Acetylation of lysine residues in the recombinant nucleoprotein and VP40 matrix protein of Zaire Ebolavirus by eukaryotic histone acetyltransferases.
Acetylation of histones and other proteins plays crucial roles in transcriptional regulation, chromatin organization, and other biological processes. It has been recently reported that the nucleoprotein (NP) of influenza virus is acetylated in infected cells, and this modification contributes to the RNA polymerization activity of the virus. As the influenza virus, the Ebolavirus contains single-stranded negative-sense RNA as its viral genome, which interacts with NP and other viral proteins. In this study, we performed a series of biochemical experiments and revealed that the recombinant Ebolavirus NP and the viral matrix protein VP40, which binds with NP, were acetylated by eukaryotic histone acetyltransferases, such as P300/CREB-binding protein (P300/CBP) and P300/CBP-associated factor (PCAF), in vitro. Mass spectrometry was used to identify the lysine residues that were potential acetylation targets in NP and VP40. The identified lysine residues in NP were located in the RNA-binding cleft and the VP35-binding domain. Potentially acetylated lysine targets in VP40 were identified in the basic patch, which is necessary for constructing oligomers. These results suggest that the acetylation of these lysine residues is involved in the interactions between viral proteins.


Clinical Significance of Molecular Alterations and Systemic Therapy for Meningiomas: Where Do We Stand?
Meningiomas are common intracranial tumors that can be treated successfully in most cases with surgical resection and/or adjuvant radiotherapy. However, approximately 20% of patients show an aggressive clinical course with tumor recurrence or progressive disease, resulting in significant morbidity and increased mortality. Despite several studies that have investigated different cytotoxic agents in aggressive meningiomas in the past several years, limited evidence of efficacy and clinical benefit has been reported thus far. Novel molecular alterations have been linked to a particular clinicopathological phenotype and have been correlated with grading, location, and prognosis of meningiomas. In this regard, SMO, AKT, and PIK3CA mutations are typical of anterior skull base meningiomas, whereas KLF4 mutations are specific for secretory histology, and BAP1 alterations are common in progressive rhabdoid meningiomas. Alterations in TERT, DMD, and BAP1 correlate with poor outcomes. Moreover, some actionable mutations, including SMO, AKT1, and PIK3CA, regulate meningioma growth and are under investigation in clinical trials. PD-L1 and/or M2 macrophage expression in the microenvironment provides evidence for the investigation of immunotherapy in progressive meningiomas.


[Electrophoretic study of amylase polymorphism in the ruminal contents and blood serum of sheep and heifers].
Electrophoresis of the investigated materials was carried out in a Shandou SAE soothern 2761 chamber. The amylase activity was demonstrated by the sandwich method on an agar starch substrate. A comparatively best result was obtained with the use of a Celogel carrier, followed by the cellulose-acetate folio and agar. It was found that the rumen liquid had up to 5 amylase-active zones with the use of Celogel or cellulose-acetate folio. The proper conditions for incubation of the substrate were: temperature--45 degrees C, time--1 h, and pH value--5.


Frailty transitions and prevalence in an ageing population: longitudinal analysis of primary care data from an open cohort of adults aged 50 and over in England, 2006-2017.
frailty is common in older adults and is associated with increased health and social care use. Longitudinal information is needed on population-level incidence, prevalence and frailty progression to plan services to meet future population needs. retrospective open cohort study using electronic health records of adults aged ≥50 from primary care in England, 2006-2017. Frailty was calculated annually using the electronic Frailty Index (eFI). Multistate models estimated transition rates between each frailty category, adjusting for sociodemographic characteristics. Prevalence overall for each eFI category (fit, mild, moderate and severe) was calculated. the cohort included 2,171,497 patients and 15,514,734 person-years. Frailty prevalence increased from 26.5 (2006) to 38.9% (2017). The average age of frailty onset was 69; however, 10.8% of people aged 50-64 were already frail in 2006. Estimated transitions from fit to any level of frailty were 48/1,000 person-years aged 50-64, 130/1,000 person-years aged 65-74, 214/1,000 person-years aged 75-84 and 380/1,000 person-years aged ≥ 85. Transitions were independently associated with older age, higher deprivation, female sex, Asian ethnicity and urban dwelling. Mean time spent in each frailty category decreased with age, with the longest period spent in severe frailty at all ages. frailty is prevalent in adults aged ≥50 and time spent in successive frailty states is longer as frailty progresses, resulting in extended healthcare burden. Larger population numbers and fewer transitions in adults aged 50-64 present an opportunity for earlier identification and intervention. A large increase in frailty over 12 years highlights the urgency of informed service planning in ageing populations.


Effect of hot water treatment of beef trimmings on processing characteristics and eating quality of ground beef.
The effect of hot water treatment of beef trimmings on the processing characteristics, shelf-life and consumer acceptability of ground beef was evaluated. Hot water treatment (85°C for 40s) substantially enhanced the microbial quality of trimmings during refrigerated storage and this was independent of the fat level of the trimmings. Treatment had no effect on the oxidative stability of trimmings stored up to 7days, ground beef displayed in a retail cabinet for up to 3days, and had minimal effect on textural properties. Instrumental results demonstrate that ground beef from hot water treated trimmings was slightly lighter and tended to have less red color compared to non-treated beef. These color differences did not impact the consumer acceptance of raw patties, and in addition, hot water treatment did not significantly affect the consumer acceptability of cooked patty attributes.


Synthesis of highly fluorescent carbon quantum dots from rubber seed shells for the adsorption and photocatalytic degradation of dyes.
The potentials of biomass-based carbon quantum dot (CQD) as an adsorbent for batch adsorption of dyes and its photocatalytic degradation capacity for dyes which are congo red (CR) and methylene blue (MB) have been conducted in this study. The CQDs properties, performance, behaviour, and photoluminescence characteristics were assessed using batch adsorption experiments which were carried out under operating conditions including, temperature, pH and dosage. The morphological analysis revealed that CQDs are highly porous, uniform, closely aligned and multi-layered. The presence of hydroxyl, carboxyl and carbonyl functional groups indicated the significance of the oxygenated functional groups. Spectral analysis of photoluminescence for CQDs confirmed their photoluminescent quality by exhibiting high excitation intensity and possessing greenish-blue fluorescence under UV radiation. The removal percentage of the dyes adsorbed for both CR and MB dyes was 77% and 75%. Langmuir isotherm and pseudo-second-order models closely fitted the adsorption results. Thermodynamics analysis indicated that the adsorption process was exothermic and spontaneous, with excellent reusability and stability. The degradation efficiency of CQDs on both dyes was more than 90% under sunlight irradiation and obeyed the first-order kinetic model. These results demonstrated CQDs to be an excellent adsorbent and outstanding photocatalyst for organic dye degradation.


Bioengineered chitosan-magnesium nanocomposite: A novel agricultural antimicrobial agent against Acidovorax oryzae and Rhizoctonia solani for sustainable rice production.
Chitosan is a potent biopolymer having promising antimicrobial properties against phytopathogens. Recently, engineered nanomaterials (ENMs) have gained much attention due to their potential application in the plant disease management. In this study, we reported the green synthesis of chitosan-magnesium (CS-Mg) nanocomposite and its antimicrobial activity against two rice pathogens namely Acidovorax oryzae and Rhizoctonia solani for the first time. The green MgO nanoparticles synthesized by using a native Bacillus sp. strain RNT3, were used to fabricate CS-Mg nanocomposite utilizing one-pot synthesis method. The synthesis of CS-Mg nanocomposite was further confirmed by using UV-vis spectroscopy, whereas, FTIR and XRD analysis showed the capping of CS-Mg nanocomposites by different functional groups together with their crystalline structure, respectively. Besides, SEM and TEM images revealed the spherical shape along with the particles size ranging from 29 to 60 nm. Moreover, EDS analysis confirmed the elemental purity of nanocomposite. The CS-Mg nanocomposite showed remarkable antimicrobial activity against A. oryzae and R. solani and significantly inhibited the growth as compared to non-treated control. The ultrastructure studies showed damaged structure of cell wall and internal cellular organelles after treatment with 100 μg mL-1 CS-Mg nanocomposite. The results of this study indicated that CS-Mg nanocomposite-based antimicrobial agents could be considered as promising nanopesticides against phytopathogens in plant disease management.


Modification of hydrophobic sorbents by cobalt chloride in order to concentrate low molecular polar organic substances from the air for subsequent gas chromatographic determination.
The article presents a new method of modification of hydrophobic sorbents. To improve sorption pre-concentration of polar organic compounds in the air analysis, these sorbents are coated with cobalt chloride. This modification increases retention volume of lower alcohols by 5-10 fold as compared to that of unmodified sorbents and solves the problem of gas-chromatographic determination at 1-2 ppb (micrograms/m(3)) by using the most common flame ionization detector. It should be noted that the modification of hydrophobic sorbents by cobalt chloride has little influence on their porosimetry parameters (specific surface area, proportions of meso- and micropores) and modified sorbents are capable of retaining hydrophobic nonpolar and weakly polar analytes as well as original unmodified sorbents. Thus, a fairly simple procedure leads to a large positive effect.


Therapeutic guidelines on ulcerative colitis: a GRADE methodology based effort of GETECCU.
Evidence-based clinical guidelines on Ulcerative colitis (UC) have been developed through a consensus, while GRADE methodology is the current standard for guideline development. This is the first one based on GRADE methodology on UC. Following GRADE methodology, the Spanish Group of Ulcerative Colitis and Crohn's disease (GETECCU) have developed a guideline on UC treatment. After selection of relevant clinical scenarios, 32 clinical questions were chosen and recommendations were established. In 2 questions no recommendation was possible. Twenty-two actions were recommended for, 14 strongly and 8 weakly. However, in 8 questions a recommendation against doing something was obtained, weak in 5 and strong in 3. The majority of recommendations were based on moderate quality evidence, and only 5 on high-quality evidence. With GRADE methodology we find a clear recommendation on possible actions in most clinical decisions in UC treatment, but much more clinical high-quality research is needed.


Enhanced anti-tumor effect of combination therapy with gemcitabine and apigenin in pancreatic cancer.
Apigenin is a dietary flavonoid possessing therapeutic potential against cancers. This study was designed to investigate whether combination therapy with gemcitabine and apigenin enhanced anti-tumor efficacy in pancreatic cancer. In vitro, the combination treatment resulted in more growth inhibition and apoptosis through the down-regulation of NF-kappa B activity with suppression of Akt activation in pancreatic cancer cell lines (MiaPaca-2, AsPC-1). In vivo, the combination therapy augmented tumor growth inhibition through the down-regulation of NF-kappa B activity with the suppression of Akt in tumor tissue. The combination of gemcitabine and apigenin enhanced anti-tumor efficacy through Akt and NF-kappa B activity suppression and apoptosis induction.


Investigation of the relationship between steps required to stop and propulsive force using simple walking models.
To prevent falls in the elderly, it is essential to evaluate their gait stability and identify factors that negatively affect it. Although one of the probable factors is a decrease in propulsive force of walking, the relationship between the force and the gait stability has not been fully clarified. To this end, two simple walking models were used to investigate the relationship between the propulsive force and the number of steps required to stop, denoted N. N was calculated as the number of steps required for the rimless wheel to stop and was treated as a variable which is an indirect indicator of stability. A lower N corresponds to the gait being closer to a stopped state. The propulsive force was calculated using the push-off impulse applied to the simplest walking model during the step-to-step transition. To account for the effects of the double support phase in human walking, the gravitational impulse, which is the integral of the body weight (gravitational force) over the double support time, was applied to the step-to-step transition equation of the models. The models revealed that the propulsive force is reduced by two factors: the reduction in step length and the reduction in walking speed. In the former, N increases; in the latter, N decreases. The former is consistent with previous experimental results on human gait, whereas the latter has not been experimentally investigated. These results may provide important insights in clarifying the relationship between the stability and the propulsive force in human gait.


Gibberellin A1 metabolism contributes to the control of photoperiod-mediated tuberization in potato.
Some potato species require a short-day (SD) photoperiod for tuberization, a process that is negatively affected by gibberellins (GAs). Here we report the isolation of StGA3ox2, a gene encoding a GA 3-oxidase, whose expression is increased in the aerial parts and is repressed in the stolons after transfer of photoperiod-dependent potato plants to SD conditions. Over-expression of StGA3ox2 under control of constitutive or leaf-specific promoters results in taller plants which, in contrast to StGA20ox1 over-expressers previously reported, tuberize earlier under SD conditions than the controls. By contrast, StGA3ox2 tuber-specific over-expression results in non-elongated plants with slightly delayed tuber induction. Together, our experiments support that StGA3ox2 expression and gibberellin metabolism significantly contribute to the tuberization time in strictly photoperiod-dependent potato plants.


An electronic linkage system for health behavior counseling effect on delivery of the 5A's.
A variety of factors limit the ability of clinicians to offer intensive counseling to patients with unhealthy behaviors, and few patients (2%-5%) are referred to the community counseling resources that do offer such assistance. A system that could increase referrals through an efficient collaborative partnership between community programs and clinicians could have major public health implications; such was the subject of this feasibility evaluation. At nine primary care practices, an electronic linkage system (eLinkS) was instituted to promote health behavior counseling and to automate patient referrals to community counseling services. Patients were offered 9 months of free counseling for weight loss, smoking cessation, and problem drinking at a choice of venues: group counseling, telephone counseling, computer care, and usual care. The delivery of behavioral counseling, measured by the 5A's (ask, address, advise, assess, agree, arrange) and patients' reported experiences with eLinkS, was examined. For 5 weeks eLinkS was used, until high referral volumes depleted counseling funds. Of the 5679 patients visiting the practices, 71% had an unhealthy behavior. Of these patients, 10% were referred for intensive counseling from a community program, most often for weight loss. Counseling and referrals occurred regardless of visit type--wellness, acute, or chronic care. eLinkS was used more often for middle-aged adults and women and by more-experienced clinicians. The intervention increased the rate at which patients were referred for intensive behavioral counseling compared to current practice norms. Given the evidence that intensive counseling is more effective in promoting behavior change, implementing eLinkS could have substantial public health benefits.


A novel semiconductor compatible path for nano-graphene synthesis using CBr4 precursor and Ga catalyst.
We propose a novel semiconductor compatible path for nano-graphene synthesis using precursors containing C-Br bonding and liquid catalyst. The unique combination of CBr4 as precursor and Ga as catalyst leads to efficient C precipitation at a synthesis temperature of 200 °C or lower. The non-wetting nature of liquid Ga on tested substrates limits nano-scale graphene to form on Ga droplets and substrate surfaces at low synthesis temperatures of T ≤ 450 °C and at droplet/substrate interfaces by C diffusion via droplet edges when T ≥ 400 °C. Good quality interface nano-graphene is demonstrated and the quality can be further improved by optimization of synthesis conditions and proper selection of substrate type and orientation. The proposed method provides a scalable and transfer-free route to synthesize graphene/semiconductor heterostructures, graphene quantum dots as well as patterned graphene nano-structures at a medium temperature range of 400-700 °C suitable for most important elementary and compound semiconductors.


Resorbable materials of poly(L-lactide). VII. In vivo and in vitro degradation.
In vivo and in vitro degradation of high molecular weight poly(L-lactide) used for internal bone fixation has been investigated. Within 3 months as-polymerized, microporous PLLA (Mv = 6.8-9.5 X 10(5] exhibited a massive strength-loss (sigma b = 68-75 MPa to sigma b = 4 MPa) and decrease of Mv (90-95%). At week 39, the first signs of resorption were evident (mass-loss 5 wt%). Except for dynamically loaded bone plates no differences between in vivo and in vitro degradation of PLLA were observed. The increase of crystallinity of PLLA upon degradation (up to 83%) is likely to be attributed to recrystallization of tie-chain segments. A more ductile PLLA exhibiting a lower rate of degradation was prepared by extraction of low molecular weight compounds with ethyl acetate.


What are the perspectives of speech pathologists, occupational therapists and physiotherapists on using telehealth videoconferencing for service delivery to children with developmental delays? A systematic review of the literature.
To identify the attitudes and perspectives of speech pathologists, occupational therapists and physiotherapists on using telehealth videoconferencing for service delivery to children with developmental delays. Systematic Literature Review. An electronic search of databases Scopus, CINAHL, MEDLINE, PEDro, Speechbite, OTseeker and ScienceDirect was undertaken in October 2020. Articles were compared with eligibility criteria by 2 authors. All articles were appraised for quality and level of evidence. Fourteen studies were deemed to be eligible. Results were synthesised using a narrative analysis. The themes identified were technology, self-efficacy, replacement of face-to-face services, time management, relationships, access and family-centred care. Each of these themes was seen as both a potential barrier and a facilitator when trying to provide services via telehealth. The results in this review cannot be generalised due to small sampling size, low response rates, lack of maximum variation sampling and under-representation of occupational therapists and physiotherapists. Study design was either mixed-methods survey or interview or only survey or interview. Risk of bias in studies was high. Further research is required including comparison studies and cost-benefit analysis.


Stable, recombinant expression of human insulin-like growth factor binding protein-1 (hIGFBP-1) in Chinese hamster ovary (CHO) cells.
Stable expression of human insulin-like growth factor of binding protein-1 (hIGFBP-1)at high levels has been achieved in Chinese hamster ovary (CHO) cells by co-transfection and subsequent co-amplification of expression vectors containing the hIGFBP-1 cDNA and a dihydrofolate reductase (DHFR) cDNA gene into DHFR-deficient cells. Stepwise selection of the DHFR(+) transformants in increasing concentrations of methotrexate (MTX) generated cells which had high copy numbers of the hIGFBP-1 gene (around 100 copies in cells amplified in medium containing 100 nM MTX). Expression of hIGFBP-1 in mixed clones was found to increase with increasing copy number and an apparent correlation between intra- and extracellular levels of hIGFBP-1 produced by these cells was observed. It was further observed that continuous cultivation over eight months in medium supplemented with 100 nM MTX increased the production of hIGFBP-1 25 times. The productivity did not increase further after five more months cultivation in MTX containing medium. A subcloning of this cell line gave clones with an even higher productivity. Further amplification in 500 nM or 1 uM MTX did not increase the hIGFBP-1 production.


Pragmatic Clinic-Based Investigation of Glycemic Variability in Patients With Type 1 Diabetes in Routine Clinical Practice and Its Association With Cardiovascular Autonomic Neuropathy: A Pilot Study.
To evaluate the relationship between markers of glycemic variability (GV), assessed by blinded continuous glucose monitoring (CGM), and cardiovascular autonomic neuropathy (CAN) in patients with type 1 diabetes (T1D). GV indices, such as SD and coefficient of variation were obtained by blinded CGM through an electrode inserted into the subcutaneous tissue for at least 3 consecutive days. CAN was assessed by cardiovascular reflex tests and HRV. Fifteen T1D patients were included: 7 (46.7%) women, aged 47.1 ± 11.6 years, with a diabetes duration of 26 years (20 to 29.5 years). Five patients (25%) were excluded from our study. The majority of our patients presented glycated hemoglobin (60%), SD (86.3%), and coefficient of variation (60%) above the established goals. Patients with defined CAN had a longer diabetes duration, higher glycated hemoglobin levels, lower glomerular filtration rate, lower prevalence of indices related to hypoglycemic stress, and short-term GV indices compared with patients without CAN. Our study showed an inverse association between GV and CAN. The most important risk factors associated with CAN were age, diabetes duration, and markers of chronic hyperglycemia. Furthermore, the difficulty in the interpretation of data extracted from the blinded CGM system, which also requires a minimum of 3 capillary blood glucose measurements for calibration, should be carefully analyzed to ensure the accuracy and usefulness of the blinded CGM system as a tool for diabetes management in developing countries. Further studies are necessary to establish the role of GV in the development of CAN in patients with T1D.


Systematic review of dose-volume parameters in the prediction of esophagitis in thoracic radiotherapy.
With dose escalation and increasing use of concurrent chemoradiotherapy, radiation esophagitis (RE) remains a common treatment-limiting acute side effect in the treatment of thoracic malignancies. The advent of 3DCT planning has enabled investigators to study esophageal dose-volume histogram (DVH) parameters as predictors of RE. The purpose of this study was to assess published dosimetric parameters and toxicity data systematically in order to define reproducible predictors of RE, both for potential clinical use, and to provide recommendations for future research in the field. We performed a systematic literature review of published studies addressing RE in the treatment of lung cancer and thymoma. Our search strategy included a variety of electronic medical databases, textbooks and bibliographies. Both prospective and retrospective clinical studies were included. Information relating to the relationship among measured dosimetric parameters, patient demographics, tumor characteristics, chemotherapy and RE was extracted and analyzed. Eighteen published studies were suitable for analysis. Eleven of these assessed acute RE, while the remainder assessed both acute and chronic RE together. Heterogeneity of esophageal contouring practices, individual differences in information reporting and variability of RE outcome definitions were assessed. Well-described clinical and logistic modeling directly related V(35Gy), V(60Gy) and SA(55Gy) to clinically significant RE. Several reproducible dosimetric parameters exist in the literature, and these may be potentially relevant in the prediction of RE in the radiotherapy of thoracic malignancies. Further clarification of the predictive relationship between such standardized dosimetric parameters and observed RE outcomes is essential to develop efficient radiation treatment planning in locally advanced NSCLC in the modern concurrent chemotherapy and image-guided IMRT era.


The opposing trends of body mass index and blood pressure during 1977-2020; nationwide registry of 2.8 million male and female adolescents.
Elevated blood pressure among adolescents has been shown to be associated with future adverse cardiovascular outcomes and early onset diabetes. Most data regarding systolic and diastolic blood pressure trends are based on surveys of selected populations within 10-20-year periods. The goal of this study was to characterize the secular trend of blood pressure given the rising prevalence of adolescent obesity. This nationwide population-based study included 2,785,515 Israeli adolescents (41.6% females, mean age 17.4 years) who were medically evaluated and whose weight, height and blood pressure were measured, prior to mandatory military service between 1977 and 2020. The study period was divided into 5-year intervals. Linear regression models were used to describe the P for trend along the time intervals. Analysis of covariance was used to calculate means of blood pressure adjusted for body mass index. During the study period, the mean body mass index increased by 2.1 and 1.6 kg/m2 in males and females, respectively (P for trend < 0.001 in both sexes). The mean diastolic blood pressure decreased by 3.6 mmHg in males and by 2.9 mmHg in females (P < 0.001 in both sexes). The mean systolic blood pressure increased by 1.6 mmHg in males and decreased by 1.9 mmHg in females. These trends were also consistent when blood pressure values were adjusted to body mass index. Despite the increase in body mass index over the last four decades, diastolic blood pressure decreased in both sexes while systolic blood pressure increased slightly in males and decreased in females.


On getting it right by being wrong: A case study of how flawed research may become self-fulfilling at last.
Scientists prominently argue that the COVID-19 pandemic stems not least from people's inability to understand exponential growth. They increasingly cite evidence from a classic psychological experiment published some 45 years prior to the first case of COVID-19. Despite—or precisely because of—becoming such a canonical study (more often cited than read), its critical design flaws went completely unnoticed. They are discussed here as a cautionary tale against uncritically enshrining unsound research in the "lore" of a field of research. In hindsight, this is a unique case study of researchers falling prey to just the cognitive bias they set out to study—undermining an experiment's methodology while, ironically, still supporting its conclusion.


Fabrication of Biomass-Derived Carbon Aerogels with High Adsorption of Oils and Organic Solvents: Effect of Hydrothermal and Post-Pyrolysis Processes.
Biomass is the most plentiful and well-utilized renewable carbon resource on the earth. Direct conversion of biomass to carbon aerogel provides a promising approach to develop adsorbent materials. In the present work, the effect of presence of water during hydrothermal treatment and holding temperature during post-pyrolysis process have been investigated for the preparation of carbon aerogels (CAs) using eggplant as raw material. The results showed that the addition of water during hydrothermal treatment was advantageous for the preparation of CA samples with higher surface area and stronger hydrophobicity, resulting in superior adsorption capacities of CAs for both oil and organic solvents compared with that fabricated without the presence of water. The optimized carbon aerogel possessed higher specific surface of 249 m²·g-1 and exhibited excellent hydrophobicity with a water contact angle of 133°. The adsorption capacities of carbon aerogel for oils and organic solvents could reach 35-45 times its own weight. In addition, the adsorbed oil and organic solvents could be recovered by distillation, and the regenerated carbon aerogels samples exhibited the stable performance and outstanding reusability. Therefore, the carbon aerogel has great potential in application of oil recovery and environmental protection.


Ochratoxin A in human blood serum - retrospective long-term data.
In a long-term study (1990-1997) on ochratoxin A (OTA) in human blood serum, 102 serum samples from 36 persons of the Munich Institute for Hygiene and Technology of Food of Animal Origin were analysed by enzyme immunoassay (EIA), and by high performance liquid chromatography (HPLC) for control. Detection limits were at 50 pg/ml (EIA) and 50-70 pg/ml (HPLC), recoveries were 80-120% (EIA) and 30-60% (LC). OTA was detected in 98% (EIA, 368 ± 217 pg/ml) and 93% (HPLC, 271 ± 170 pg/ml) of samples (maximum 1,290 pg/ml). Using published conversion factors for serum/intake estimates (1.34 or 1.97), the mean daily OTA intake of these 36 persons was 493-725 pg/kg bw. Long-term individual mean OTA levels of nine persons ranged from 162 ± 80 pg/ml to 549 ± 172 pg/ml. Our data were compared with published OTA serum levels (1985-2008) for apparently healthy persons from a total of 30 countries. On a worldwide basis, the mean of means for OTA in human serum was estimated to be 700 pg/ml, corresponding to a mean daily OTA intake of 940-1380 pg/kg bw. This level, which was relatively stable over the last decades, is well below published tolerable daily intake values (14,000-18,000 pg/kg bw).


Ten-year clinical and echocardiographic follow-up of third-generation biological prostheses in the aortic position.
PERIMOUNT Magna Ease (Carpentier-Edwards; PME) prostheses have been widely implanted during the past decade for aortic valve replacement (AVR). Although promising results at midterm follow-up were reported, long-term outcome has yet to be confirmed. On this study we aimed to evaluate long-term results in terms of structural valve degeneration (SVD), major clinical outcomes, long-term hemodynamic valve performance, and left ventricular remodeling. From 2010 to 2012, 689 consecutive patients underwent AVR with PME. Complete clinical 10-year follow-up was obtained. The degree of SVD was categorized on the basis of the latest guidelines. Echocardiographic data were analyzed at 1, 5, and 10 years. Competing risk analysis was performed for major events. Cumulative incidence of SVD, reoperation, and endocarditis were also assessed according to prosthetic sizes (19-21-23 mm vs 25-27-29 mm) and age (<65 vs 65-75 vs >75 years old). The overall cumulative incidence reported for SVD ≥2 and reoperation were 3.6% and 1.9% at 10 years, respectively. An early left ventricular reverse remodeling was noted after implantation and confirmed at follow-up. Patients younger than 65 years showed higher cumulative incidence of SVD ≥2 at 10 years compared with patients aged 65 to 75 and older than 75 years (9.7% vs 2.6% vs 2.7%; P = .013), as well as of redo AVR (7.8% vs 3.3% vs 0.4%; P = .002). There was no difference in terms of SVD and redo AVR for different prosthetic size categories (P > .05). The risk of endocarditis was similar among age and size groups. PME provides very good durability at long-term and could be considered one of the high performing third-generation bioprostheses for AVR.


How do host immune responses affect nematode infections?
Host immune responses limit, and in some instances eliminate, nematode infections. There is considerable interest in enhancing these natural processes by the use of antinematode vaccines to achieve control of infection or disease. How nematodes are damaged is unclear. Worms might be damaged directly by effector cells and molecules of the immune system. Alternatively, they might be damaged by the physiological stress of their efforts to resist attack. Separating these possibilities could have important implications for approaches to the control of nematode infections and the disease that they cause.


Cytokine patterns in seropositive and seronegative patients with Echinococcus granulosus infection.
To investigate the involvement of immunological variables, including the Th1/Th2 balance, in the mechanisms underlying seronegativity in cystic echinococcosis (CE), Th1 and Th2 cytokines were evaluated in ELISA determining IFN-gamma, IL-4, -5 and -10 production in peripheral blood mononuclear cell (PBMC) cultures from 16 patients (six seronegative and ten seropositive) with CE and from six healthy donors. Patients who had undetectable antibody levels in their sera invariably produced no IL-5 and scarce IL-4 and -10 (Th2 response); both groups of patients produced similar amounts of IFN-gamma; (Th1 response). The analysis of host clinical features and cyst characteristics shows that these variables do not explain the lack of detectable serum antibody levels. These findings suggest that seronegativity arises because unknown host or parasite factors, or both, cause inadequate Th2 cell activation thus reducing production of Th2 cytokines, including IL-5, the cytokine primarily implicated in immunoglobulin expression in CE.


Targeted Expression of miR-7 Operated by TTF-1 Promoter Inhibited the Growth of Human Lung Cancer through the NDUFA4 Pathway.
Targeted expression of gene technique is an important therapeutic strategy for lung cancer. MicroRNA-7 has been well documented as a promising tumor suppressor but never been test in specific gene-promoter-targeted expression in cancer gene therapy. Here, we first evaluated the efficacy of miR-7 expression operated by the promoter of TTF-1, a lineage-specific oncogene in lung cancer, in vitro using an eukaryotic vector of TTF-1-promoter-operated expression of miR-7 (termed as p-T-miR-7). Interestingly, using a nude mice model, the growth and metastasis of human lung cancer cells in vivo were significantly reduced in remote hypodermic injection of the p-T-miR-7 group, accompanied by increased expression of miR-7 and reduced transduction of the Akt and Erk pathway in situ. Mechanism aspect, global gene expression analysis showed that downregulation of NDUFA4, a novel target of miR-7, contributed to the effects of miR-7 expression operated by TTF-1 promoter on the growth and metastasis of human lung cancer cells, as well as altered transduction of the Akt and Erk pathway. Finally, there was no significant difference in weight or histopathology of other organs. These data provided a basis for development of novel modality of miRNA-based targeted expression therapy against clinical lung cancer.


[Congenital cystic transformation of the common bile duct in children].
By now the world literature counts 955 observations on congenital cystic enlargement of the common bile duct. The authors add 14 own observations of this rather rare pathology. Preoperative diagnosis is still difficult. The intravenous cholegraphy remains the best diagnostic procedure. The choledochocystoduodenostomy is justified by its usefulness and is the most frequently used. The late results of the treatment are good. An unfavourable prognosis is present only in cases with preoperative chronic hepatitis, cholangitis or pancreatitis, as these diseases are likely to aggravate later on.


Protein Arrays III: Reverse-Phase Protein Arrays.
The reverse-phase protein array (RPPA) is to use highly specific antibodies to interrogate pan or posttranslationally modified protein targets, such as phosphorylated proteins, particularly the proteins involved in cell signaling pathways. In this protocol we will cover the preparation of cell (or tissue) lysates, sample printing, antibody validation, antibody interrogation, signal amplification steps, imaging and data analysis. In this protocol, colorimetric catalyzed signal amplification (CSA) chemistry, fluorescence and near-infrared (NIR) based detection methods will be described.


Short-term improvement following dry needle stimulation of tender points in fibromyalgia.
The purpose of this study was to evaluate the short-term efficacy of dry needling therapy in patients severely affected by fibromyalgia. One hundred and twenty fibromyalgia patients were randomly divided into two groups. The control group, 56 women and 4 men, and the dry needling group, 54 women and 6 men, who apart from continuing their medical treatment, also underwent weekly 1-h session of dry needling for 6 weeks. At the beginning of the program, there were significant differences in the age (mean 56.26 years in the dry needling group versus 50.82 years in controls, p = 0.01) and McGill Pain Questionnaire [MPQ] (mean 39.07 in dry needling group versus 42.44 in controls, p = 0.03). At the end of treatment, the experimental group showed significant differences in most tests, including Visual Analogue Scale (VAS) of pain (p = 0.002), VAS of fatigue (p = 0.02), pain of Medical Outcomes Survey Short Form-36 (SF-36) (p = 0.0007), myalgic score (p = 0.0005), pressure pain threshold (p = 0.002), and global subjective improvement (p = 0.00001). Six weeks after the end of the treatment, the dry needling group still showed significant differences in most tests, including VAS of pain (p = 0.01), VAS of fatigue (p = 0.02), pain of SF-36 (p = 0.01), myalgic score (p = 0.00001), pressure pain threshold (p = 0.0004), and global subjective improvement (p = 0.00001). In conclusion, patients severely affected by fibromyalgia can obtain short-term improvements following weekly dry needling for 6 weeks.


Contribution of human and climate change impacts to changes in streamflow of Canada.
Climate change exerts great influence on streamflow by changing precipitation, temperature, snowpack and potential evapotranspiration (PET), while human activities in a watershed can directly alter the runoff production and indirectly through affecting climatic variables. However, to separate contribution of anthropogenic and natural drivers to observed changes in streamflow is non-trivial. Here we estimated the direct influence of human activities and climate change effect to changes of the mean annual streamflow (MAS) of 96 Canadian watersheds based on the elasticity of streamflow in relation to precipitation, PET and human impacts such as land use and cover change. Elasticities of streamflow for each watershed are analytically derived using the Budyko Framework. We found that climate change generally caused an increase in MAS, while human impacts generally a decrease in MAS and such impact tends to become more severe with time, even though there are exceptions. Higher proportions of human contribution, compared to that of climate change contribution, resulted in generally decreased streamflow of Canada observed in recent decades. Furthermore, if without contributions from retreating glaciers to streamflow, human impact would have resulted in a more severe decrease in Canadian streamflow.


'Trainee' evaluation of the English National Training Programme for laparoscopic colorectal surgery.
The aim of this study was to review trainees' opinions of the training they had received through the National Training Programme (NTP). An online questionnaire was distributed to NTP trainees who had completed five or more training episodes within the programme. Demographic data were collected. Opinion was given using a five-point Likert scale (1 = strongly disagree, 2 = disagree, 3 = undecided, 4 = agree, 5 = strongly agree). Percentages, mean values and SD were presented. ANOVA and Mann-Whitney U-tests were used to examine the impact of different factors on ratings and the difference between ratings, respectively. Fifty-four registered trainees fulfilled the inclusion criteria, and 37 (69% response rate) completed the questionnaire. Teaching sessions were organized using an inreach (11%), in-house (11%), outreach (27%) or combination (51%) system of training. Trainees felt that their trainers seldom cancelled sessions (93%), that it was easy to organize (92%) and consent (100%) the patient, and that their hospital was supportive of training (97%). Trainees stated that overall their trainers were excellent at training (Likert scale = 4.71 ± 0.46) and that they received regular feedback (87%). The only variable to have a significant impact on the level of NTP approval was whether the trainee was able to choose his or her trainer (supportive of NTP, chose trainer P = 0.050; critical of NTP, chose trainer P = 0.020). The large majority of trainees was highly satisfied with the training received in this innovative programme, irrespective of region or training structure used, thus demonstrating acceptability of the programme in its current form.


Anopheles culicifacies breeding in polluted water bodies in Trincomalee District of Sri Lanka.
Anopheles culicifacies, the major vector of malaria in Sri Lanka, is known to breed in clean and clear water. The main objective of the study was to detect the breeding habitat diversity of An. culicifacies. Potential larval habitats for Anopheles mosquitoes were surveyed on a monthly basis for 17 months (January 2011-June 2012) in four different selected sampling sites (Murthankulam, Kommnaimottai, Paranamadawachchiya and Kokmotawewa) in Trincomalee District of Sri Lanka. A total of 2,996 larval specimens representing 13 Anopheles species were reported from 16 different breeding habitats. According to density criterion, An. culicifacies, Anopheles subpictus, Anopheles barbirostris, Anopheles peditaeniatus and Anopheles nigerrimus were dominant. Anopheles nigerrimus, An. subpictus and An. peditaeniatus were observed as constant in relation to their distribution. The most productive breeding site for An. culicifacies was drains filled with waste water in remote areas; the second highest productivity was found in built wells. These results indicate that An. culicifacies has adapted to breed in a wide range of water bodies including waste water collections although they were earlier considered to breed only in clean and clear water.


Geochemical behavior of rare earth elements (REE) in urban reservoirs: the case of Funil Reservoir, Rio de Janeiro State, Brazil.
Rare earth elements (REE) have unique chemical properties, which allow their use as geochemical tracers. In this context, the present study aims to assess the role of Funil Reservoir on REE biogeochemical behavior. We collected water samples upstream of the reservoir (P-01) in the city of Queluz, inside the reservoir (P-02), and downstream of Funil Reservoir (P-03) in the city of Itatiaia, RJ. In the field, physicochemical parameters were measured using a probe (pH, temperature, electrical conductivity, and dissolved oxygen). In the laboratory, water samples were filtered (0.45 µm) and properly packed until chemical analysis. Chlorophyll a concentrations were determined by a spectrophotometric method and suspended particulate matter (SPM) by a gravimetric method. Ionic concentrations were determined by ion chromatography technique and REE concentrations were determined by ICP-MS. Chlorophyll a concentrations were higher in Funil Reservoir. Ionic concentrations in Queluz (P-01) suggest anthropic contamination. The sum of REE in the dissolved fraction ranged from 2.12 to 12.22 µg L-1. A positive anomaly of La in Queluz indicates anthropic contamination. The observed patterns indicate that Funil Reservoir acts as a biogeochemical barrier, modifying the fluvial transport of REE. Nonetheless, another factor that probably influences REE behavior is the algal bloom that occurs in reservoirs during the rainy season. The seasonal behavior of algae can influence REE biogeochemistry through the incorporation and release of trace metals.


A compression algorithm for the combination of PDF sets.
The current PDF4LHC recommendation to estimate uncertainties due to parton distribution functions (PDFs) in theoretical predictions for LHC processes involves the combination of separate predictions computed using PDF sets from different groups, each of which comprises a relatively large number of either Hessian eigenvectors or Monte Carlo (MC) replicas. While many fixed-order and parton shower programs allow the evaluation of PDF uncertainties for a single PDF set at no additional CPU cost, this feature is not universal, and, moreover, the a posteriori combination of the predictions using at least three different PDF sets is still required. In this work, we present a strategy for the statistical combination of individual PDF sets, based on the MC representation of Hessian sets, followed by a compression algorithm for the reduction of the number of MC replicas. We illustrate our strategy with the combination and compression of the recent NNPDF3.0, CT14 and MMHT14 NNLO PDF sets. The resulting compressed Monte Carlo PDF sets are validated at the level of parton luminosities and LHC inclusive cross sections and differential distributions. We determine that around 100 replicas provide an adequate representation of the probability distribution for the original combined PDF set, suitable for general applications to LHC phenomenology.


Application of block matching method-based Echocardiography combined with serum NT-PROBNP level detection in the early prediction of PDA in premature infants.
The paper uses block matching method combined with echocardiography to explore the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting symptomatic patent ductus arteriosus (PDA) in preterm infants. We selected premature infants born between February 2019 and March 2020, gestational age ≤32 weeks, and echocardiography within 48 hours to determine the presence of arterial ducts as the research object, monitor their clinical manifestations, and detect serum at three and five days after birth The level of NT-proBNP was checked with echocardiography, and the children were divided into PDA group and asymptomatic patent ductus arteriosus (aPDA) group according to the clinical manifestations and echocardiographic. The area under the ROC curve of PDA predicted by serum NT-proBNP level at 3 days after birth was 0.949, the cut-off value was 27035pg/mL, the sensitivity was 92.3%, and the specificity was 94.6%; serum NT-proBNP level at 5 days after birth predicted the ROC curve of PDA The lower area is 0.924, the critical value is 6411 pg/mL, the sensitivity is 92.3%, and the specificity is 92.9%. NT-proBNP may be a quantitative indicator of arterial duct shunt; the detection of serum NT-proBNP levels at 3 and 5 days after birth is helpful for early prediction of PDA.


Sleep characteristics and cardiovascular risk in children and adolescents: an enumerative review.
Cardiovascular risk factors develop in childhood and adolescence. This enumerative review addresses whether sleep characteristics, including sleep duration, continuity, quality, and daytime sleepiness, are associated with cardiovascular risk factors in young people. Thirty-nine studies were identified, which examined the following risk factors: metabolic syndrome, glucose and insulin, lipids, blood pressure, and cardiovascular responses to psychological stressors. Due to the availability of other reviews, 16 longitudinal studies of obesity published in 2011 and later were also included in this report. Excluded from the review were studies of participants with suspected or diagnosed sleep disorders and reports from sleep deprivation experiments. Combining studies, evidence was strongest for obesity, followed by glucose, insulin, blood pressure (especially ambulatory blood pressure), and parasympathetic responses to psychological stressors. There was little evidence for metabolic syndrome cluster, lipids, and blood pressure responses to psychological stressors. The more positive associations were obtained for studies that incorporated objective measures of sleep and that included adolescents. The foundational evidence is almost entirely cross-sectional, except for work on obesity. In summary, available evidence suggests that the associations between sleep characteristics and cardiovascular risk vary by risk factor. It is time to conduct studies to determine antecedent and consequent relationships, and to expand risk factors to include markers of inflammation.


Sequential intermediates in the transport of protein between the endoplasmic reticulum and the Golgi.
Semi-intact cells, a cell population in which the plasma membrane is perforated to expose intact intracellular organelles (Beckers, C. J. M., Keller, D. S., and Balch, W. E. (1987) Cell 50, 523-534), efficiently reconstitute vesicular trafficking of protein from the endoplasmic reticulum (ER) to the cis Golgi compartment. We now extend these studies to biochemically dissect transport of protein between the ER and the Golgi into a series of sequential intermediate steps involved in the budding and fusion of carrier vesicles. At least two broad categories of transport intermediates can be detected, those that involve early steps in transport and those involved in late, fusion-related events. Early transport steps require the transport of protein through a novel intermediate compartment in which protein accumulates at reduced temperature (15 degrees C). We demonstrate that both entry and exit from this 15 degrees C compartment can be successfully reconstituted in vitro. A late step in delivery of protein to the cis Golgi compartment requires Ca2+ (pCa7) and is coincident with a step which is sensitive to a peptide analog which blocks interaction between the Rab family of small GTP-binding proteins and a downstream effector protein(s) (Plutner, H., Schwaninger, R., Pind, S., and Balch, W. E. (1990) EMBO J. 9, 2375-2384). The combined results suggest that a single round of vesicular transport between the ER and the Golgi involves a rapid transit through N-ethylmaleimide-sensitive, guanosine 5'-(3-O-thio)triphosphate-sensitive, ATP- and cytosol-dependent step(s) involved in vesicle formation or transport to a novel intermediate compartment, followed by a regulated fusion event triggered in the presence of Ca2+ and functional components interacting with member(s) of the Rab gene family.


Hetero-oligomerization of Rho and Ras GTPases Connects GPCR Activation to mTORC2-AKT Signaling.
The activation of G-protein-coupled receptors (GPCRs) leads to the activation of mTORC2 in cell migration and metabolism. However, the mechanism that links GPCRs to mTORC2 remains unknown. Here, using Dictyostelium cells, we show that GPCR-mediated chemotactic stimulation induces hetero-oligomerization of phosphorylated GDP-bound Rho GTPase and GTP-bound Ras GTPase in directed cell migration. The Rho-Ras hetero-oligomers directly and specifically stimulate mTORC2 activity toward AKT in cells and after biochemical reconstitution using purified proteins in vitro. The Rho-Ras hetero-oligomers do not activate ERK/MAPK, another kinase that functions downstream of GPCRs and Ras. Human KRas4B functionally replace Dictyostelium Ras in mTORC2 activation. In contrast to GDP-Rho, GTP-Rho antagonizes mTORC2-AKT signaling by inhibiting the oligomerization of GDP-Rho with GTP-Ras. These data reveal that GPCR-stimulated hetero-oligomerization of Rho and Ras provides a critical regulatory step that controls mTORC2-AKT signaling.


Safety and efficacy of deferasirox in the management of transfusion-dependent patients with myelodysplastic syndrome and aplastic anaemia: a perspective review.
Deferasirox is an orally administered, once-daily iron chelator with a generally good safety and efficacy profile. Reported adverse events in the older myelodysplastic population are somewhat different to the more intensively investigated and younger thalassaemic population. Renal impairment is the most concerning adverse event, but this is reversible if identified and the drug is withdrawn early. Gastrointestinal effects, particularly diarrhoea, can be troublesome for older patients, but can be minimized with tailored therapy. Negative iron balance can be achieved in most patients with a median dose of 20 mg/kg/day, and doses up to 40 mg/kg are possible in patients with severe iron overload, who are at risk of cardiac decompensation.


Isolation and characterization of major histocompatibility complex class II B genes in cranes.
In this study, we isolated and characterized the major histocompatibility complex (MHC) class II B genes in cranes. Genomic sequences spanning exons 1 to 4 were amplified and determined in 13 crane species and three other species closely related to cranes. In all, 55 unique sequences were identified, and at least two polymorphic MHC class II B loci were found in most species. An analysis of sequence polymorphisms showed the signature of positive selection and recombination. A phylogenetic reconstruction based on exon 2 sequences indicated that trans-species polymorphism has persisted for at least 10 million years, whereas phylogenetic analyses of the sequences flanking exon 2 revealed a pattern of concerted evolution. These results suggest that both balancing selection and recombination play important roles in the crane MHC evolution.


Neurocalcin immunoreactivity in rat olfactory bulb.
Neurocalcin, a newly discovered calcium-binding protein belonging to the recoverin-like superfamily, was detected immunohistochemically in tufted cells from the rat olfactory bulb. More precisely, only periglomerular tufted cells and some tufted cells from the external plexiform layer were expressing neurocalcin. Western blot analysis has confirmed the presence of neurocalcin in rat olfactory bulb. Lack of neurocalcin immunoreactivity in mitral cells and periglomerular cells favor a different phylogenic origin between tufted and mitral or periglomerular cells.


Immediate impairment of left ventricular mechanical performance and force-frequency relation by rate-responsive dual-chamber, but not atrial pacing: Implications from intraventricular isovolumic relaxation flow.
Despite the maintenance of atrioventricular (AV) synchrony, the detrimental effect of left ventricular asynchronization on mechanical performance and intraventricular flow by nonphysiologic right ventricular apical pacing in dual-chamber pacing, with and without rate adaptation, is not clear. Twenty-seven consecutive patients receiving permanent pacemakers for symptomatic bradyarrhythmias (18 with DDD and 9 with AAI mode pacemakers) were evaluated with standard and tissue Doppler echocardiography before and 24 h after pacemaker implantation. The rate-response effect of pacing was studied by programmed rate with increments of 20, from 60 to 100/min. Color M-mode echocardiography demonstrated that much more DDD patients developed new biphasic intraventricular flow during isovolumic relaxation period than AAI patients (13/18 versus 0/9, P<0.001). In DDD patients, the ventricular relaxation represented by mitral annulus velocity in early diastole significantly attenuated (before vs. after DDDR, 8.5+/-2.8 vs. 5.2+/-1.2 cm/s, P<0.05), and also the mitral flow propagation velocity (33+/-11 vs. 25+/-5 cm/s, P<0.01). The myocardial performance index increased after DDD (0.70+/-0.15 vs. 0.79+/-0.24, P<0.05) but not after AAI (0.61+/-0.1 vs. 0.59+/-0.08, P=NS). For both pacing groups, the accelerated pacing rate prolonged the isovolumic relaxation time and shortened the diastole period (P<0.001). However, only DDD patients had a decreased mitral flow propagation velocity (P=0.026) and an attenuated force-frequency relation in programmed rate acceleration. Despite the AV synchrony, right ventricular apical pacing immediately attenuates the left ventricular contraction and relaxation performance, which deteriorated further and suppressed the physiologically positive force-frequency relation after accelerated pacing rate.


Conditioning of aluminium-based water treatment sludge with Fenton's reagent: effectiveness and optimising study to improve dewaterability.
Alternative conditioning of aluminium-based drinking water treatment sludge using Fenton reagent (Fe2+/H2O2) was examined in this study. Focuses were placed on effectiveness and factors to affect such novel application of Fenton process. Experiments have demonstrated that considerable improvement of alum sludge dewaterability evaluated by capillary suction time (CST) can be obtained at the relative low concentrations of Fenton reagent. A Box-Behnken experimental design based on the response surface methodology was applied to evaluate the optimum of the influencing variables, i.e. iron concentration, hydrogen peroxide concentration and pH. The optimal values for Fe2+, H2O2, and pH are 21 mg g(-1)DS(-1)(dry solids), 105 mg g(-1)DS(-1) and 6, respectively, at which the CST reduction efficiency of 48+/-3% can be achieved, this agreed with that predicted by an established polynomial model in this study.


Survivorship: a concept analysis.
Survivorship is a relevant concept to evaluate as technology is allowing people to survive previously terminal conditions. The act of surviving a life-altering event can result in survivorship by altering continuity of identity. This paper analyzes the concept of survivorship through the use of Walker and Avant's model of concept analysis. A comprehensive literature review and bibliographic search resulted in numerous sources available for analysis. The recognition of commonalities among all types of survivors could have important implications for support groups and rehabilitation therapies.


Interdigitating dendritic cell sarcoma: analysis of two original extra-nodal cases and review of literature.
Interdigitating dendritic cell sarcoma (IDCS) is a rare, highly malignant tumor with a poor prognosis, and current knowledge of this tumor is limited. It is reported that lymph nodes are the primary localization sites. However, in recent years, many primary IDCS have also been reported in the extra-nodal sites, which undoubtedly increases the difficulty of diagnosis. There are very few reports that systematically analyze the clinicopathologic features of IDCS. Here we described two cases of extra-nodal IDCS and reviewed the literature of 44 other published cases of extra-nodal IDCS. Thus, the clinical symptoms, pathological diagnosis, and therapeutic effects of 46 cases of extra-nodal IDCS were summarized in detail. Considering the paucity of available data with regard to IDCS, a thorough and detailed summary would help to better diagnose and treat this neoplasm.


Concordance of self- and informant-rated depressive symptoms in nursing home residents with Dementia: cross-sectional findings.
Depression is highly prevalent in nursing home residents living with moderate to severe dementia. However, assessing depressive symptoms in residents with dementia can be challenging and may vary by rater perspective. We aimed to investigate the concordance of, and factors associated with self- and informant-rated depressive symptoms in nursing home residents with dementia. Cross-sectional data was collected from N = 162 nursing home residents with dementia (age: 53-100; 74% women). Self-ratings were assessed with the Geriatric Depression Scale, while the depression and anxiety items of the Neuropsychiatric Inventory were used for informant-ratings. Cohen's Kappa was calculated to determine the concordance of both measures and of each with antidepressant medication. Multivariate associations with sociodemographic variables, self- and informant-rated quality of life, dementia stage, neuropsychiatric symptoms, functional status and antidepressant medication were analysed with linear mixed models and generalized estimating equations. Concordance between self- and single item informant-rated depressive symptoms was minimal (Cohen's Kappa = .22, p = .02). No concordance was found for self-reported depressive symptoms and the combined informant-rated depression-anxiety score. Self-reported depression was negatively associated with self-rated quality of life (β = -.32; 95%CI: -.45 to -.19, p < .001), informant-rated quality of life (β = -.25; 95%CI: -.43 to -.07, p = .005) and functional status (β = -.16; 95%CI: -.32 to -.01, p = .04), whilst single item informant-rated depression revealed negative associations with informant-rated quality of life (β = -.32; 95%CI: -.52 to -.13, p = .001) and dementia stage (β = -.31; 95%CI: -.52 to -.10, p = .004). The combined informant-rated depression-anxiety score showed negative associations with self-rated quality of life (β = -.12; 95%CI: -.22 to -.03, p = .01) and dementia stage (β = -.37; 95%CI: -.67 to -.07, p = .02) and a positive association with neuropsychiatric symptoms (β = .30; 95%CI: .10 to .51, p = .004). No concordance was found with antidepressant medication. In line with our expectations, low agreement and unique association patterns were found for both measures. These findings indicate that both instruments address different aspects of depression und underline the need for comprehensive approaches when it comes to detecting signs of clinically relevant depressive symptoms in dementia. The trial was registered with the ISRCTN registry (Trial registration number: ISRCTN98947160 ).


Management of elderly patients with primary breast cancer.
From 1974 through 1983, three hundred forty-three patients aged 70 years or older at diagnosis received comprehensive post-operative radiation therapy for localized (Stage I-III) breast cancer following surgical procedures ranging from incisional biopsies to classical radical mastectomy. The 5- and 10-year overall survival rates for this series of elderly patients are 67% and 33%. The respective disease-free survival rates are 67% and 42%. Over one-half of these women were treated by less than total mastectomy. No differences were seen in survival, disease-free survival, or local regional control rates comparing similarly staged patients treated by radical mastectomy, modified radical mastectomy, or tylectomy. Complications were few and seen primarily in those patients subjected to axillary dissection prior to irradiation. Long term survival appears to be achievable in the majority of elderly patients with regionally confined disease at presentation and aggressive treatment with curative intent is warranted. These elderly patients are often poor candidates for radical surgery. In this patient population, conservative surgery with post-operative radiation therapy is well tolerated and provides equivalent results to more radical surgical procedures.


Liver regeneration in humans is characterized by significant changes in cellular phosphorus metabolism: assessment using proton-decoupled 31P-magnetic resonance spectroscopic imaging.
In the present study we applied proton-decoupled 31P magnetic resonance spectroscopic imaging (MRSI) to noninvasively assess liver metabolism in patients who had undergone a partial hepatectomy (PH). Proton-decoupled 31P chemical shift imaging was performed in 47 patients 2-28 days following major hepatectomy, and the results were compared with those from eight control subjects. All studies were performed on a 1.5T MR imager (General Electric, Milwaukee, WI) equipped with a stand-alone proton decoupler. A 31P-1H resonator pair was used for data acquisition, and 31P data were obtained in 34 min. Liver regeneration was characterized by increases in phosphoethanolamine (PE), and decreases in nucleoside triphosphates (NTP), glycerophosphoethanolamine (GPE), and glycerophosphocholine (GPC). These alterations were most marked 48-72 hr after hepatectomy and returned to baseline within 3 weeks. The level of PE measured by MRSI was also found to depend on the percentage of liver that was removed, while changes in levels of cellular high energy phosphates were independent of the size of liver resection. Implementation of proton-decoupling was critical for assessing individual phosphomonoester and phosphodiester components. This study demonstrates that 31P MRSI can be used to assess metabolic changes in humans during liver regeneration, and may be useful for assessing derangement of the regenerative process or guiding adjuvant chemotherapies.


Diagnosis of primary lung cancer and benign pulmonary nodules: a comparison of the breath test and 18F-FDG PET-CT.
With the application of low-dose computed tomography in lung cancer screening, pulmonary nodules have become increasingly detected. Accurate discrimination between primary lung cancer and benign nodules poses a significant clinical challenge. This study aimed to investigate the viability of exhaled breath as a diagnostic tool for pulmonary nodules and compare the breath test with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT). Exhaled breath was collected by Tedlar bags and analyzed by high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). A retrospective cohort (n = 100) and a prospective cohort (n = 63) of patients with pulmonary nodules were established. In the validation cohort, the breath test achieved an area under the receiver operating characteristic curve (AUC) of 0.872 (95% CI 0.760-0.983) and a combination of 16 volatile organic compounds achieved an AUC of 0.744 (95% CI 0.7586-0.901). For PET-CT, the SUVmax alone had an AUC of 0.608 (95% CI 0.433-0.784) while after combining with CT image features, 18F-FDG PET-CT had an AUC of 0.821 (95% CI 0.662-0.979). Overall, the study demonstrated the efficacy of a breath test utilizing HPPI-TOFMS for discriminating lung cancer from benign pulmonary nodules. Furthermore, the accuracy achieved by the exhaled breath test was comparable with 18F-FDG PET-CT.


A systematic review of the literature about competence and poor insight.
Formally, incompetence implies that a patient cannot meet the legal requirements for informed consent. Our aim was to review the scientific literature on the relationship between competence and insight in patients with psychiatric disorders, how competence and insight are connected in these patients and whether there are differences in competence and insight among patients with different disorders. A search in PubMed/Medline was performed. Articles were assessed on relevance criteria by two independent reviewers. Study design, population, variables, and outcomes were extracted. Seven articles were included on studies of psychiatric inpatients and outpatients and of psychotic and non-psychotic patients. All studies used the MacArthur Competence Assessment Tool (MacCAT). All studies but one found a strong correlation between poor insight and incompetence. Psychotic patients with poor insight are very likely to be incompetent, and psychotic patients with adequate insight are generally competent. One well-executed study showed that in non-psychotic disorders, however, another relationship emerges; competence and insight do not completely overlap in these patients. Most incompetent psychotic patients have poor insight, but non-psychotic patients with adequate insight were incompetent in a substantial number of cases. In sum: non-psychotic patients with adequate insight can be incompetent.


Relations between immunological and neurological memory: learning ability in rats during immunostimulation.
The effect of an immunostimulator, Freund's complete adjuvant (FCA), on the ability of Wistar rats to learn in a visual discrimination test was studied by foodgetting and electric-shock avoidance methods. A significant improvement in learning ability was demonstrated under the influence of FCA when the negative reinforcement method was used, but a worsening when the positive reinforcement method was used. Analysis of the dynamics of extinction of the reflexes formed gave similar results. The possible relations between immunogenesis and memory forming processes are discussed.


Essential tremor: differential diagnosis and current therapy.
Essential tremor is a common movement disorder that affects between 5 and 10 million persons in the United States. It is characterized primarily by an action and postural tremor most often affecting the arms, but it can also affect other body parts. Essential tremor is a progressive neurologic disorder and can cause substantial disability in some patients. Although there is no cure for essential tremor, pharmacologic and surgical treatments can provide some benefit. Primidone and propranolol are first-line treatments. Other medications with potential efficacy include benzodiazepines, gabapentin, topiramate, and botulinum toxin. Patients with medication-resistant tremor may benefit from thalamotomy or deep brain stimulation of the thalamus. The use of medical and surgical therapies can provide benefit in up to 80% of patients with essential tremor.


The human sperm-hamster egg penetration assay: prognostic value.
Males from 227 infertile couples were evaluated using the human sperm-hamster egg penetration assay (SPA). Indications for the SPA were abnormal semen analyses, poor postcoital tests, documented autologous sperm antibodies, and long-term unexplained infertility. Normal results defined as greater than or equal to 11% penetration were seen in 58.6% of couples. Penetration rates of 1% to 10% were observed in 25.6%, and 15.9% failed to penetrate any of the oocytes. During the follow-up period, with a mean of 17.9 months, 26.9% conceived at least once with or without treatment. Monthly fecundity was 0.014 for normal SPA patients and 0.007 for the abnormal SPA group when calculated by the Kaplan-Meier survival curve with Cox correction for unequal follow-up. The monthly fecundity rate at any time during the 30-month interval of follow-up was twice as great for men with normal SPA values as for those with abnormal values, regardless of male or female diagnosis or therapy indicating the prognostic value of the SPA in an infertile population.


Ciliary neurotrophic factor stimulates tyrosine hydroxylase activity.
Tyrosine hydroxylase (TH) is the rate-limiting enzyme in norepinephrine synthesis, and its expression and activity are regulated by many factors in sympathetic neurons. Cytokines that act through gp130, such as ciliary neurotrophic factor (CNTF) decrease norepinephrine production in sympathetic neurons by suppressing TH mRNA and stimulating degradation of TH protein, leading to the loss of enzyme. Their effect on the activity of TH is unclear, but recent in vivo observations suggest that cytokines may stimulate TH activity. We investigated this issue by quantifying TH protein levels and activity in cultured sympathetic neurons. We also examined the state of TH phosphorylation on serine 31 and 40, sites known to affect TH activity and degradation. We found that CNTF, acting through gp130, stimulated the rate of l-3,4-dihydroxyphenylalanine production while at the same time decreasing TH enzyme levels, thereby increasing the specific activity of the enzyme. We also found that phosphorylation of TH on Ser31 was increased, and phosphorylation on Ser40 was decreased, after four days of CNTF exposure. Our data are consistent with previous findings that Ser31 phosphorylation stimulates TH activity, whereas Ser40 phosphorylation can target TH for proteasomal degradation.


Prognosis of patients with bilateral macular drusen.
Of 71 patients with only bilateral macular drusen, 8 eyes in 7 patients (9.9%) developed exudative maculopathy over an average follow-up of 4.3 years (14.5% cumulative risk). Severe visual loss due to exudative maculopathy occurred in 7 eyes of 6 patients (8.5%) for a 5-year cumulative risk of 12.7%. Features of the drusen were analyzed, but only the association with focal hyperpigmentation (P less than 0.001) and more than minimal drusen confluence (P less than 0.05) were statistically significant. Older patients had more severe drusen. Photostress test delay did not correlate with visual acuity, age, or severity of drusen.


Latissimus dorsi perforator flap.
Although exact information on the distribution of reliable perforators has not been published, its underlying reproducible pattern may be experienced with clinical trials. The LD perforator flap is a typical example of thin perforator flap and it can be used widely as a resurfacing tool or reconstructive modality with various composition. Through clinical experience it was validated that a single reliable perforator is sufficient for perfusion of the entire flap. Finally, the perforator concept gives the surgeon the freedom to select, tailor, or compose the flap independently from the limited indications of the conventional flaps, according to the donor or pedicle problems. With increasing use of the perforator flap, the conventional flap can be expanded to its ultimate potential with more reliability.


Surface properties of poly(N-monoalkylmaleamic acid-alt-styrene) sodium salts: effect of the molecular weight and the side chain length.
The surface properties of poly(N-monoalkylmaleamic acid-alt-styrene) sodium salts are studied as a function of the molecular weight and the size of the linear alkyl lateral chain of the polyelectrolyte. The experimental results are well described by the Gibbs-Szyszkowski treatment. Both the surface tension behavior and the standard free energy of adsorption depend on the polyelectrolyte side chain and on the average molecular weight, M(w). An M(w)-dependent contribution to the free energy of adsorption ranging from -1.21 to -1.05 kJ for mole of methylene groups is found. The area covered by monomer units increases with M(w) and the sizes of side chains are similar to those reported in small-molecule systems. The nature of the functional group amide in the side chain has practically no effect on the surface properties as compared with the ester group in this kind of polyelectrolytes.


Transient appearance of amyloid precursor protein plaques in the brain of thymectomized rats after human leptomeningeal cell grafts.
Cells cultured from Alzheimer disease leptomeninges or skin were grafted into the cortex of adult thymectomized rats. At 3 days post-implant, plaque-like aggregates were found in the cortex, corpus callosum, septum and caudate nucleus. These structures were immunopositive for human amyloid precursor protein (APP), human amyloid beta peptide (Abeta), cathepsin D, apolipoprotein E and ubiquitin. Aberrant tau+ neurites, reactive astrocytes and microglia were associated with many aggregates. Although birefringent amyloid occupied the central area of most aggregates, these structures had disappeared by l month post-implant. Abeta and APP produced by grafted non-neural human cells can penetrate rat brain and form plaque-like structures, which can be effectively cleared by the rat.


Cue reactivity in dependent amphetamine users: can monistic conditioning theories advance our understanding of reactivity?
Forty-eight dependent injecting amphetamine users (AUs) and 48 controls were exposed to an amphetamine-related video and three affective control videos, and their amphetamine-related responses (amphetamine symptoms, withdrawal symptoms, and for AUs, "positive" and "negative" craving, based on the desire for positive and negative reinforcement, respectively) were recorded after each one. Both groups responded to the amphetamine video with increased withdrawal symptoms relative to control videos, suggesting that drug-related cues have significant unconditioned aversive properties. Between-group differences in amphetamine symptoms were evident only after the amphetamine video, supporting a conditioned drug agonistic model of cue reactivity. Among AUs, both positive and negative craving increased significantly after the amphetamine video, providing prima facie evidence for both conditioned withdrawal and conditioned drug agonistic accounts of cue reactivity. However, the lack of consistent and strong correlations between the two types of craving and the affective states hypothesized to induce such craving cannot be accommodated by the dominant models of the role of conditioning in maintaining addictive behaviours. This suggests a need to build upon theories of cue reactivity which predict conditioned responses to be either drug-like or drug-opposite.


COVID-19 face masks attracted Cellulomonas and Acinetobacter bacteria and provided breeding haven for red cotton bug (Dysdercus suturellus) and house cricket (Acheta domesticus).
This study investigated the possibility of COVID-19 medical face masks to affect bacterial and macrofaunal communities in open soil environment. An estimated 1.24 trillion of face masks have been used and discarded as a result of the COVID-19 pandemic, with a significant part of this ending up in the soil environment, where they degrade gradually over time. Because bacteria and macrofauna are sensitive indicators of changes in soil ecosystem, we investigated possible impacts of face masks on population, distribution, and diversity of these soil species. Effect on soil bacterial community was studied by both culture-based and advanced molecular (metagenomics) approach, while impact on macrofauna was investigated by examining monoliths around heap of masks for soil insects. In both cases, control soil experiments without face masks were also set up and monitored over a period of 48 weeks. The study found that the presence of face masks led to a more diverse bacterial community, although no influence on overall bacterial population was evidenced. More importantly, bacteria belonging to the genera Cellulomonas and Acinetobacter were found prominently around face masks and are believed to be involved in biodegradation of the masks. The bacterial community around the masks was dominated by Proteobacteria (29.7-38.7%), but the diversity of species increased gradually with time. Tiny black ants (Monomorium invidium) were attracted to the face masks to take advantage of water retained by the masks during the period of little rainfall. The heaps of face masks also provided shelter and breeding "haven" for soil insects, notably the red cotton bug (Dysdercus suturellus) and house cricket (Acheta domesticus), thereby impacting positively on the population of insect species in the environment. This study provides insights into the actual impacts of face masks on soil organisms under normal outdoor environmental conditions.


Correlates for psycho-active substance use among boarding secondary school adolescents in Enugu, South East, Nigeria.
Psycho-active substance use among adolescents is a national and global problem and its attendant effects on adolescents cannot be overemphasized. The objectives of this study are to determine the prevalence and pattern of psychoactive substance use among adolescents; the substances involved and the extent of the problem in this locale. This is a cross-sectional study that assesses the pattern of psychoactive substance use among secondary school adolescents in Enugu, south East, Nigeria. The study was carried out among adolescents attending six secondary boarding schools in Enugu metropolis of Enugu State of Nigeria. The WHO Student Drug Use Questionnaire was adapted for this study. Data were analyzed using the Statistical Package for Social Sciences program (SPSS), version 17. Chi-square and multivariate regression were used as a test of significance for qualitative variables. A p-value less than 0.05 were accepted as significant for each statistical test. Out of 900, a total of 896 respondents, comprising 400 and 82 boys (482) (53.8 %) and 400 and 14 girls (414) (46.2 %) completed the questionnaires. This gave a response rate of 99.6 %. The study revealed that the prevalence of current use for psychoactive substances ranges from 0.4 to 34.9 % while that for life use ranges from 0.8 to 63.5 %. The least being cannabis and the most being kola nuts. Kola nut is the most widely used psychoactive substance both for current use, past year use and the respondents' life time use. It shows a lifetime prevalence of 63.5 % and a current use prevalence of 34.9 %. More than half of the users of each of the psychoactive substances take it occasionally, using them on 1-5 days in a month. On the other hand, almost one-quarter of the users of each of the substances take it on 20 or more days in a month. The study revealed that the prevalence of current use for psychoactive substances ranges from 0.4 to 34.9 % while that for life use ranges from 0.8 to 63.5 %. The least being cannabis and the most being kola nuts.


DNA Charge Transport: from Chemical Principles to the Cell.
The DNA double helix has captured the imagination of many, bringing it to the forefront of biological research. DNA has unique features that extend our interest into areas of chemistry, physics, material science, and engineering. Our laboratory has focused on studies of DNA charge transport (CT), wherein charges can efficiently travel long molecular distances through the DNA helix while maintaining an exquisite sensitivity to base pair π-stacking. Because DNA CT chemistry reports on the integrity of the DNA duplex, this property may be exploited to develop electrochemical devices to detect DNA lesions and DNA-binding proteins. Furthermore, studies now indicate that DNA CT may also be used in the cell by, for example, DNA repair proteins, as a cellular diagnostic, in order to scan the genome to localize efficiently to damage sites. In this review, we describe this evolution of DNA CT chemistry from the discovery of fundamental chemical principles to applications in diagnostic strategies and possible roles in biology.


Clinical and angiographic outcomes in patients with intracranial aneurysms treated with the pipeline embolization device: intra-procedural technical difficulties, major morbidity, and neurological mortality decrease significantly with increased operator experience in device deployment and patient management.
Flow diversion constitutes a pivotal advancement in endovascular intracranial aneurysm treatment, but requires development of a new skill set. The aim of this study is to determine whether outcomes after treatment with the Pipeline Embolization Device improve with experience. We retrospectively reviewed all patients with intracranial aneurysms treated with Pipeline at two centers over a 4.5-year period. Baseline patient and aneurysm characteristics, complications, and angiographic outcomes were analyzed. One hundred forty patients underwent 150 Pipeline procedures to treat 167 intracranial aneurysms during the study period, 109 women, mean age 55.4 years. One hundred twenty-six aneurysms were ICA, mean size 10.2 mm and mean neck 6.4 mm. Intra-procedural technical difficulties were higher during the first 75 procedures compared with the subsequent 75 (13.3 vs 2.7%; p = 0.03), as combined major morbidity and neurological mortality (14.7 vs 4%; p = 0.046). In multivariate regression analysis, increased operator experience with Pipeline remained an independent predictor of intra-procedural technical difficulties (p = 0.02, odds ratio (OR) 0.015, 95% CI 0.0004-0.55) and combined major morbidity and neurological mortality (p = 0.03, OR 0.16, 95% CI 0.03-0.84). At last follow-up, 123 aneurysms were completely occluded (81.5%, mean 24 months). In our cohort, age ≤ 53 years was an independent predictor of complete aneurysm occlusion at last follow-up (p = 0.001, OR 0.92, 95% CI 0.88-0.97). Five aneurysms were retreated (3.3%). The Pipeline embolization device is an effective treatment for intracranial aneurysms. The risk of intra-procedural technical difficulties and combined major morbidity and neurological mortality decreases significantly with increased operator experience in Pipeline deployment and patient management.


Towards automation of the polyol process for the synthesis of silver nanoparticles.
Metal nanoparticles have a substantial impact across different fields of science, such as photochemistry, energy conversion, and medicine. Among the commonly used nanoparticles, silver nanoparticles are of special interest due to their antibacterial properties and applications in sensing and catalysis. However, many of the methods used to synthesize silver nanoparticles often do not result in well-defined products, the main obstacles being high polydispersity or a lack of particle size tunability. We describe an automated approach to on-demand synthesis of adjustable particles with mean radii of 3 and 5 nm using the polyol route. The polyol process is a promising route for silver nanoparticles e.g., to be used as reference materials. We characterised the as-synthesized nanoparticles using small-angle X-ray scattering, dynamic light scattering and further methods, showing that automated synthesis can yield colloids with reproducible and tuneable properties.


Prolonged local expression of anti-CD4 antibody by adenovirally transduced allografts can promote long-term graft survival.
Currently, successful transplantation of allografts requires the systemic use of immunosuppressive drugs. These can cause serious morbidity due to toxicity and increased susceptibility to cancer and infections. Local production of immunosuppressive molecules limited to the graft site would reduce the need for conventional, generalized immunosuppressive therapies and thus educe fewer side effects. This is particularly salient in a disease like type 1 diabetes, which is not immediately life-threatening yet islet allografts can effect a cure. We studied the efficacy of locally produced anti-CD4 antibody, mediated by adenovirus (Adv-anti-CD4) transduction of islets, to enhance allograft survival. Adenovirus-transduced islets were transplanted under the kidney capsule of diabetic recipients and graft rejection determined by monitoring blood glucose levels. Adv-anti-CD4 transduction of mouse islets afforded protection against allogeneic rejection after transplantation into fully mismatched recipients. In some recipients, the islet allograft survival was prolonged (persisting for at least 15 weeks), corresponding to the prolonged expression of the anti-CD4 antibody. The effect was local, as absence of CD4+ T lymphocytes was observed primarily at the graft site. Immunosuppressive effects can be restricted locally by our strategy. Local production of a single antibody against one subset of T lymphocytes can protect mouse islets from allograft rejection during transplantation to treat diabetes. Our findings foreshadow that this strategy may be even more effective when a combination of antibodies are used and that similar strategies may prevent xenograft rejection.


Controversies in Traditional Oral and Maxillofacial Reconstruction.
Traditional reconstruction of the head and neck and significantly evolved over the last 20 to 30 years with advances in microvascular surgery, biologic materials such as bone morphogenic protein, and dental implant predictability. Earlier and more definitive reconstruction can now be achieved with combining therapies, allowing patients immediate restoration of function and improved cosmetics. Antiresorptive medications, such as Denosumab and bisphosphonates, have complicated bony reconstruction treatments with altered biology and less-predictable results. Virtual surgical planning is a major advancement for reconstruction pretreatment planning and designing of intraoperative tools to expedite the operation and achieve more predictable results.


[Neutrophil chemotaxis in patients with infectious-allergic bronchial asthma].
Patients with infectious allergic bronchial asthma have been shown to have a defect in the chemotaxis of neutrophils. This defect is more pronounced in corticosteroid-dependent patients.


Interleukin-10 promoter microsatellite polymorphisms influence the immune response to heparin and the risk of heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) results from an atypical immune response with synthesis of IgG antibodies (Abs) to platelet factor 4/heparin complexes (PF4/H), and probably involves both B and T cells. We investigated whether 3 single nucleotide polymorphisms (SNPs), rs1800896 (-1082G/A), rs1800871 (-819C/T) and rs1800872 (-592C/A) and the polymorphic CA repeat microsatellites IL10R [5325CA(11_15)] and IL10G [8134CA(14_29)] are associated with the synthesis of Abs to PF4/heparin and HIT. Eighty-two patients with definite HIT and two control groups were studied. The first control group (Ab(neg)) consisted of 85 patients without Abs to PF4/heparin after cardiopulmonary bypass (CPB). The second control group (Ab(pos)) consisted of 84 patients who had developed significant levels of PF4-specific antibodies after CPB, but without HIT. Allele frequencies of the 3 SNPs were similar in HIT patients and controls. Fourteen alleles in IL10G (G16 to G29) and 3 alleles in IL10R (R13 to R15) were defined. The short G20 allele of IL10G was more frequent in Ab(neg) patients (8.2%) than in Ab(pos) (2.9%) and HIT patients (3%). It thereby appeared to protect against developing Abs to PF4/heparin (OR 0.29; 95% CI [0.12-0.70], p=0.006). Combined haplotypes cH1/cH8 comprising the short G20 + R13 alleles were less frequent in HIT (OR 0.33; 95% CI [0.11-0.97], p=0.036), and levels of Abs to PF4 in Ab(pos) patients were lower in cH1/cH8 subjects (p=0.019). These results suggest that IL10 promoter microsatellite polymorphisms might influence the immune response against PF4/heparin and the risk of HIT.


Occurrence of Su in a German family.
Investigating a paternity case we observed a pretended opposite homozygosity of the S and s alleles between a mother and her child. The presence of the rare allele Su in this family could be demonstrated with the aid of dosage studies and blood group testing of the mother's parents. 22 additional genetic marker systems, including the HLA-system were examined, a biostatistical calculation was performed as well. The results obtained from these testings were in accordance with the hereditary rules and the posssibility of ilegitimacy or of children's substitution could be excluded. Only Caucasoid ancestry was known to the family. In addition, family members showed another rare blood group marker, the allele GPT0.


Supervised discriminant analysis for droplet micro-magnetofluidics.
We apply the technique of supervised discriminant analysis (SDA) for in-flow detection in droplet-based magnetofluidics. Based on the SDA, we successfully discriminate bivariant droplets of different volumes containing different encapsulated magnetic content produced by a GMR-based lab-on-chip platform. We demonstrate that the accuracy of discrimination is superior when the correlation of variables for data training is included to the case when the spatial distribution of variables is considered. Droplets produced with differences in ferrofluid concentration of 2.5 mg/ml and volume of 200 pl have been identified with high accuracy (98 %), indicating the significance of SDA for e.g. the discrimination in magnetic immuno-agglutination assays. Furthermore, the results open the way for the development of a unique magnetofluidic platform for future applications in multiplexed droplet-based barcoding assays and screening.


Elevation of serum aluminum in humans on a two-day sucralfate regimen.
Serum aluminum concentrations were determined in ten healthy subjects treated with phenytoin 500 mg and with sucralfate and phenytoin in a crossover fashion. Each subject received four 1,000-mg sucralfate tablets between 8 AM and 10 PM one day before the study, and this was repeated during the study day. A total of eight doses of sucralfate was administered over the two-day period. Serum samples were drawn at 0, 2, 4, 8, 12, 24, 32, and 48 hours after administration. The areas under the serum aluminum concentration-time curves before and after sucralfate (mean +/- SD) were 496.0 +/- 80.9 and 770.9 +/- 146.6 hr-ng/mL, respectively. This increase is statistically significant (P less than .01), indicating that serum aluminum levels are elevated even after two days of treatment with sucralfate. The results from this study are not in agreement with the only other report on this subject.


Changes of hormonal status in young mice by restricted caloric diet. Relation to lifespan extension. Preliminary results.
The maintainance of mice on a reduced caloric diet for 6 weeks starting from weaning time produces persistent changes in their hormonal status as reflected by differences in blood levels of gonadal and adrenal steroids. The changes might express a permanently different hypothalamic regulation. This might account for a prolongation of their life span.


[Behind the scenes of the didactic of nursing science knowledge: role play simulation filmed for learning through "problematic situations"].
clinical simulation to teach expertise to nursing students plays an important role in nursing schools (IFSI). as recommended in the training frame of reference, students must develop skills from real situations. The objective of this study was to determine the importance of role play simulation of 'problematic situations' to boost the process of appropriation of nursing science knowledge and initiate the task of conceptualization among first year students when putting up a drip. this contextual research used qualitative data collected from students who answered three open post-simulation questions in order to communicate how they felt faced with this learning technique. This data was compared with that of two executive tutors who used an observation grid during the simulation. the students' answers have shown that this learning technique offered the possibility to develop dexterity in problem solving skills, to construct new knowledge and to memorize knowledge gained from university science and nursing care. The executive tutors have observed the construction of a meta-cognitive attitude suited to the conceptualization of action. during a change in the relationship with knowledge, the executive tutors noted that students are happy to learn different types of knowledge.


Multiple primary synchronous malignant tumors.
Patients with primary multiple malignancies are progressively increasing due to prolonged survival of cancer patients and to the advances in diagnostic techniques and therapeutic options. Here we present a 66 year-old caucasian patient with four synchronous primary malignant tumors affecting the lung, oropharynx, large bowel and prostate gland, respectively, treated with multidisciplinary approach. The increased incidence of multiple malignant tumors is a real challenge to the clinician and clinical attention should be made to avoid a misdiagnosis. In addition an early diagnosis is essential to achieve a radical treatment. We believe that the treatment modality should be carefully made and tailored on the individual patient suffering from this disease.


Molecular breakpoints of t(11;14)(q13;q32) in multiple myeloma.
We found a t(11;14)(q13;q32) translocation in six patients with multiple myeloma (MM) or plasma cell leukemia. In five of them, rearrangements of BCL1 and PRAD1 could be studied. Two patients showed a rearrangement only with the Prad1 probe, located 120 kb telomeric of the major translocation cluster. The three other patients lacked rearrangements with both Bcl1 and Prad1.


The role of inflammatory chemokines in lymphoid neoorganogenesis in breast cancer.
The expression profiling analysis of inflammatory chemokines and their receptors in newly formed lymph nodes in breast cancer was carried out. The analysis revealed the increase in expression of the genes CCL16, XCR1, CYFIP2, TNFSF14 and the reduction in expression of chemokine ligands CXCL5 and CXCL12 in tertiary lymphoid organs. The obtained results allow us to suggest that the process of induction of lymph nodes neogenesis is identical (in its key mechanisms) to the process of lymphoid tissue neogenesis in autoimmune diseases and in some infections, but may have different triggers.


Martial arts enhances working memory and attention in school-aged children: A functional near-infrared spectroscopy study.
Interventions can improve working memory and attention in school-aged children, but little is known about how regional changes in brain activity promoted by exercise mediate this cognitive improvement. This study focused on the improved neurocognitive functions and intrinsic regional variation within the brain by comparing school-aged children in a martial arts group with those in free-play and rest groups. With a pretest-posttest design, the d2 attention test and N-back tasks were carried out. Functional near-infrared spectroscopy was performed during the pre- and post-intervention N-back tasks and rest. Following the intervention, the d2 attention in all groups remarkably increased, and the attention level of the martial arts group was substantially higher than those of the other two groups. Free-play and martial arts shortened the 1- and 2-back task reaction time and increased the 2-back accuracy rate (AR), and the martial arts group exhibited a significantly higher AR than the other two groups. In addition, the martial arts group showed higher activations in the right orbitofrontal cortex and right Broca's area (r-BA) regions post-intervention 1-back tasks, whereas a strong correlation was observed between 1-back performance and the related brain region. However, under the 2-back task, although the cognitive control was improved, the martial arts group decreased activation in the left frontopolar area and free play decreased the activation in the r-BA and right somatosensory cortex. Together, our findings showed that martial arts could be more conducive to cognitive improvement than physical exercise that requires no cognitive skills and that performing interventions in the earlier stages of childhood may improve the regulation of neural networks involved in cognitive control.