolic blood pressure were taken every 20 s. Over 30 exposures, we found a near-linear relationship between anxiety and the three physiological measures. Implications of this result for usefulness of physiological measures in anxiety research and in the clinical treatment of anxiety disorders are discussed.


Experimental strategies for modification of histocompatibility antigens in tumor cells.
Cancer may be thought of as an immunological disorder that arises because certain 'transformed' cells, endowed with the propensity to divide, have learned to evade detection by the immune system. The prospect of intervention by 'immunotherapy' depends very much on our ability to either [1] render cancer cells more recognizable to the immune system, or [2] potentiate the immune system towards a more effective recognition of cancer cells. There is now direct evidence that suppression of the major histocompatibility complex class I antigens, a family of cell-surface glycoproteins required for the presentation of cancer cells to the immune system, is directly responsible for the ability of tumor cells to escape immune surveillance. It has been shown that cancer cells can be made immunogenic either by the expression of an exogenous class I gene introduced by DNA-mediated gene transfer, or by the derepression of endogenous class I genes with interferon; these cells are efficiently rejected by the immune system. Even more interesting is the finding that the immune system can be potentiated to reject tumors by immunization with homologous tumor cells that have been manipulated to express normal levels of class I antigens. Since increasing numbers of human tumors have been found to have greatly reduced levels of class I antigens, these findings suggest a direct route to immunotherapy that involves debulking of the tumor mass, raising the level of class I antigens in a small number of explanted tumor cells, and re-immunizing the host.


Hypothetical assessment of efficiency, willingness-to-accept and willingness-to-pay for dengue vaccine and treatment: a contingent valuation survey in Bangladesh.
In 2019, Bangladesh has grappled with a record-breaking surge in dengue fever, experiencing the highest number of dengue cases since the year 2000. Together, the intensification of dengue fever combined with a lack of dengue vaccines and appropriate medicines is expected to further the public and government's interests in appropriate and potential dengue vaccines to control the epidemic. We considered people's characteristics, dengue experience, and knowledge to assess their willingness-to-accept (WTA) and willingness-to-pay (WTP) for a hypothetical dengue vaccine and ex-post treatment in Bangladesh (June-July 2019). This study implemented a contingent valuation (CV) method with 3,251 respondents in 10 different locations of Bangladesh. All respondents participated in a hypothetical dengue vaccine scenario consisting of 65% (vaccine A), 80% (vaccine B), and 95% (vaccine C) effectiveness levels with three doses of each vaccine and ex-post dengue treatment. Around 71.2% of respondents were willing to pay for at least one of the hypothetical vaccines: A, B, or C. The average WTPs of the three vaccines amounted to US$ 47.0, US$ 66.0, and US$ 89.0, which were defined as the total cost of the doses necessary to obtain immunity. In Bangladesh, there is a significant demand for low-priced dengue vaccines, which was proven by people's higher acceptance of vaccination practices. Though dengue vaccines are not yet available in Bangladesh, this study provides significant support that both the government and private sectors should work together to develop a reliable and affordable dengue vaccine.


Early responses given distinct tactics to infection of Peronophythora litchii in susceptible and resistant litchi cultivar.
Litchi downy blight, a destructive litchi disease caused by Peronophythora litchii, is controlled by intensive fungicide applying. Sources of resistance are used in conventional breeding approaches, but the mechanism is not well understood. Follow-up six years investigation, 'Guiwei' and 'Heiye' displayed stable susceptible and resistant against to P. litchii, respectively. After 72 hour inoculation, 'Heiye' showed few disease spots, while 'Guiwei' appeared brown and covered with white sporangia. Germination of sporangia and growth of mycelium in 'Guiwei' is more quickly than in 'Heiye'. Transcript levels were measured at 6, 24, and 48 hour post-inoculation. 'Oxidation-reduction process' was dramatically enhanced in 'Heiye', which could promote its resistance to pathogen infection. A small ratio (3.78%) of common DEGs indicates that resistant and susceptible cultivars take different strategies to defense against P. litchii. At early infection stage, 'Heiye' induced a larger number of genes, including seven receptor-like kinases, which quickly recognized attack of pathogen and led to a rapidly resistance by regulation of degradation of proteasome, transcription factors, and cell wall remodeling. The early DGEs were exiguous in 'Guiwei', suggesting a weak response. Once the infection was successful, the resistance was repressed by down-regulated genes involved in phenylpropanoid metabolism, ET biosynthesis and signaling conduction in 'Guiwei'. In conclusion, quickly recognition and early responses to pathogen, as well as minimal pathogen development and basal expression of resistance-related genes, were correlated with a high level of resistance in 'Heiye', while susceptible 'Guiwei' suffered massive infection due to lagging response and repressed signal transduction.


Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart.
The Na(+)/Ca(2+) exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na(+) concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 microM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na(+) concentrations in rabbit and rat hearts. The concentration-dependent effects of SEA0400 on I(Na/Ca) were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry. SEA0400 inhibited I(Na/Ca) with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 microM SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities. NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na(+) concentration may play an important role in the contractility response to NCX inhibition.


Objective age of acquisition norms for a set of 328 words in Spanish.
Age of acquisition is one of the most important variables in picture naming. For this reason, a large number of findings concerning age-of-acquisition data have been published in recent years in a number of different languages. In this article, objective age-of-acquisition data in Spanish for 328 pictures were collected from a pool of 760 children, half of whom were boys and the other half girls. A total of 246 pictures were selected from the Snodgrass and Vanderwart (1980) set, and 82 were new pictures. Like the results of other studies, we found that objective age of acquisition correlates less than rated age of acquisition with familiarity and frequency, which indicates that the objective measure is less contaminated by other variables than are rated estimates. A very high correlation was obtained between the norms from this study and those published in English, French, Icelandic, and Italian. These norms will be very useful to Spanish psycholinguists and clinicians. Related materials may be downloaded from the Psychonomic Society Web archive at www.psychonomic.org/archive/.


A potent dipeptide inhibitor of dipeptidyl peptidase IV.
A series of novel potent inhibitors of dipeptidyl peptidase IV (DPP-IV) has been developed. A brief structure-activity relationship of the inhibitors was investigated. The dipeptide TSL-225, tryptophyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, was identified with the critical structure for the inhibitory activity.


[Changes in risk factors for spontaneous abortion in an area with high concentrations of shoe manufacture after a preventive intervention].
Risk factors of spontaneous abortion were investigated in two matched case-control studies in 1987-88 and 1997-99. An history of previous abortions significantly increased the risk in both studies. Lifestyle (coffee) and occupational (exposure to organic solvents) factors were associated with a significantly increased risk in the first but not in the second calendar period, following a community intervention with advice given to workers, employers, and physicians; the latter also counseled a greater use of medicines against spontaneous abortion.


Social learning and the adaptiveness of expressing and perceiving fearfulness.
The fearful ape hypothesis revolves around our ability to express and perceive fearfulness. Here, we address these abilities from a social learning perspective which casts fearfulness in a slightly different light. Our commentary argues that any theory that characterizes a (human) social signal as being adaptive, needs to address the role of social learning as an alternative candidate explanation.


Laser-assisted microdissection of membrane-mounted sections following immunohistochemistry and in situ hybridization.
Laser microbeam microdissection (LMM) is an increasingly important histological technique for obtaining homogeneous cell populations and tissue components in order to analyze target-specific changes in genes, gene expression, and proteins. The quality of data obtained with LMM is heavily dependent on the precision with which the target for microdissection can be identified. Since no cover slip is used during LMM, tissue morphology is poor compared with traditional light microscopy. This hampers morphological recognition of targets for microdissection in routinely stained sections and can be a limiting factor in the use of this technique. Immunohistochemistry (IHC) and in situ hybridization (ISH) can improve the identification of specific cell populations in situ in tissue sections, but there are a number of problems in applying these methods to slides prepared for LMM. In this chapter, we present optimized protocols that allow IHC to be performed for detecting a wide range of antigens in conjunction with LMM, both on formalin-fixed paraffin-embedded and on frozen sections. In addition, we present a quick, versatile protocol for performing ISH on archival material suitable for LMM.


Decreased endometrial HOXA10 expression associated with use of the copper intrauterine device.
To characterize human endometrial HOXA10 expression in patients using a copper intrauterine device (IUD). Case-control study. Academic medical center. Women using copper IUDs. Immunohistochemical analysis of endometrial HOXA10 expression in biopsy samples obtained from 24 women using a copper Paraguard T380A as well as in samples obtained from 10 normal cycling women who were not using an IUD or hormonal contraceptives. Endometrial HOXA10 expression. Endometrial HOXA10 expression was markedly decreased in the biopsy samples obtained from women using the IUD contraceptive when compared with controls. The mean H score for endometrial stromal cell HOXA10 expression in samples obtained from women using the Paraguard IUD was 0.21 compared with 2.2 in the control endometrial biopsy samples. Endometrial glandular expression of HOXA10 was absent in all IUD users. Decreased endometrial HOXA10 expression was apparent in women who use a copper IUD. Expression of HOXA10 is essential for endometrial receptivity. A novel mechanism of copper IUD action involves suppression of genes required for endometrial receptivity. The dramatic decrease of endometrial HOXA10 in response to IUD use may contribute to contraceptive efficacy.


Gender affirming surgery in non-binary patients: The importance of patient-centered care.
Gender-affirming mastectomies are a growing necessity for transgender and gender-diverse patients. The preoperative evaluation and surgical outcome must be tailored to the individual, taking into consideration previous medical history, medications, hormonal therapy, patient anatomy, and expectations. Although non-binary patients constitute a significant portion of patients referring for gender-affirming mastectomies, current literature rarely acknowledges them as a separate patient category from trans-masculine patients. Retrospective cohort, demonstrating the single-surgeon experience with gender-affirming mastectomies over the course of 2 decades. A total of 208 patients were included in this cohort, patients identifying as "non-binary" in gender accounted for 30.8% of the cohort. Non-binary patients were found to be younger (P value<0.001) at the time of surgery, at the time of HRT initiation (P value<0.001), at the first feeling of gender dysphoria, coming out to society, and use of non-female pronouns (P value = 0.04,<0.001 and<0.001, accordingly). In the non-binary patient group, a shorter period of time passed from the first feeling of gender dysphoria to initiation of HRT and surgery (P value<0.001 and<0.001, accordingly). However, the average time from HRT initiation to surgery and from the first use of non-female pronouns to HRT initiation or surgery did not statistically differ (P value= 0.34, 0.06, and 0.08, accordingly). Non-binary patients demonstrate a significantly different timeline from trans-masculine patients in terms of gender development. In order to accommodate their needs, caregivers must take the information into consideration and develop appropriate guidelines and courses of action.


Implementing open educational resources in digital education.
The outbreak of COVID-19 leads to an increasing demand for online educational resources to continue teaching and learning. Open educational resources (OER), with the benefits of cost-saving and open licenses, have great potential in facilitating the rapid transition to digital education, but concerns about whether OER decrease the effectiveness of student learning remains unsolved. Hilton's review article (2016) provides synthesized evidence stating that OER can help decrease college students' textbook spending without undermining student learning effectiveness. It is also noteworthy that implementing OER in digital education needs additional considerations beyond the efficacy of OER. Therefore, this special issue article extends Hilton's (2016) synthesized findings by presenting four additional perspectives in research, design, culture, practice about implementing OER in digital education.


Histopathology of nasopharyngeal carcinoma: correlations with epidemiology, survival rates and other biological characteristics.
A total of 363 cases of nasopharyngeal carcinoma (NPC) in Singapore were classified into squamous cell carcinoma (SCC; 73 cases), non-keratinizing carcinoma (NKC; 178 cases) and undifferentiated carcinoma (UC; 172 cases). Possible biological differences between these histologic types and between tumors with and without lymphocytic infiltration were investigated by correlations with survival rates and with selected epidemiologic, immunovirologic, and immunogenetic data on the disease. The 5-year survival rates following radiotherapy were 25.3% for all cases and 58.8% for tumors restricted to the nasopharynx. The 5-year survival rate for SCC was poorer than for the combined NKC and UC groups (p less than 0.05). The 3-year survival rate was better for tumors with lymphocytic infiltration (p less than 0.05), but there were no differences in the 5-year survivals. The survival rates were better in females (p less than 0.01) and in the younger age groups (p less than 0.01). There were no significant correlations between histopathology of NPC and the distributions of cases by age, sex, HLA antigen profiles, or cell-mediated immune status. Squamous cell carcinoma was associated with lower levels of antibodies to the Epstein-Barr nuclear antigen (p less than 0.05), but there were no differences with respect to antibodies against other EBV related antigens. These findings support the view that SCC, NKC, and UC of the nasopharynx, as defined in the WHO classification, are variants of a fairly homogeneous group of neoplasms in the Singapore population.


The history of awake craniotomy for brain tumor and its spread into Asia.
In ancient times, awake craniotomy was used for trepanation to treat seizures and remove a variety of morbid conditions or even to permit the escape of evil air. In modern times, this technique was initially used for removal of epileptic foci with simultaneous application of brain mapping with electrical current. Further developments brought this technique into use for resection of tumors involving functional cortex. Recently, awake craniotomy has been described as an approach for removal of supratentorial tumors nonselectively, regardless of the involvement of eloquent cortex. It has been used in North America since the 1980s, then Europe, and recently has spread into Asia. Its spread to Asia could have significant impact based on the large population of patients and the low resource utilization associated with awake craniotomy.


Platelet counting in platelet concentrates with various automated hematology analyzers.
Hematology analyzers use impedance, optical, and/or immunologic techniques for counting platelets (PLTs). PLT counting in whole blood has been validated thoroughly; however, this is not the case for PLT counting in PLT concentrates (PCs), in which red cells (RBCs) are absent. Therefore, this study is focused on PLT counting in PCs to study use of ethylenediaminetetraacetate (EDTA), carryover, and accuracy of the analyzers. In total six hematology analyzers (AcT 8, Beckman Coulter; ADVIA 2,120, Bayer; Cell-Dyn 4,000, Abbott; Onyx, Beckman Coulter; K4,500, Sysmex; and XT 2,000i, Sysmex) were tested for PLT counting. PC samples with various PLT concentrations were made (0-1,700 x 10(9)/L) and measured 10 times. Carryover was determined five times. PC samples (1,000 x 10(9) PLTs/L) in EDTA tubes showed significantly higher PLT counts than samples in "dry" tubes for all analyzers except for the Cell-Dyn 4,000 with the impedance technique. Carryover was not more than 0.3 percent for all analyzers. The K4,500 showed the most accurate results, whereas the Cell-Dyn 4,000 with the impedance technique had low accuracy due to an overestimation of more than 20 percent. Most tested analyzers seemed to be suitable for counting PLTs in PCs. All hematology analyzers should be validated for counting PLTs in absence of RBCs as is the case in PCs, in addition to validation of PLT counting in whole blood.


Isolation and culture of rat cone photoreceptor cells.
In retinal diseases characterized by photoreceptor degeneration, the main cause of clinically significant vision loss is cone, rather than rod, loss. Photoreceptor apoptosis can be affected by the availability and/or delivery of neurotrophic proteins, and cultures of photoreceptors are valuable for studying these processes. In the present study, a technique was designed to purify cones to make it possible to screen for neuroprotective molecules. The present chapter describes a technique for preparing cultures of purified rat retina cone photoreceptors based upon panning with peanut agglutinin lectin, which selectively binds to cones. In addition, we describe a protocol for the purification and culture of retinal pigmented epithelial cells from postnatal rat.


Age-specific angulation of unerupted human third molar teeth in a cross-sectional sample.
For males aged 18 to 21, the angulation of unerupted third molars was unrelated to age. A counterbalancing loss of data resulting from tooth eruption and extraction accounted for this null finding. The value of age-specific angulation in determining whether a tooth will eventually erupt may be limited.


Changes in the activity of 'active' pyruvate dehydrogenase complex in the newborn of normal and diabetic rats.
At birth, hepatic 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities in the newborn of normal, mildly diabetic, and severely diabetic rats were similar. The 'active' and 'dichloracetate-activated' pyruvate dehydrogenase complex activities increased significantly during the first 2 and 6 postnatal h, respectively in the three groups of neonates (p less than 0.05). The greatest increase in both 'active' and 'dichloroacetate-activated' pyruvate dehydrogenase complex activity was observed in the neonates of mildly diabetic rats. Administration of glucose or insulin at birth to the newborn of normal rats caused a significant increase in the percentage of 'active' pyruvate dehydrogenase complex activity within 1 h (p less than 0.01). Similar treatment caused no significant increases in the newborn of severely diabetic rats. The transient increases in 'active' pyruvate dehydrogenase complex activity in the neonates of normal and diabetic rats were consistent with rapid disappearance of blood lactate during the first hours of postnatal life.


Ultrasound-Guided Perineural Injection at Guyon's Tunnel: An Anatomic Feasibility Study.
Compression of the ulnar nerve (UN) at the wrist causes neuropathy in the ulnar tunnel (UT), or Guyon's tunnel. In the absence of trauma and motor syndromes, primarily conservative treatment is considered. As in carpal tunnel syndrome, a perineural injection of corticosteroids may be beneficial. The aim of this study was to investigate the feasibility of ultrasound-guided injections at the UT. We performed ultrasound-guided injections of ink at the UN within the UT in 21 limbs from 11 non-embalmed cadavers. In all cases, we stained the perineural sheath of the superficial branch of the ulnar nerve within the UT. No ink was found inside the nerve or in adjacent structures such as blood vessels and tendons. In conclusion, perineural injection of the UN in the UT seems to be a technically feasible procedure. On the basis of these anatomic data, clinical trials are needed to prove the concept for routine use.


Factors associated with herd restriction and de-restriction with bovine tuberculosis in British cattle herds.
The incidence of herd breakdown (HBD) with bovine tuberculosis (bTB) has continued to increase year on year since the 1980s in Great Britain. The management of bTB constitutes a major challenge for government and the cattle industry. Whilst various factors have been implicated with the risk of HBD with bTB, factors involved in recovery are less well described. In this paper, we used a multilevel multistate model to identify the factors affecting the probability of a herd being placed under restriction following a bTB outbreak and the factors involved in those restrictions being lifted. By modelling both transitions within the same model, we control for unobserved herd-specific characteristics, and investigate the frequency of change between the restricted and derestricted states. There were two patterns of herd breakdown: transient (characterised by fast cycling between restricted and derestricted states) and continuous (characterised by rare changes between the two states). The risk of a herd being placed under restriction was dominated by predictors related to cattle movements. The probability of derestriction increased with more regular testing. Some risks affected both transitions, namely loge mean size of neighbouring herds in the test-year, whether the herd bred its own replacements and the foot and mouth disease indicator of whether a bTB test was done between February 2002 and January 2003, possibly because the underlying true state of the herd, as infected or not, meant that these factors increased or reduced the risk of HBD. These results highlight that management of bTB is dependent on the true underlying herd status of bTB infection and that some confusion of the benefits or otherwise of some management practices, e.g. using home bred replacements can be explained by this underlying status.


The impact of maternal depression on child mental health treatment and models for integrating care: a systematic review.
Maternal depression negatively impacts child mental health and is a well-known risk factor for child psychopathology. However, maternal depression treatment and child mental health treatment are rarely integrated. The purpose of this review was to assess the impact of maternal depression on child mental health treatment, including (1) how treatment of maternal depression affects child mental health outcomes, (2) the impact of maternal depression on children receiving mental health care, and (3) emerging models that address maternal depression in primary-care pediatrics and child mental health settings. A systematic literature review was conducted using PubMed and PsycInfo. Initial search yielded 224 records, and after exclusion, 29 papers were reviewed. Effective treatment of maternal depression is associated with a significant decrease in child psychiatric symptoms. Maternal depression negatively affects child mental health treatment in that there is a high rate of untreated mental illness among mothers of psychiatrically ill children, and maternal depression impedes effective child mental health treatment. Current models to address maternal depression in child settings include screening in pediatric primary care, psychotherapy for depressed mothers of psychiatrically ill children, and emerging models that integrate maternal and child mental health treatment. Effective treatment of maternal depression significantly improves child mental health and should be better integrated into child treatment. Opportunities to improve care include more robust screening for parental mental illness, supports to refer parents to psychiatric care, and on-site services for parents. Such interventions hold promise, but require significant support from a multidisciplinary team.


Combined techniques for double valve replacement in the infant.
A 6-month-old female infant was seen with heart failure secondary to severe aortic and mitral regurgitation. As a neonate the infant had undergone an aortic valvotomy for congenital aortic stenosis. Subsequently the infant had aortic and mitral regurgitation with an infarcted papillary muscle. Double valve replacement was carried out with the St. Jude valve. The first approach was by the Manouguian procedure with extension of the aortotomy out between the left coronary cusp and the noncoronary cusp. The posterior mitral apparatus was resected, and a 19-mm St. Jude aortic valve was sewn into the mitral position. Because the enlarged aortic valve annulus was still inadequate to accommodate a 19-mm St. Jude valve, a Konno procedure was carried out to enlarge the aortic ring anteriorly. Atrial, septal, and aortic repair and right ventricular outflow tract reconstruction were carried out with bovine pericardium. Bypass was carried out with standard techniques of hypothermia, aortic cross-clamping, and cardioplegia. Postoperative anticoagulation therapy was initially with aspirin and dipyridamole (Persantine); however, clotting of the mitral prosthesis necessitated treatment with urokinase and heparin, which completely resolved the clot. Sodium warfarin (Coumadin) therapy was then begun. One year postoperatively, the child is developing normally.


Coronary microvascular function in early chronic kidney disease.
coronary microvascular dysfunction may underlie the high cardiovascular risk associated with chronic kidney disease (CKD), but the effects of CKD on coronary microvasculature function remain uncertain. we assessed myocardial blood flow changes in mild-to-moderate CKD and analyzed the association between creatinine clearance (CrCl) and peak myocardial blood flow and coronary flow reserve (CFR) measured as the ratio of stress to rest perfusion at baseline and at 1 year in 435 nondiabetic individuals who underwent quantitative rest and pharmacological stress positron emission tomography imaging. At baseline, CFR was significantly associated with CrCl (β per 10 mL/min increase, 0.07; P=0.001). Factors such as age and blood pressure accounted for this association, and it was not significant in adjusted analyses (β=-0.02, P=0.53). Peak flow was not associated with CrCl in either crude or adjusted analyses (β per 10 mL/min=-0.02 mL/min per g, P=0.29). Although change in peak flow at 1 year was similar in patients with and without CKD, CrCl was a strong and independent predictor of a higher rate of change in CFR, with a loss of 0.11 CFR units/y (95% confidence interval, 0.01 to 0.20) for each 10 mL/min drop in CrCl (P=0.03). these findings demonstrate that mild-to-moderate CKD is not independently associated with a reduction in peak myocardial flow or CFR and suggests that microvascular changes are unlikely to explain the high cardiovascular mortality in mild to moderate CKD. Loss of CFR, however, may accelerate in mild to moderate CKD. Further studies are needed to determine whether these changes lead to more significant reductions that may reduce peak flows and CFR and contribute to cardiovascular risk in more severe CKD.


RHPN1-AS1 Drives the Progression of Hepatocellular Carcinoma via Regulating miR-596/IGF2BP2 Axis.
Hepatocellular carcinoma (HCC) is one of the most deadly cancer types worldwide, and its incidence is high in China. Multiple long non-coding RNAs (lncRNAs) have been recently identified as crucial oncogenic factors or tumor suppressors. In this study, we explored the effects of LncRNA RHPN1 antisense RNA 1 (RHPN1-AS1) on the progression of HCC. Expression levels of RHPN1-AS1 and miR-596 in HCC samples were measured by qRT-PCR. The association between pathological indexes and the expression level of RHPN1-AS1 was also analyzed. Human HCC cell lines Huh7 and SMMC-7721 were used as cell models. CCK-8 and colony formation assays were performed to assess the effect of RHPN1-AS1 on HCC cell line proliferation. The flow cytometer instrument was used to study the effect of RHPN1-AS1 on apoptosis of HCC cells. The transwell assay was conducted to detect the effect of RHPN1-AS1 on migration and invasion. Furthermore, luciferase reporter assay was used to confirm targeting of miR-596 by RHPN1-AS1. Additionally, the regulatory function of RHPN1-AS1 on insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) was detected by western blot. The expression level of RHPN1-AS1 in HCC samples was observed to significantly increase compared with normal tissues and its high expression was correlated with unfavorable pathological indexes. Highly expressed RHPN1-AS1 was associated with shorter overall survival time. RHPN1-AS1 overexpression remarkably accelerated proliferation and metastasis of HCC cells, while reduced apoptosis. Accordingly, RHPN1-AS1 knockdown suppressed the malignant phenotypes of HCC cells. RHPN1-AS1 overexpression significantly reduced miR-596 expression by sponging it, but enhanced IGF2BP2 expression. RHPN1-AS1 acts as a sponge of tumor suppressor miR-596 in HCC that can indirectly enhance the IGF2BP2 expression and function as an oncogenic lncRNA.


Serum total lipids, lipoproteins cholesterol, apoproteins A and B in cardiovascular disease.
Serum total lipids and lipoproteins cholesterol were determined in 33 survivors of myocardial infarction (MI) and in 75 subjects with peripheral vascular disease (PVD). Measurements were also made by a quantitative immunological assay of Apoprotein A (Apo A) and B (Apo B). Apo A levels were significantly lower in cases than in controls. In those cases with low levels of Apo A, high density lipoprotein has a higher cholesterol content as compared with controls. A negative correlation between high density lipoprotein cholesterol and low density lipoprotein cholesterol was found in controls and PVD subjects. The findings suggest that Apo A is associated to MI and PVD and its quantitative determination is predictive of cardiovascular disease.


Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3β-C/EBPβ pathway.
Del-1 is an endothelial cell-secreted anti-inflammatory protein. In humans and mice, Del-1 expression is inversely related to that of IL-17, which inhibits Del-1 through hitherto unidentified mechanism(s). Here we show that IL-17 downregulates human endothelial cell expression of Del-1 by targeting a critical transcription factor, C/EBPβ. Specifically, IL-17 causes GSK-3β-dependent phosphorylation of C/EBPβ, which is associated with diminished C/EBPβ binding to the Del-1 promoter and suppressed Del-1 expression. This inhibitory action of IL-17 can be reversed at the GSK-3β level by PI3K/Akt signalling induced by D-resolvins. The biological relevance of this regulatory network is confirmed in a mouse model of inflammatory periodontitis. Intriguingly, resolvin-D1 (RvD1) confers protection against IL-17-driven periodontal bone loss in a Del-1-dependent manner, indicating an RvD1-Del-1 axis against IL-17-induced pathological inflammation. The dissection of signalling pathways regulating Del-1 expression provides potential targets to treat inflammatory diseases associated with diminished Del-1 expression, such as periodontitis and multiple sclerosis.


Acquired atrioesophageal fistula: Need it be lethal? Sizing up the problem, diagnostic modalities, and best management.
An atrioesophageal fistula is a devastating complication of ablation for atrial fibrillation. For the surgeon facing this dreaded complication, it may be a 'once in a lifetime' case. This review aims to describe the clinical problem and evaluate the outcome of different surgical techniques to start guiding cardiothoracic surgeons toward those which offer the best chance of survival. An electronic search retrieved 125 articles containing 195 cases of atrioesophageal fistula secondary to atrial fibrillation ablation. Reports of pericardio-esophageal or mediastino-esophageal fistula were excluded. The median age was 61 and 143 (73%) cases occurred in males. Fever (n = 147; 75%) and neurological dysfunction (n = 151; 77%) were the most common symptoms. The median time from ablation to symptom onset was 21 days (interquartile range: 12-28). The most sensitive thoracic imaging modality was computed tomography (n = 135/153; 90%). Immediate deterioration occurred during 11/58 (19%) oesophago-gastro-duodenoscopies. Mortality was lower in patients who had surgery (39%) compared with endoscopic intervention (94%) or conservative management (97%). Patients who had atrial repair combined with esophageal repair or oesophagectomy were more likely to survive than those who had atrial repair alone (OR 6.97; p < .001). Isolation of the esophageal aspect of the fistula conferred an additional survival benefit (OR 5.85; p = .02). Fever, neurological symptoms, and chest pain in the context of recent ablation should prompt immediate evaluation. Urgent CT thorax should be arranged and repeated if initially unremarkable. Esophageal instrumentation should be avoided due to the risk of catastrophic air embolism or massive hemorrhage. The best way forward is emergency surgical repair; the combination which offers the best survival benefit is atrial repair combined with esophageal surgery and isolation of the esophageal aspect of the fistula.


Thoracodorsal nerve graft for reconstruction of facial nerve branching.
Surgical treatment of parotid malignancies may frequently involve facial nerve amputation to achieve oncological radical resection. The entire facial nerve branching from its exit from the stylomastoid foramen to the periphery of the gland is often sacrificed. The first reconstructive strategy is the immediate reconstruction of the facial nerve by directly anastomosing the trunk of the facial nerve to its distal branches by interpositional nerve grafting. The present study was performed to determine the adequacy of thoracodorsal nerve grafting for immediate repair of the facial nerve. The anatomical features of the thoracodorsal nerve make it particularly appropriate to match its trunk to the stump of the facial nerve at its exit from the stylomastoid foramen. Up to seven branches of the thoracodorsal nerve may be distally anastomosed to the severed distal branches of the facial nerve. More complex reconstruction may be addressed simultaneously by contemporary harvesting a de-epithelialized free flap from the same site based on thoracodorsal vessel perforators and preparing a rib graft from the same donor site. Between October 2003 and August 2010, seven patients affected by parotid tumors (6 with parotid malignancies and 1 with multiple recurrences of pleomorphic adenoma) underwent radical parotidectomy with intentional sacrifice of the facial nerve to obtain oncological radical resection. In all patients, the facial nerve was reconstructed with an interpositional thoracodorsal nerve graft. In four patients, a de-epithelialized free flap based on the latissimus dorsi was transposed to cover soft tissue defects. Moreover, two of these patients also required a rib graft to reconstruct both the condyle and ramus of the mandible. With the exception of one patient affected by recurrent pleomorphic adenoma, all patients underwent radiotherapy after surgical treatment. All patients in our study recovered mimetic facial function. Facial muscles showed clinical signs of recovery within 5-14 (mean: 7.8) months, with varying degrees of mimetic restoration, and almost complete facial symmetry at rest in all patients. The House-Brackmann final score was I in two patients, II in two patients, and III in three patients. A thoracodorsal nerve graft to replace extratemporal facial nerve branching is a valid alternative technique to multiple classical nerve grafts, with good matching at both the proximal and distal anastomoses.


High tibial osteotomy: long term survival analysis and patients' perspective.
High tibial osteotomy has been generally accepted as a useful treatment for unicompartment osteoarthritis of the knee to improve a patient's quality of life. Few studies have examined the outcome from the patient's perspective. A survival analysis of one to twenty-one years was conducted on 67 knees including analysis of the patients' satisfaction level with this procedure. Cumulative survival probability of 89.5% at 5 years, 74.7% at 10 years and 66.9 % for 15 and 20 years was reported. Ninety-one percent of patients had improvement in pain score and would choose to have this surgery again. Average patient satisfaction level was 75.5%. Forty-eight percent of patients were able to perform at a higher level of activity than before surgery, although none was able to perform at the level prior to the onset of knee pathology. It was concluded that this procedure was able to improve a patient's quality of life and achieved high satisfaction among patients. There is an increasing role of high tibial osteotomy as an adjunct to an autologous chondrocyte implantation procedure.


Distribution and accumulation of major and trace elements in water, sediment, and fishes from protected areas of the Atlantic Rainforest.
Environmental pollution affects the quality of the natural environment where major and trace elements have been commonly found to accumulate in biotic and abiotic matrices. The purposes of this research were (1) to assess the accumulation and distribution of 24 major and trace elements in water, sediments, and muscle and gills of ten native fishes from two natural areas with different degree of protection in the Atlantic Rainforest, (2) to discuss potential origin of the elements related to the land use, and (3) to assess the human health risk for water and muscle fish consumption in general and fisher populations. Major and trace elements were determined by inductively coupled plasma mass spectrometry. Concentrations of Ag, Cu, and Se in water and Cr, Cu, Hg, Mn, Ni, and Zn in sediment were higher than the international guidelines for the aquatic biota protection. Muscle Cr, Cu, Ni, Pb, Hg, and Zn from several species (both studied areas) were above guidelines for human consumption. The bioaccumulation factor (< 6936) was higher in gills than in muscle, and indicated that Andromakhe saguazu, Andromakhe paris, Gymnogeophagus lipokarenos, and Steindachnerina biornata were macroconcentrators of Zn, and Australoheros ykeregua, G. lipokarenos, and Hemiancistrus fuliginosus were macroconcentrators of Se and Sr. The hazard index and target hazard quotient indicated that there is no risk from chronic consumption of water or fish. The results show the need to reduce the entry of pollutants into streams, paying special attention to reducing runoff in deforested areas.


What's new in malignant tumors in acquired immunodeficiency disorders?
An increased incidence of malignant tumors has long been recognized in patients with primary immune defects such as the X-linked lympho-proliferative syndrome or the Wiskott Aldrich syndrome and has recently become a major concern also in cases with acquired immunodeficiency. The latter may be induced by cytostatic therapy for cancer, extended immunosuppression following organ transplantation or HIV infection. The spectrum of secondary cancers is, however, different within these three groups of secondary immune defects with acute myeloid leukemia being the most common malignant disease after cytostatic therapy, with skin or lip cancer followed by non-Hodgkin's lymphoma as the prevalent malignancies after organ transplantations and Kaposi sarcoma and non-Hodgkin's lymphoma as the predominant cancers associated with HIV infection. The pathogenesis of Kaposi sarcoma and non-Hodgkin's lymphoma is possibly related to viral infections by cytomegalovirus and Epstein-Barr virus inducing an increased proliferation and possibly the coactivation of transforming genes of oncogenic potential. In AIDS patients Kaposi sarcoma is diagnosed in up to 40% of homosexual men while the other risk groups are less frequently involved. 4-10% of HIV infected patients experience non Hodgkin's lymphoma predominantly of B-cell type and intermediate or high grade malignancy with frequent extranodal manifestations. Other types of tumors occur at a substantially lower frequency and are not clearly related to the HIV infection. The overall survival of patients suffering from malignant tumors in the state of immunodeficiency is poor and the possibilities for therapeutic intervention are limited by the risk of accelerating the pre-existing suppression of defense mechanisms.


5-azacytidine induction of thymidine kinase in a spontaneously enzyme-deficient murine tumor line.
During the course of our studies on murine tumor cell metastases, one of our variant lines (called L61-M) was found to be unable to incorporate [methyl-3H]thymidine into DNA, due to a spontaneous deficiency in thymidine kinase (TK) activity. L61-M cells are unable to proliferate in HAT selection medium and are resistant to bromodeoxyuridine (BrdU). TK activity in L61-M cells is 4.2% of that found in the wild-type parental MDAY-D2 cell line. Treatment of L61-M with 5-azacytidine, a known inducer of DNA hypomethylation, resulted in the expression of TK activity. These observations suggest that the TK deficiency in the L61-M cell line was due in part to an alteration in the methylation pattern of DNA, resulting in the diminished expression of the TK gene. These results demonstrate the ability of 5-azacytidine to induce TK activity in a spontaneously enzyme-deficient murine tumor cell line.


Impact of Medicaid Expansion on Abdominal Surgery Morbidity, Mortality, and Hospital Readmission.
Medicaid expansion's (ME) impact on postoperative outcomes after abdominal surgery remains poorly defined. We aimed to evaluate ME's effect on surgical morbidity, mortality, and readmissions in a state that expanded Medicaid (Virginia) compared to a state that did not (Tennessee) over the same time period. Virginia Surgical Quality Collaborative (VSQC) American College of Surgeons National Surgical Quality Improvement Program data for Medicaid, uninsured, and private insurance patients undergoing abdominal procedures before Virginia's ME (3/22/18-12/31/18) were compared with post-ME (1/1/19-12/31/19), as were corresponding non-ME state Tennessee Surgical Quality Collaborative (TSQC) data for the same 2018 and 2019 time periods. Postexpansion odds ratios for 30-d morbidity, 30-d mortality, and 30-d unplanned readmission were estimated using propensity score-adjusted logistic regression models. In Virginia, 4753 abdominal procedures, 2097 pre-ME were compared to 2656 post-ME. In Tennessee, 5956 procedures, 2484 in 2018 were compared to 3472 in 2019. VSQC's proportion of Medicaid population increased following ME (8.9% versus 18.8%, P < 0.001) while uninsured patients decreased (20.4% versus 6.4%, P < 0.001). Post-ME VSQC had fewer 30-d readmissions (12.2% versus 6.0%, P = 0.013). Post-ME VSQC Medicaid patients had significantly lower probability of morbidity (-8.18, 95% confidence interval: -15.52 ∼ -0.84, P = 0.029) and readmission (-6.92, 95% confidence interval: -12.56 ∼ -1.27, P = 0.016) compared to pre-ME. There were no differences in probability of morbidity or readmission in the TSQC Medicaid population between study periods (both P > 0.05); there were no differences in mortality between study periods in VSQC and TSQC patient populations (both P > 0.05). ME was associated with decreased 30-d morbidity and unplanned readmissions in the VSQC. Data-driven policies accounting for ME benefits should be considered.


Delinquency prevention in the 1980s.
Current American delinquency prevention strategies adopted by the federal Office of Juvenile Justice and Delinquency Prevention emphasize trying to change organizations (especially schools) rather than individuals. Similarly, the report by Rutter and Giller to the Home Office and the Department of Health and Social Security advocates changes in the school, the area, the community or the physical environment. It is argued here that it is just as plausible to locate the causes of delinquency in the individual as in the environment, and that there is good reason to expect delinquency prevention efforts targeted on individuals to be successful. Pre-school early intervention programmes designed to increase intellectual ability are especially desirable.


Transcriptome analysis of immune response genes induced by pathogen agonists in the Antarctic bullhead notothen Notothenia coriiceps.
Fish are a representative population of lower vertebrates that serve as an essential link to early vertebrate evolution, and this has fueled academic interest in studying ancient vertebrate immune defense mechanisms in teleosts. Notothenia coriiceps, a typical Antarctic notothenioid teleost, has evolved to adapt to the cold and thermally stable Antarctic sea. In this study, we examined adaptive signaling pathways and immune responses to bacterial and viral pathogenic exposure in N. coriiceps. Using RNA sequencing, we investigated transcriptional differences in the liver tissues of N. coriiceps challenged with two pathogen-mimicking agonists, a bacterial ligand (heat-killed Escherichia coli, HKEB) and a viral ligand (polyinosinic:polycytidylic acid, Poly I:C). We found that 567 unique genes were up-regulated two-fold in the HKEB-exposed group, whereas 392 unique genes, including 124 immune-relevant genes, were up-regulated two-fold in the Poly I:C-exposed group. A KEGG pathway analysis of the 124 immune-relevant genes revealed that they exhibited major features of antigen processing and presentation bacterial ligand exposure, but they were down-regulated after viral ligand exposure. A quantitative real time RT-PCR analysis revealed that TNFα and TNF2, major inducers of apoptosis, were highly up-regulated after exposure to the viral ligand but not the bacterial ligand. The results suggest that the bacterial and viral ligands up-regulate inducers of different immune mechanisms in N. coriiceps liver tissue. N. coriiceps has an immune response defense strategy that uses antigen presentation against bacterial infection, but it may use a different defense, such as TNF-mediated apoptosis, against viral infection. The specific immune responses of N. coriiceps may be adaptations to the Antarctic environment and pathogens. These results will help define the characteristics of Antarctic fish and increase our understanding of their immune response mechanisms.


Handedness anomaly in a non-collinear antiferromagnet under spin-orbit torque.
Non-collinear antiferromagnets are an emerging family of spintronic materials because they not only possess the general advantages of antiferromagnets but also enable more advanced functionalities. Recently, in an intriguing non-collinear antiferromagnet Mn3Sn, where the octupole moment is defined as the collective magnetic order parameter, spin-orbit torque (SOT) switching has been achieved in seemingly the same protocol as in ferromagnets. Nevertheless, it is fundamentally important to explore the unknown octupole moment dynamics and contrast it with the magnetization vector of ferromagnets. Here we report a handedness anomaly in the SOT-driven dynamics of Mn3Sn: when spin current is injected, the octupole moment rotates in the opposite direction to the individual moments, leading to a SOT switching polarity distinct from ferromagnets. By using second-harmonic and d.c. magnetometry, we track the SOT effect onto the octupole moment during its rotation and reveal that the handedness anomaly stems from the interactions between the injected spin and the unique chiral-spin structure of Mn3Sn. We further establish the torque balancing equation of the magnetic octupole moment and quantify the SOT efficiency. Our finding provides a guideline for understanding and implementing the electrical manipulation of non-collinear antiferromagnets, which in nature differs from the well-established collinear magnets.


[Anti-tumor effect of ethanol extracts from Thymus quinquecostatus Celak on human leukemia cell line].
To screen the anti-tumor fraction of ethanol extracts from Thymus quinquecostatus Celak and investigate its anti-tumor effect on human leukemia cell line. Ethyl acetate, n-butanol and acetone fractions were separated from the ethanol extracts of wild Thymus quinquecostatus Celak. Growth inhibiting effects of these extracts on human leukemia cell lines K562 and HL-60 were determined by live cell counting and cell growth curve analysis. The possible anti-tumor mechanism was studied by morphological analysis with norcantharidin as a positive control. Ethyl acetate fraction could significantly inhibit the proliferations of K562 and HL-60 cells, and the inhibiting effect depended on the concentration of ethyl acetate fraction. Ethyl acetate fraction could induce apoptosis of K562 and HL-60 cells. The n-butanol and acetone fractions had no significant inhibiting effect on K562 and HL-60 cells. Ethyl acetate fraction is the major anti-tumor fraction in ethanol extracts from Thymus quinquecostatus Celak.


Vertical dysplasias and myofascial pain dysfunction syndrome.
The word myofascial describes the muscles (myo, Greek) and connecting tissue (fascia, Latin) of the face. This article discusses a group of symptoms that involves pain in the muscles around the face.


Entry of lomefloxacin and temafloxacin into human neutrophils, peritoneal macrophages, and tissue culture cells.
The uptake of lomefloxacin (difluoroquinolone) and temafloxacin (trifluoroquinolone) by human polymorphonuclear leukocytes (PMNs), peritoneal macrophages (PM phis), and two tissue culture cells (McCoy and Vero) was measured by a fluorometric assay. Both antimicrobials reached high intracellular concentrations in PMNs [cellular to extracellular ratio (C/E) greater than 4], in PM phis (C/E greater than 3) and lower in tissue culture cells (C/E greater than 1) at an extracellular concentration of 5 mg/L. Lomefloxacin uptake by PMNs was more rapid than that of temafloxacin. Entry of both quinolones into PMNs was environmental temperature-dependent, but not affected by cell viability. Ingestion of opsonized Staphylococcus aureus did not affect the ability of PMNs to concentrate these antimicrobials. Ingestion of opsonized zymosan or stimulation with phorbol myristate acetate significantly increased the PMN association of both quinolones, this effect being particularly marked with temafloxacin. It is concluded that both lomefloxacin and temafloxacin are markedly concentrated within human phagocytes and tissue culture cells, although this phenomenon is not dependent on the degree of fluorination of the molecule.


Protein domain structure uncovers the origin of aerobic metabolism and the rise of planetary oxygen.
The origin and evolution of modern biochemistry remain a mystery despite advances in evolutionary bioinformatics. Here, we use a structural census in nearly 1,000 genomes and a molecular clock of folds to define a timeline of appearance of protein families linked to single-domain enzymes. The timeline sorts out enzymatic recruitment, validates patterns in metabolic history, and reveals that the most ancient reaction of aerobic metabolism involved the synthesis of pyridoxal 5'-phosphate or pyridoxal and appeared 2.9 Gyr ago. The oxygen source for this primordial reaction was probably Mn catalase, which appeared at the same time and could have generated oxygen as a side product of hydrogen peroxide detoxification. Finally, evolutionary analysis of transferred groups and metabolite fragments revealed that oxidized sulfur did not participate in metabolism until the rise of oxygen. The evolutionary patterns we uncover in molecules and chemistries provide strong support for the coevolution of biochemistry and geochemistry.


Factors Associated With Increased Opioid Prescriptions Following Anterior Cruciate Ligament Reconstruction in Opioid-Naïve Patients.
To identify the mean morphine milligram equivalent (MME) opioid prescriptions for opioid-naïve patients undergoing isolated anterior cruciate ligament reconstruction (ACLR) between 4 weeks before surgery and the first 90 days after surgery and to describe opioid prescriptions filled per patient and mean MMEs per year within 90 days following ACLR. Exclusion criteria were patients having concurrent other cruciate or collateral ligament repair or reconstruction, meniscus procedures (repair and debridement), any cartilage procedure, lower-extremity osteotomy, or knee procedures for fracture, infection, or neoplasms; patients with substance use disorder or chronic pain also were excluded. Opioid use between 4 weeks before surgery and the first 90 days after surgery was recorded. Prescribing physician specialty also was tracked. The correlation of patient factors and prescriber specialty of MME were compared using the Student's t-test. Significance was defined at P < .05. Opioid-naïve patients undergoing isolated ACLR were included. Isolated arthroscopic ACLRs performed between 2010 and Q3 2020 in opioid-naïve patients were identified within the PearlDiver M91 national database. A total of 37,200 patients were identified. Mean MME per patient was 340.9 ± 198.2, with an average MME per day of 59.9. Factors associated with increased opioid use during the 90 days following ACLR were older age (P < .001) and preoperative diagnosis of depression (P < .001). Orthopaedic surgeons were primarily responsible for the number of opioid prescriptions after ACLR (n = 29,326, 73.0%) but 27% (n = 10,797) of prescriptions came from nonorthopaedic surgeon medical providers who prescribed significantly greater MMEs of opioids than orthopaedic surgeons (456.5 vs 339.2, P < .001) per patient. Lastly, decreasing yearly opioid prescriptions per patient (2.4 to 1.6 prescriptions) and the mean MME per patient (428.4 to 257.1) occurred from 2010 to 2020. Older age and preoperative diagnosis of depression are associated with greater opioid doses after ACLR. In addition, the vast majority of opioid prescriptions are written by orthopaedic surgeons on the day of ACLR and decreased considerably by four weeks after surgery. Patients receiving opioid prescriptions by nonorthopaedic surgeon medical providers receive significantly greater doses. Level IV, retrospective cohort study.


A new efficient route for the formation of quinoxaline N-oxides and N,N'-dioxides using HOF.CH3CN.
HOF.CH3CN, a very efficient oxygen-transfer agent made readily from fluorine and aqueous acetonitrile, was reacted with various quinoxaline derivatives to give the corresponding mono N-oxides and especially the N,N'-dioxides in very good yields under mild conditions and short reaction times.


In vitro myelin basic protein synthesis in the PNS and CNS of myelin deficient (mld) mutant mice.
The CNS of the mutant mld has a severe myelin deficit. In contrast, myelination is normal in the PNS. Previous studies showed that myelin basic proteins (MBP) are practically missing in mld CNS and PNS tissues. Using an in vitro system and immunoprecipitation, we present evidence that MBP synthesis is repressed in the PNS and in the CNS of mld mutants.


Awareness of Iranian's General Dentists Regarding the Latest Prophylaxis Guideline for Prevention of Infective Endocarditis.
Statement of Problem : Dental procedures leading to oral tissue injuries may provoke bacterial release to the blood stream causing infective endocarditis (IE) in vulnerable patients. The guideline which was proposed by AHA has been updated 9 times having the last update published in 2007. This study was endeavored to uncover the level of knowledge of general dental practitioners in Shiraz, concerning the 2007 AHA guidelines for endocarditis prophylaxis in patients with cardiac problems receiving dental treatments. This cross- sectional and descriptive analytical study included 150 dentists as participants. All practitioners were given a self -report questionnaire which consisted of three sections. Questions were designed to assess their knowledge of antibiotic prophylaxis in patients with cardiac disease. Almost all participants (93%) were aware of antibiotic prophylaxis to be essential for tooth extraction. Most participants did not believe in prophylaxis for noninvasive procedures (such as shedding of primary teeth, impression, intraoral radiography). From all of the respondents, 75% considered Amoxicillin to be the antibiotic of choice and 57% were acquainted with the correct dose of Amoxicillin for high risk patients. The study identified a potential for under/over prescription of antibiotic prophylaxis under the current guideline. Burden of IE necessitates more accurate knowledge of antibiotic prophylaxis in the undergraduate curriculum and continuing education programs of dentistry.


Torrefaction of invasive alien plants: Influence of heating rate and other conversion parameters on mass yield and higher heating value.
With the aim of controlling their proliferation, two invasive alien plants, Lantana camara (LC) and Mimosa pigra (MP), both widespread in Africa, were considered for torrefaction for renewable energy applications. Using thermogravimetric analysis, the influence of heating rate (HR: 2.18-19.82°Cmin(-1)) together with variable temperature and hold time on char yield and HHV (in a bomb calorimeter) were determined. Statistically significant effects of HR on HHV with optima at 10.5°Cmin(-1) for LC and 20°Cmin(-1) for MP were obtained. Increases of HHV up to 0.8MJkg(-1) or energy yield greater than 10%, together with a 3-fold reduction in torrefaction conversion time could be achieved by optimisation of HR. Analysis of the torrefaction volatiles by TG-MS showed that not only hemicelluloses, but also lignin conversion, could influence the optimum HR value.


Anxiety and depression: main determinants of health-related quality of life in Brazilian patients with Parkinson's disease.
Determinants of health-related quality of life (HRQoL) were assessed in 115 Brazilian patients (56.5% males; mean age 62.5 years) with Parkinson's disease (PD). Hoehn and Yahr (H&Y) staging, Scales for Outcomes in Parkinson's Disease-Motor Scale (SCOPA-MS), Cumulative Illness Rating Scale-Geriatrics, Hospital Anxiety and Depression Scale (HADS), Parkinson's Disease Questionnaire (PDQ-39), and SCOPA-Psychosocial Questionnaire (SCOPA-PS) were applied. Median H&Y was 3 and the SCOPA-MS score was 25.6+/-13.1. The proportion of patients who scored > or =11 points in the HADS-Depression and HADS-Anxiety subscales were 47% and 30.4%, respectively. In the multivariate model, HADS-Anxiety or HADS-Depression (p<0.0001), disability (SCOPA-MS II) (p=0.0001) and comorbidity (p=0.0005) were independently associated to PDQ-39 and SCOPA-PS. Mood disturbances were the main determinants of HRQoL.


Three-dimensional angiographic imaging of leakage in branch retinal vein occlusion.
Optical coherence tomography (OCT) is used to image branch retinal vein occlusion (BRVO) but lacks information about leakage dynamics and perfusion status. Topographical angiography (TAG) is capable of providing this information and has been described previously in age-related macular degeneration. This study evaluates TAG in BRVO. We included 56 eyes of 40 consecutive patients with BRVO and a reduction in central vision. Two groups were established based on whether argon laser coagulation was performed or not. A standardized follow-up was performed. The chorioretinal fluorescence pattern was reconstructed following TAG. Quantitative measurements were also performed. TAG performed from indocyanine green angiography (ICGA) showed smaller lesion size (LS) compared to fluorescein angiography (FA) (mean difference: early phase = -1.6 mm(2), late phase = -1.8 mm(2)). The extent of mean LS from early to late phase increased by 0.8 mm(2) in FA and by 0.6 mm(2) in ICGA. TAG could visualize different degrees of leakage topographically. TAG gives new insights into the pathophysiology of BRVO: it enables the visualization of dynamics of leakage and the demonstration of the effects of intravasal stasis. Furthermore, TAG is less impaired by masking phenomena than FA. Functional retinal imaging shows distinct advantages over OCT: quantification of leakage activity is possible using TAG.


[Spanish cultural adaptation and psychometrical validation of the Treatment Benefit Scale (TBS) in the symptomatic treatment of overactive bladder].
Psychometric validation of the Spanish version of the Treatment Benefit Scale (TBS) scale for assessing the patient's treatment benefit on symptoms associated to overactive bladder. The Spanish version of the TBS was administered in the final visit of a prospective observational clinic study, after 3 months of a clinical intervention. Overactive bladder patients, above 18 years old, of both genders, with an OAB-V8 score ≥8, and able to understand health questionnaires in Spanish were recruited. A total of 246 patients (57.7 years, 76% women) were included. The scale was not completed by 1.7% of patients. Extreme improvement was experienced by 30% of patients, 58% improved, 11% did not change, and 2% worsened after medical intervention. The TBS significantly correlated with the clinical criterion of change; (r=0.743; P<.001). A linear association was observed with changes in both OABq-SF scale domains; severity: F(linear)=33.89, P<.001 and health related quality of life: F(linear)=41.69, P<.001. The TBS was able to distinguish between groups of patients by severity and quality of life, F=11.17, P<.001 and F=13.95, P<.001. The Spanish version of the TBS scale has shown good validity psychometric properties in Spanish overactive bladder patients, supporting its use in routinely clinical practice for assessing subjective outputs related to overactive bladder treatment.


ERK-mediated upregulation of matrix metalloproteinase-2 promotes the invasiveness in human oral squamous cell carcinoma (OSCC).
Loco-regional invasion is commonly found in oral squamous cell carcinoma (OSCC) and is associated with its poor survival rate. Matrix metalloproteinase-2 (MMP-2) has been implicated in OSCC progression, but its regulation is poorly understood. Here, one hundred twenty-seven different post-operated human oral cancer tissue samples were analyzed. The messenger RNA (mRNA) expression, protein expression, and MMP-2 activity and MT1-MMP, TIMP-2, and TFs (NFκB, AP1, Sp1, and Twist) were observed semi-quantitative RT-PCR, western blotting, and gelatin zymography. In addition, OSCC derived Cal-27, SCC4/9 cells, photochemical ECGC, and MAPK-pathway inhibitor PD98059 were utilized for in vitro testing and wound healing assay. s: Increased protein and activity level of MMP-2 was detected in non-invasive (N0) and invasive (N1-3) oral tumors as compared to the control (adjacent normal) samples. MMP-2 protein and mRNA expression were positively associated with the TFs and MT1-MMP, negatively associated with TIMP-2 expression. Similarly, the MMP-2 expression/activity was related to several signal-transduction pathways like ERK1/2 and wnt-β-catenin pathways. Treatment of ECGC/MEK inhibitor (PD98059) diminished MMP-2 activity and invasion/migration potential in OSCC. Our research suggests that the ERK1/2 driven overexpression/activation of MMP-2 was linked with the overall OSCC invasion and metastasis. Treatment of MEK inhibitor (PD98059) and ECGC diminished MMP-2 activity and thus could be exploited as a therapeutic strategy to control the invasive OSCC.


In vitro regulation of sheep ovarian surface epithelium (OSE) proliferation by local ovarian factors.
The ovarian surface epithelium (OSE) forms a lining around the entire ovary and actively participates in the ovulatory cycle. To investigate how specific growth factors and hormones affect OSE proliferation, the present study used sheep as a model to examine the effects of follicular and luteal products on the proliferation of sheep OSE cells in culture, and to analyse the influences of large antral follicles and corpora lutea (CL) on the expression of gonadotrophin receptors (FSHR and LHR) in the OSE. In the present study, follicular fluids from medium and large follicles, and extracts of corpora lutea stimulated the growth of OSE cells. The results of the present study showed that factors in the follicular fluid can induce OSE proliferative activity, and this stimulation effect could not be attributed to steroids in the follicular fluid since oestrogen and progesterone treatments failed to stimulate OSE cells. The expression of LH and FSH receptors over large follicles (5 mm or larger) was two and four times higher than those over stroma and CL, respectively. In conclusion, OSE proliferation in cycling sheep is associated with underlying developing follicles and CL, mediated by, at least in part, the up-regulation of gonadotrophin receptors, and facilitated by the action of mitogenic glycopeptides and growth factors, but not steroids.


Covalently Cross-Linked Pig Gastric Mucin Hydrogels Prepared by Radical-Based Chain-Growth and Thiol-ene Mechanisms.
Mucin, a high molecular mass hydrophilic glycoprotein, is the main component of mucus that coats every wet epithelium in animals. It is thus intrinsically biocompatible, and with its protein backbone and the o-glycosidic bound oligosaccharides, it contains a plethora of functional groups which can be used for further chemical modifications. Here, chain-growth and step-growth (thiol-ene) free-radical cross-linked hydrogels prepared from commercially available pig gastric mucin (PGM) are introduced and compared as cost-efficient and easily accessible alternative to the more broadly applied bovine submaxillary gland mucin. For this, PGM is functionalized with photoreactive acrylate groups or allyl ether moieties, respectively. Whereas homopolymerization of acrylate-functionalized polymers is performed, for thiol-ene cross-linking, the allyl-ether-functionalized PGM is cross-linked with thiol-functionalized hyaluronic acid. Morphology, mechanical properties, and cell compatibility of both kinds of PGM hydrogels are characterized and compared. Furthermore, the biocompatibility of these hydrogels can be evaluated in cell culture experiments.


Out of hospital sudden cardiac death in Italy: a population-based case-control study.
Sudden cardiac death (SCD) is a major cause of death in western countries, with coronary heart disease (CHD) being the basis of over 70% of SCD. Incidence in high-CHD risk countries has already been studied, but this information is not available for Mediterranean low-CHD risk countries. Incidence is of paramount importance when cost-effectiveness rate of actions against SCD must be estimated. We estimated the incidence of SCD and its potential risk associated with clinical variables, by a means of a case-control study in a general practice setting. The enrolled general practitioners (GPs) provided data about the total number of their patients, and identified all their patients who suffered an out-of-hospital SCD during the previous 365 days. Two age-matched and gender-matched controls visiting GPs office after the SCD selection were also selected. We used a structured questionnaire to obtain information about potential risk factors for SCD. Covariates that were univariately associated with SCD were included in the multivariate regression analyses. In a population of 297 340 (age greater than 14 years), a total of 230 cases were identified (0.77 per 1000 individuals), mostly occurring at home and among persons with known high cardiovascular risk. In the multivariate analysis only CHD (OR: 1.67; 95% CI: 1.09-2.58), arrhythmia (OR: 2.2; 95% CI: 1.3-3.9), obesity (OR: 2.3; 95% CI: 1.5-3.6), alcohol abuse (OR: 1.8; 95% CI: 1.2-2.7), and family history of CHD (OR 3.1; 95% CI: 1.8-5.3) resulted in a significant association with SCD. The incidence of SCD in Italy is lower than that reported in high-CHD risk population, most of the cases occurring at home and among persons with known high cardiovascular risk. Implementing recommendations for these patients seems to be the most effective strategy to reduce the incidence of SCD.