"Campus Craft": A Game for Sexual Assault Prevention in Universities.
Sexual assault is prevalent among college students. In response, universities have implemented prevention education initiatives. These interventions, however, often ignore the broader sociocultural context in which sexual violence occurs. This calls for innovative approaches in prevention education, which address the broader context. Computer games provide such an opportunity by providing simulated real-life scenarios, nonlinear narratives, and an interactive medium. We report the development and pilot testing of "Campus Craft," a game prototype that focuses, among other things, on sexual assault prevention. The prototype was developed through a participatory design process; students, educators, and subject matter experts helped design and develop scenarios, game mechanics, and learning objectives. The prototype was evaluated by college students (n=141) in a multi-method approach. The evaluation encompassed issues of usability, game mechanics, attitudes, and learning outcomes. Findings indicated that participants rated various aspects of the game positively. Additionally, use of "Campus Craft" contributed to differences in student learning of prevention concepts between the pre- and post-test such that students scored higher on the post-test. Findings demonstrate that, on average, students learned several core concepts related to sexual consent and rape culture through gameplay. Results suggest that computer-based gaming may be a viable avenue for sexual assault prevention education. Findings demonstrate that this approach could be effective in increasing student knowledge and understanding of factors that contribute to sexual assault in college. Future research is needed to corroborate findings and better understand the feasibility of using this approach among larger samples of college students.


Interstitial nephritis and high titers of PR3-ANCA: an unusual manifestation of ANCA-associated disease.
We present the case of a 75-year-old female with weight loss, anemia, systemic signs of inflammation, mild renal insufficiency, microscopic hematuria, mixed glomerular and tubular proteinuria, and high titers of PR3-ANCA. Renal biopsy demonstrated interstitial nephritis with some sclerosed but otherwise normal glomeruli. Extensive work-up showed no signs of granulomatous inflammation or other vasculitic organ involvement. We presumed this to be a rare renal manifestation of ANCA-associated disease with the presence of sclerosed glomeruli suggesting a previous history of glomerular involvement. In view of the absence of active vasculitic or granulomatous disease, treatment was limited to low-dose corticosteroids with good response.


Unravelling high density lipoprotein-apolipoprotein metabolism in human mutants and animal models.
Apolipoprotein A-I plays an essential structural and functional role in HDL metabolism and apolipoprotein A-II has important effects on HDL metabolism and function. Kinetic studies in humans have established that variation in plasma HDL-cholesterol and apolipoprotein A-I concentrations is primarily determined by variation in the rate of apolipoprotein A-I catabolism. In contrast, plasma apolipoprotein A-II levels are primarily determined by the rate of apolipoprotein A-II production. Genetic factors play an important role in modulating the plasma levels of HDL-cholesterol and apolipoproteins A-I and A-II. Studies in humans have established that mutations in genes encoding enzymes that esterify cholesterol (lecithin : cholesterol acyltransferase), transfer cholesterol (cholesteryl ester transfer protein) and hydrolyze lipids (hepatic lipase, lipoprotein lipase) regulate HDL-cholesterol and apolipoprotein A-I levels by modifying the lipid content (and therefore the size) of HDL particles. Recent studies in transgenic and knockout animals have confirmed the key role of HDL lipid-modifying proteins in HDL, apolipoprotein A-I and apolipoprotein A-II metabolism and have expanded our understanding of the role of lipid modification in determining plasma concentrations of HDL-cholesterol and apolipoprotein A-I, as well as the potential functional roles of apolipoprotein A-II.


Contact dermatitis in older adults: a review of the literature.
Contact dermatitis is a significant health problem affecting the elderly. Impaired epidermal barrier function and delayed cutaneous recovery after insult enhances susceptibility to both irritants and allergens. Exposure to more numerous potential sensitizers and for greater durations influences the rate of allergic contact dermatitis in this population. Medical co-morbidities, including stasis dermatitis and venous ulcerations, further exacerbate this clinical picture. However, while these factors tend to increase the degree of sensitization in the elderly, waning immunity can actually decrease such a propensity. This interplay of both intrinsic and extrinsic factors makes a generalization on trends for contact dermatitis in older adults challenging. The literature has varying reports on the overall incidence of allergic contact dermatitis with advancing age. Nevertheless, it does clearly show that sensitivity to topical medicaments increases with age. Irritant contact dermatitis studies are more consistent, with less reactivity (to irritants) in older compared with younger skin. Diagnosis of both irritant and allergic contact dermatitis is based on a thorough history, complete skin examination, and comprehensive patch testing. The mainstay of therapy is avoidance of the offending chemical substances and the use of topical along with systemic therapies, depending on the severity of the condition.


Exposure to Different Types of Violence and Subsequent Sexual Risk Behavior among Female STD Clinic Patients: A Latent Class Analysis.
Diverse forms of violence, including childhood maltreatment (CM), intimate partner violence (IPV), and exposure to community violence (ECV), have been linked separately with sexual risk behaviors. However, few studies have explored multiple experiences of violence simultaneously in relation to sexual risk-taking, especially in women who are most vulnerable to violent experiences. Participants were 481 women (66% African American, Mage = 27 years) attending a publicly-funded STD clinic who reported on their past and current experiences with violence and their current sexual risk behavior. We identified patterns of experience with violence using latent class analysis (LCA) and investigated which combinations of experiences were associated with the riskiest sexual outcomes. Four classes of women with different experiences of violence were identified: Low Violence (39%), Predominantly ECV (20%), Predominantly CM (23%), and Multiply Victimized (18%). Women in the Multiply Victimized and Predominantly ECV classes reported the highest levels of sexual risk behavior, including more lifetime sexual partners and a greater likelihood of receiving STD treatment and using substances before sex. Women with different patterns of violent experiences differed in their sexual risk behavior. Interventions to reduce sexual risk should address violence against women, focusing on experiences with multiple types of violence and experiences specifically with ECV. Additional research is needed to determine the best ways to address violence in sexual risk reduction interventions.


Effect of the Surface Hydrophobicity Degree on the In Vitro Release of Polar and Non-Polar Drugs from Polyelectrolyte Matrix Tablets.
This work is the continuation of a series of studies focused on establishing the relationship between the surface thermodynamic properties of polyelectrolyte matrix tablets and drug release mechanisms. In this case, two model drugs with different polarity features, such as carbamazepine (non-polar) and metoprolol succinate (polar) were used in combination with polymeric material hydroxypropyl-methyl cellulose (HPMC) and two polyelectrolytes derived from maleic anhydride corresponding to the sodium salts of poly(maleic acid-alt-ethylene) and poly(maleic acid-alt-octadecene) named PAM-0Na and PAM-18Na, respectively. The polymers were obtained and characterized as reported previously. Surface studies were performed by the sessile drop method, whilst the surface free energy was determined through Owens, Wendt, Rable and Kaeble (OWRK) semi-empirical model. By contrast, the drug release studies were performed by in vitro dissolution tests, where data were analyzed through dissolution efficiency. The results showed that, depending on the drug polarity, type and polymer proportion, surface properties and drug release processes are significantly affected.


Kinetic controls on the complexation between mercury and dissolved organic matter in a contaminated environment.
The interaction of mercury (Hg) with dissolved natural organic matter (NOM) under equilibrium conditions is the focus of many studies but the kinetic controls on Hg-NOM complexation in aquatic systems have often been overlooked. We examined the rates of Hg-NOM complexation both in a contaminated Upper East Fork Poplar Creek (UEFPC) in Oak Ridge, Tennessee, and in controlled laboratory experiments using reducible Hg (Hg(R)) measurements and C(18) solid phase extraction techniques. Of the filterable Hg at the headwaters of UEFPC, >90% was present as Hg(R) and this fraction decreased downstream but remained >29% of the filterable Hg at all sites. The presence of higher Hg(R) concentrations than would be predicted under equilibrium conditions in UEFPC and in experiments with a NOM isolate suggests that kinetic reactions are controlling the complexation between Hg and NOM. The slow formation of Hg-NOM complexes is attributed to competitive ligand exchange among various moieties and functional groups in NOM with a range of binding strengths and configurations. This study demonstrates the need to consider the effects of Hg-NOM complexation kinetics on processes such as Hg methylation and solid phase partitioning.


Transmission of classical swine fever virus within herds during the 1997-1998 epidemic in The Netherlands.
In this paper, we describe the transmission of Classical Swine Fever virus (CSF virus) within herds during the 1997-1998 epidemic in The Netherlands. In seven herds where the infection started among individually housed breeding stock, all breeding pigs had been tested for antibodies to CSF virus shortly before depopulation. Based upon these data, the transmission of CSF virus between pigs was described as exponential growth in time with a parameter r, that was estimated at 0.108 (95% confidence interval (95% CI) 0.060-0.156). The accompanying per-generation transmission (expressed as the basic reproduction ratio, R0) was estimated at 2.9. Based upon this characterisation, a calculation method was derived with which serological findings at depopulation can be used to calculate the period in which the virus was with a certain probability introduced into that breeding stock. This model was used to estimate the period when the virus had been introduced into 34 herds where the infection started in the breeding section. Of these herds, only a single contact with a herd previously infected had been traced. However, in contrast with the seven previously mentioned herds, only a sample of the breeding pigs had been tested before depopulation (as was the common procedure during the epidemic). The observed number of days between the single contact with an infected herd and the day of sampling of these 34 herds fitted well in the model. Thus, we concluded that the model and transmission parameter was in agreement with the transmission between breeding pigs in these herds. Because of the limited sample size and because it was usually unknown in which specific pen the infection started, we were unable to estimate transmission parameters for weaned piglets and finishing pigs from the data collected during the epidemic. However, from the results of controlled experiments in which R0 was estimated as 81 between weaned piglets and 14 between heavy finishing pigs (Laevens et al., 1998a. Vet. Quart. 20, 41-45; Laevens et al., 1999. Ph.D. Thesis), we constructed a simple model to describe the transmission of CSF virus in compartments (rooms) housing finishing pigs and weaned piglets. From the number of pens per compartment, the number of pigs per pen, the numbers of pigs tested for antibodies to CSF virus and the distribution of the seropositive pigs in the compartment, this model gives again a period in which the virus most probably entered the herd. Using the findings in 41 herds where the infection started in the section of the finishers or weaned piglets of the age of 8 weeks or older, and of which only a single contact with a herd previously infected was known, there was no reason to reject the model. Thus, we concluded that the transmission between weaned piglets and finishing pigs during the epidemic was not significantly different from the transmission observed in the experiments.


Decentralized Adaptive Command Filtered Neural Tracking Control of Large-Scale Nonlinear Systems: An Almost Fast Finite-Time Framework.
In this article, a decentralized adaptive finite-time tracking control scheme is proposed for a class of nonstrict feedback large-scale nonlinear interconnected systems with disturbances. First, a practical almost fast finite-time stability framework is established for a general nonlinear system, which is then applied to the design of the large-scale system under consideration. By fusing command filter technique and adaptive neural control and introducing two smooth functions, the "singular" and "explosion of complex" problems in the backstepping procedure are circumvented, while the obstacles caused by unknown interconnections are overcome. Moreover, according to the framework of practical almost fast finite-time stability, it is shown that all the closed-loop signals of the large-scale system are almost fast finite-time bounded, and the tracking errors can converge to arbitrarily small residual sets predefined in an almost fast finite time. Finally, a simulation example is presented to demonstrate the effectiveness of the proposed finite-time decentralized control scheme.


Use of fluorescence energy transfer to characterize the compactness of the constant fragment of an immunoglobulin light chain in the early stage of folding.
The CL fragment of a type-kappa immunoglobulin light chain in which the C-terminal cysteine residue was modified with N-(iodoacetyl)-N'-(5-sulfo-1-naphthyl)ethylenediamine (CL-AEDANS fragment) was prepared. This fragment has only one tryptophan residue at position 148. The compactness of the fragment whose intrachain disulfide bond was reduced in order for the tryptophan residue to fluoresce (reduced CL-AEDANS fragment) was studied in the early stages of refolding from 4 M guanidine hydrochloride by fluorescence energy transfer from Trp 148 to the AEDANS group. The AEDANS group attached to the SH group of a cysteine scarcely fluoresced when excited at 295 nm. For the reduced CL-AEDANS fragment, the fluorescence emission band of the Trp residue overlapped with the absorption band of the AEDANS group, and the fluorescence energy transfer was observed between Trp 148 and the AEDANS group in the absence of guanidine hydrochloride. In 4 M guanidine hydrochloride, the distance between the donor and the acceptor was larger, and the efficiency of the energy transfer became lower. The distance between Trp 148 and the AEDANS group for the intact protein estimated by using the energy-transfer data was in good agreement with that obtained by X-ray crystallographic analysis. By the use of fluorescence energy transfer, tryptophyl fluorescence, and circular dichroism at 218 nm, the kinetics of unfolding and refolding of the reduced fragment were studied. These three methods gave the same unfolding kinetic pattern. However, the refolding kinetics measured by fluorescence energy transfer were different from those measured by tryptophyl fluorescence and circular dichroism, the latter two giving the same kinetic pattern.(ABSTRACT TRUNCATED AT 250 WORDS)


Altered patterns of keratin expression in oral hairy leukoplakia: prognostic implications.
To establish why the lateral border of tongue is the site of predilection for the development of hairy leukoplakia (HL) and to understand its likely behavior, the pattern of keratin expression was compared in 8HL lesions with matched controls in an immunocytochemical study. Keratins 7, 8, 18 were absent in HL and normals; uniform basal keratin 19 was present in normals but much reduced in HL. Loss of conformationally sensitive epitopes of keratin 14 in lower epithelial layers was seen in HL. Overall expression of non-cornifying keratins 4/13 was reduced in HL and completely lost in the parakeratin zone. Expression of the high-turnover keratins 6/16 was reduced in HL. The HL keratin phenotype suggests that no dysplastic change is likely, but in contrast there is enhanced differentiation, which suggests a benign course for the condition.


Detecting and measuring areas of choriocapillaris low perfusion in intermediate, non-neovascular age-related macular degeneration.
Age-related macular degeneration (AMD) is a vision-threatening disease that affects the outer retina and choroid of elderly adults. Because photoreceptors are found in the outer retina and rely primarily on the trophic support of the underlying choriocapillaris, imaging of flow or lack thereof in choriocapillaris by optical coherence tomography angiography (OCTA) has great clinical potential in AMD assessment. We introduce a metric using OCTA, named "focal perfusion loss" (FPL) to describe the effects of age and non-neovascular AMD on choriocapillaris flow. Because OCTA imaging of choriocapillaris is vulnerable to artifacts-namely motion, projections, segmentation errors, and shadows-they are removed by postprocessing software. The shadow detection software is a machine learning algorithm recently developed for the evaluation of the retinal circulation and here adapted for choriocapillaris analysis. It aims to exclude areas with unreliable flow signal due to blocking of the OCT beam by objects anterior to the choriocapillaris (e.g., drusen, retinal vessels, vitreous floaters, and iris). We found that both the FPL and the capillary density were able to detect changes in the choriocapillaris of AMD and healthy age-matched subjects with respect to young controls. The dominant cause of shadowing in AMD is drusen, and the shadow exclusion algorithm helps determine which areas under drusen retain sufficient signal for perfusion evaluation and which areas must be excluded. Such analysis allowed us to determine unambiguously that choriocapillaris density under drusen is indeed reduced.


Custom-made segmental femoral replacement prosthesis in revision total hip arthroplasty.
Patients who present with failed total hip arthroplasty and significant proximal femoral bone loss pose a challenging reconstructive problem. When the integrity of the host proximal femur can be salvaged with cortical strut grafts, conventional long-stem femoral components can be used. If there is massive proximal femoral bone loss, hip salvage can be accomplished with a proximal femoral replacement prosthesis or an allograft-prosthesis composite. Although our early results with a proximal femoral replacement prosthesis were good, long-term results reveal a high rate of dislocation and acetabular component loosening, with an overall survivorship of 73% at 11 years. We have, therefore, limited the use of a proximal femoral replacement prosthesis to the elderly and inactive patient. We are encouraged by the preliminary results of total hip arthroplasty with a second-generation, modular, porous-coated, proximal femoral replacement prosthesis. Longer follow-up is required to determine whether these design modifications improve the results of this type of reconstructive procedure in revision total hip arthroplasty.


Effects of Different Land Use Types and Soil Depths on Soil Mineral Elements, Soil Enzyme Activity, and Fungal Community in Karst Area of Southwest China.
The current research was aimed to study the effects of different land use types (LUT) and soil depth (SD) on soil enzyme activity, metal content, and soil fungi in the karst area. Soil samples with depths of 0-20 cm and 20-40 cm were collected from different land types, including grassland, forest, Zanthoxylum planispinum land, Hylocereus spp. land and Zea mays land. The metal content and enzyme activity of the samples were determined, and the soil fungi were sequenced. The results showed that LUT had a significant effect on the contents of soil K, Mg, Fe, Cu and Cr; LUT and SD significantly affected the activities of invertase, urease, alkaline phosphatase and catalase. In addition, Shannon and Chao1 index of soil fungal community was affected by different land use types and soil depths. Ascomycota, Basidiomycota and Mortierellomycota were the dominant phyla at 0-20 cm and 20-40 cm soil depths in five different land types. Land use led to significant changes in soil fungal structure, while soil depth had no significant effect on soil fungal structure, probably because the small-scale environmental changes in karst areas were not the dominant factor in changing the structure of fungal communities. Additionally, metal element content and enzyme activity were related to different soil fungal communities. In conclusion, soil mineral elements content, enzyme activity, and soil fungal community in the karst area were strongly affected by land use types and soil depths. This study provides a theoretical basis for rational land use and ecological restoration in karst areas.


M918V RET mutation causes familial medullary thyroid carcinoma: study of 8 affected kindreds.
Germline mutations in codon 918 of exon 16 of the RET gene (M918T) are classically associated with multiple endocrine neoplasia type 2B (MEN 2B) with highly aggressive medullary thyroid cancer (MTC), pheochromocytoma and a unique phenotype. The objectives of this study are to describe the rare M918V RET mutation discovered in 8 MTC kindreds from Brazil lacking the MEN 2B phenotype classically observed in M918T patients and to investigate the presence of a founder effect for this germline mutation. Eight apparently sporadic MTC cases were diagnosed with the germline M918V RET mutation. Subsequently, their relatives underwent clinical and genetic assessment (n = 113), and M918V was found in 42 of them. Until today, 20/50 M918V carriers underwent thyroidectomy and all presented MTC/C-cell hyperplasia; the remainder carriers are on clinical follow-up. None of the M918V carriers presented clinical features of MEN 2B. Their clinical presentation was heterogeneous, and the age at tumor diagnosis ranged from 24 to 59 years. Lymph node metastases were present in 12/20 patients, and presumable distant metastases in 2/20; in contrast, we observed a carrier of up to 87 years of age without evidence of MTC. Ethnographic fieldwork and haplotype analyses suggested that the founder mutation first settled in that area fifteen generations ago and originated from Portugal. Our study is the first to demonstrate the RET M918V mutation co-segregating in 8 familial MTC kindreds with validated evidence of a founder effect. We suggest that M918V MTC should be clinically considered an American Thyroid Association (ATA) moderate-risk category.


Prognostic Value of Serum Caspase-Cleaved Cytokeratin-18 Levels before Liver Transplantation for One-Year Survival of Patients with Hepatocellular Carcinoma.
Cytokeratin (CK)-18 is the major intermediate filament protein in the liver and during hepatocyte apoptosis is cleaved by the action of caspases; the resulting fragments are released into the blood as caspase-cleaved cytokeratin (CCCK)-18. Higher circulating levels of CCCK-18 have been found in patients with hepatocellular carcinoma (HCC) than in healthy controls and than in cirrhotic patients. However, it is unknown whether serum CCCK-18 levels before liver transplantation (LT) in patients with HCC could be used as a prognostic biomarker of one-year survival, and this was the objective of our study with 135 patients. At one year after LT, non-survivors showed higher serum CCCK-18 levels than survivors (p = 0.001). On binary logistic regression analysis, serum CCCK-18 levels >384 U/L were associated with death at one year (odds ratio = 19.801; 95% confidence interval = 5.301-73.972; p < 0.001) after controlling for deceased donor age. The area under the receiver operating characteristic (ROC) curve of serum CCCK-18 levels to predict death at one year was 77% (95% CI = 69%-84%; p < 0.001). The new finding of our study was that serum levels of CCCK-18 before LT in patients with HCC could be used as prognostic biomarker of survival.


IL-1 secreting cell assay and its application to cells from patients with rheumatoid arthritis.
The cells within a population that were secreting interleukin-1 (IL-1) were enumerated and visualized by an ELISA-SPOT assay. Initial experiments designed to validate the assay revealed that the number of IL-1 beta spot forming cells was increased by exposing normal blood monocytes to LPS and that spot formation was prevented by incubating the cells with cycloheximide. Normal blood polymorphonuclear leucocytes (PMNs) produced IL-1 alpha and IL-1 beta in response to recombinant granulocyte monocyte colony stimulating factor (rhGMCSF) but not to cytochalasin B, calcium ionophore or LPS. Monocytes and PMN were isolated from the synovial fluid (SF) and blood of patients with rheumatoid arthritis (RA) and the ability of these cells to secrete IL-1 alpha and IL-1 beta compared. A higher proportion of SF derived monocytes were found to secrete IL-1 beta spontaneously compared to the corresponding blood cells. IL-1 alpha secreting monocytes were not detected although high numbers of IL-1 alpha secreting cells were found among cells isolated from rheumatoid synovium. By contrast SF PMNs did not produce IL-1 alpha or IL-1 beta whereas blood PMNs from some (3/8) RA patients produced IL-1 alpha and/or IL-1 beta. It is considered that the IL-1 ELISA-SPOT is a highly sensitive technique for detecting IL-1 secreting cells.


Amyloid-β and the failure to form mitochondrial cristae: a biomimetic study involving artificial membranes.
Alzheimer's disease (AD) is a degenerative disease of the central nervous system which causes irreversible damage to neuron structure and function. The main hypothesis concerning the cause of AD is excessive accumulation of amyloid-β peptides (Aβ). There has recently been a surge in studies on neuronal morphological and functional pathologies related to Aβ-induced mitochondrial dysfunctions and morphological alternations. What is the relation between the accumulation of Aβ in mitochondria, decreased production of ATP, and the large number of mitochondria with broken or scarce cristae observed in AD patients' neurons? The problem is complex, as it is now widely recognized that mitochondria function determines mitochondrial inner membrane (IM) morphology and, conversely, that IM morphology can influence mitochondrial functions. In our previous work, we designed an artificial mitochondrial IM, a minimal model system (giant unilamellar vesicle) mimicking the IM. We showed experimentally that modulation of the local pH gradient at the membrane level of cardiolipin-containing vesicles induces dynamic membrane invaginations similar to the mitochondrial cristae. In the present work we show, using our artificial IM, that Aβ renders the membrane unable to support the formation of cristae-like structures when local pH gradient occurs, leading to the failure of this cristae-like morphology. Fluorescent probe studies suggest that the dramatic change of membrane mechanical properties is due to Aβ-induced lipid bilayer dehydration, increased ordering of lipids, loss of membrane fluidity, and possibly to Aβ-induced changes in dynamic friction between the two leaflets of the lipid membrane.


The predictive of tumour markers CA 15-3, TPS and CEA in breast cancer recurrence.
The predictive values of tumour markers Carcinoma-Associated Antigen CA 15-3, Tissue Polypeptide Specific Antigen (TPS) and Carcinoembryonic Antigen (CEA) in recurrence of breast cancer are unclear. The aim of this study was to examine the predictive value of these markers in our population of 1448 patients with diagnosed breast cancer. Data and mean follow-up of 4.4 years were available on 1082 women of whom 277 had documented recurrence (mean follow up 5.7 years). The recurrence free patients had a mean follow up of 3.9 years. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CA 15-3, TPS and CEA for visceral, bony and locoregional recurrence were calculated. CA 15-3 was the most sensitive marker, 68% for visceral and 69% for bony recurrence. This compared with TPS, 64% and 51% and CEA, 27% and 46% for visceral and bony recurrence respectively. The positive predictive value of CA 15-3 at 47% for visceral and 54% for bony recurrence was greater than that for TPS (visceral 25%, bony 21%) or CEA (visceral 18%, bony 26%). The sensitivity of CA 15-3 and TPS for locoregional recurrence was low at 23% and 17% respectively. A combination of CA 15-3, TPS and CEA failed to increase the sensitivity of CA 15-3 for visceral recurrence. However, a marginally increased sensitivity was recorded for combined CA 15-3 and TPS (70%) and for combined CA 15-3, TPS and CEA (71%) in bony recurrence. The mean lead time effect in visceral recurrence for TPS and CA 15-3 were 8 and 10 months respectively. In patients with bony recurrence the mean lead time effect for TPS and CA 15-3 were 7.5 and 8.25 months. Mean lead time effect was increased to 9 and 11 months for bony and visceral recurrence respectively when CA 15-3 and TPS were combined. CA 15-3 remains the most sensitive tumour marker in breast cancer follow up with a significantly greater positive predictive value when compared to TPS or CEA. Both TPS and CEA failed to complement the sensitivity of CA 15-3 when measured in combination.


Analysis of airway epithelial regeneration and repair following endobronchial brush biopsy in sheep.
Understanding the fundamental processes involved in repairing the airway wall following injury is fundamental to understanding the way in which these processes are perturbed during disease pathology. Indeed complex diseases such as asthma and chronic obstructive pulmonary disease (COPD) have at their core evidence of airway wall remodeling processes that play a crucial functional role in these diseases. The authors sought to understand the dynamic cellular events that occur during bronchial airway epithelial repair in sheep. The injury was induced by endobronchial brush biopsy (BBr), a process that causes epithelial débridement and induces a consequential repair process. In addition, the current experimental protocol allowed for the time-dependent changes in airway wall morphology to be studied both within and between animals. The initial débridement was followed by evidence of dedifferentiation in the intact epithelium at the wound margins, followed by proliferation of cells both within the epithelium and in the deeper wall structures, notably in association with the submucosal glands and smooth muscle bundles. Seven days after injury, although the airway wall was thickened at the site of damage, the epithelial layer was intact, with evidence of redifferentiation. These studies, in demonstrating broad agreement with previous studies in small animals, indicate the wider relevance of this system as a comparative model and should provide a solid basis upon which to further characterize the critical cellular and molecular interactions that underlie both effective restitution and pathological repair.


Cellular Stress Responses in Radiotherapy.
Radiotherapy is one of the major cancer treatment strategies. Exposure to penetrating radiation causes cellular stress, directly or indirectly, due to the generation of reactive oxygen species, DNA damage, and subcellular organelle damage and autophagy. These radiation-induced damage responses cooperatively contribute to cancer cell death, but paradoxically, radiotherapy also causes the activation of damage-repair and survival signaling to alleviate radiation-induced cytotoxic effects in a small percentage of cancer cells, and these activations are responsible for tumor radio-resistance. The present study describes the molecular mechanisms responsible for radiation-induced cellular stress response and radioresistance, and the therapeutic approaches used to overcome radioresistance.


Review: Non-Invasive Brain Stimulation in Behavioral Addictions: Insights from Direct Comparisons With Substance Use Disorders.
Treatment models developed for substance use disorders (SUDs) are often applied to behavioral addictions (BAs), even though the correspondence between these forms of addiction is unclear. This is also the case for noninvasive brain stimulation (NIBS) techniques being investigated as potential treatment interventions for SUDs and BAs. to contribute to the development of more effective NIBS protocols for BAs. Two literature searches using PubMed and Google Scholar were conducted identifying a total of 35 studies. The first search identified 25 studies examining the cognitive and neurophysiological overlap between BAs and SUDs. The second search yielded 10 studies examining the effects of NIBS in BAs. Impulsivity and cravings show behavioral and neurophysiologic overlaps between BAs and SUDs, however, other outcomes like working-memory abilities or striatal connectivity, differ between BAs and SUDs. The most-employed NIBS target in BAs was dorsolateral prefrontal cortex (DLPFC), which was associated with a decrease in cravings, and less frequently with a reduction of addiction severity. Direct comparisons between BAs and SUDs revealed discrepancies between behavioral and neurophysiological outcomes, but overall, common and distinctive characteristics underlying each disorder. The lack of complete overlap between BAs and SUDs suggests that investigating the cognitive and neurophysiological features of BAs to create individual NIBS protocols that target risk-factors associated specifically with BAs, might be more effective than transferring protocols from SUDs to BAs. Individualizing NIBS protocols to target specific risk-factors associated with each BA might help to improve treatment interventions for BAs. (Am J Addict 2019;00:1-23).


Contraception: prospect of new contraceptives.
At a metting of eminent international scientists in Cambridge, England, last September, several promising experiments were described that tested the feasibility of contraception based on pituitary-regulating hormones produced by the hypothalamus, an area at the base of the brain, that regulates the pituitary gland. There is still much basic research needed but preliminary results are promising. 2 Johns Hopkins University researchers are developing a method for male sterilization by the use of chemicals instead of surgery. The method has been successful with test animals, and has had no adverse effects on their sex lives. Clinical trials will begin this summer, if approved by the hospital research committee.


Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity.
Polyamidoamine (PAMAM) and polypropylenimine (PPI) dendrimers are the commercially available and most widely used dendrimers in pharmaceutical sciences and biomedical engineering. In the present study, the loading and release behaviors of generation 3 PAMAM and generation 4 PPI dendrimers with the same amount of surface amine groups (32 per dendrimer) were compared using phenylbutazone as a model drug. The dendrimer-phenylbutazone complexes were characterized by (1)H nuclear magnetic resonance and nuclear Overhauser effect techniques, and the cytotoxicity of each dendrimer was evaluated. Aqueous solubility results suggest that the generation 3 PAMAM dendrimer has a much higher loading ability towards phenylbutazone in comparison with the generation 4 PPI dendrimer at high phenylbutazone-dendrimer feeding ratios. Drug release was much slower from the generation 3 PAMAM matrix than from the generation 4 PPI dendrimer. In addition, the generation 3 PAMAM dendrimer is at least 50-fold less toxic than generation 4 PPI dendrimer on MCF-7 and A549 cell lines. Although the nuclear Overhauser effect nuclear magnetic resonance results reveal that the generation 4 PPI dendrimer with a more hydrophobic interior encapsulates more phenylbutazone, the PPI dendrimer-phenylbutazone inclusion is not stable in aqueous solution, which poses a great challenge during drug development.


Keep an open mind.
On placement with a home treatment team, I went with a social worker and an interpreter to see a client with depression. The client's first language was Arabic and her English was limited, so using an interpreter enabled us to communicate with her more effectively.


Anaphylactoid reactions to glycopeptide antibiotics.
Anaphylactoid reactions to vancomycin have been reported consistently since the earliest clinical trials. Signs and symptoms of the reaction, which usually occur during the first dose, can range in severity from mild pruritus and upper body flushing, to dramatic hypotension and cardiovascular arrest. The frequency of the reaction, and its severity, is proportional to the total dose administered and the infusion rate. Recent prospective investigations report that when 1 g of vancomycin is administered over 60 min to normal volunteers and infected patients, between 50-90% of adults will have a reaction, although most are mild and of little clinical consequence. Vancomycin causes a release of histamine into blood, and the severity of the reaction is proportional to the amount of histamine released. Tachyphylaxis rapidly develops in most persons, although decreasing the dose, or increasing the infusion time will also help alleviate the signs and symptoms. Antihistamine H1 blocking agents are also effective in preventing the reaction. Teicoplanin, a new glycopeptide antibiotic, does not appear to cause histamine release or related symptoms, even when administered at a more rapid rate than vancomycin.


Whiplash injury and peer copying.
Whiplash injury has increased during the past 40 years. Peer copying has occurred both among patients and practitioners. The importance of understanding the common course of the injury is stressed and simpler and less costly management suggested. Also noted is the importance of digesting whole articles. Reliance upon abstracted material alone or parts of articles may prove to be misleading and may lead to perpetuating questionable information.


Effect of caffeine and high potassium on normal and dystrophic mouse EDL muscles at various developmental stages.
EDL muscles from normal and dystrophic (dy2j) mice of various ages were examined. Muscles were divided into three groups according to age: 7 to 14 days postnatal, 16 to 21 days postnatal, and 6 months old, to assess age and/or phenotype related differences in the muscle response to caffeine or high K+. The response of normal muscles to caffeine decreased with age and reached adult characteristics between the second and third week of postnatal life. Their response to high K+ also changed during postnatal development; specifically, the time taken to recover to 50% pretest twitch tension decreased with age, probably reflecting developmental changes in Cl- conductance. Up to 21 days of age, the sensitivity of dystrophic muscles to both caffeine and high K+ was essentially similar to normal, while marked differences were observed in the adult. Taken altogether, our results suggest that while the maturation of a number of systems might be delayed in dystrophic muscles at preclinical stages of the disease, their e-c coupling and SR function (Ca2+ release and reuptake) appear to be quite normal. Our results further suggest that the "abnormal" responses of dystrophic muscles at more advanced stages of the disease, when challenged by drugs acting on either of these systems, may be explained in terms of changes in muscle fiber type proportions.


Repression of the stress granule protein G3BP2 inhibits immune checkpoint molecule PD-L1.
Mounting evidence suggests that cancer stemness and immunosuppression are related, but the underlying mechanisms behind these are not clear. We previously reported that the stress granule-associated protein G3BP2 is involved in the regulation of tumor-initiating (stem) cells. In this study, we show that this protein also upregulates the immune checkpoint molecule PD-L1 under conditions of stress in breast and glioblastoma cancer cells, revealing a previously unknown connection between stemness programs, stress responses, and immune checkpoint control. We also identified a significant correlation between G3BP2 and PD-L1 co-expression in tumor tissues from cancer patients. To assess the targetability of G3BP2, we employed a small molecule (C108) that binds G3BP2 and interferes with the stress response. Tumors treated with C108 had increased CD8 T-cell proliferation and infiltration. Moreover, treatment of breast tumor-bearing mice with C108 resulted in a significant survival benefit and long-term cures. Cancer cells treated with C108 or cancer cells with genetically repressed G3BP2 had decreased PD-L1 expression due to enhanced mRNA degradation. Our study provides a compelling mechanism linking stress granule formation and immune checkpoint program of cancer, suggesting this link may provide new opportunities for improving anticancer immunotherapy.


Muscle blood flow responses to dynamic exercise in young obese humans.
Exercise is a common nonpharmacological way to combat obesity; however, no studies have systematically tested whether obese humans exhibit reduced skeletal muscle blood flow during dynamic exercise. We hypothesized that exercise-induced blood flow to skeletal muscle would be lower in young healthy obese subjects (body mass index of >30 kg/m(2)) compared with lean subjects (body mass index of <25 kg/m(2)). We measured blood flow (Doppler Ultrasound of the brachial and femoral arteries), blood pressure (auscultation, Finapress), and heart rate (ECG) during rest and two forms of single-limb, steady-state dynamic exercise: forearm exercise (20 contractions/min at 4, 8, and 12 kg) and leg exercise (40 kicks/min at 7 and 14 W). Forearm exercise increased forearm blood flow (FBF) similarly in both groups (P > 0.05; obese subjects n = 9, lean subjects n = 9). When FBF was normalized for perfusion pressure, forearm vascular conductance was not different between groups at increasing workloads (P > 0.05). Leg exercise increased leg blood flow (LBF) similarly in both groups (P > 0.05; obese subjects n = 10, lean subjects n = 12). When LBF was normalized for perfusion pressure, leg vascular conductance was not different between groups at increasing workloads (P > 0.05). These results were confirmed when relative blood flow was expressed at average relative workloads. In conclusion, our results show that obese subjects exhibited preserved FBF and LBF during dynamic exercise.


[The development of mixed emotional and behavioral disorders in children raised in foster care institutions].
The aim of the work was to evaluate the changes brought by time in the psychoemotional state of neglected and abandoned children (exhibiting disturbed social relations), which were displayed in childrens' behavior. The longitudinal research has been carried out by the epidemiological case-control scheme. Two groups of children were examined. During the first test the study group was formed by 70 (44 boys and 26 girls) neglected and abandoned children drew up from foster care institutions. The control group was adequate in age and sex to the study group. It included 70 (44 boys and 26 girls) children from traditional families. The second test was carried out two was years later. It was applied to the same groups of children, only this time 50 (32 boys and 18 girls) children from the study and from the control group were tested. Mixed psychoemotional and behavioral disorders were evaluated by experts (teachers from foster care institutions, nurseries and schools) who applied the scale of indicators. The results gave evidence of psychoemotional problems in the neglected and abandoned children growing up in foster care institutions: they were nervous, exhibited aggression, difficulties in their education emerge. The behavior and emotions shape themselves in frustration and depression. These disorders tend to grow and become more serious in the course of time, social behavior deviations and social health development disorders emerged. The psychoemotional health development of neglected and abandoned children evoked difficulties in their psychological adaptation.


Molecularly imprinted solid-phase extraction for the selective determination of methamphetamine, amphetamine, and methylenedioxyphenylalkylamine designer drugs in human whole blood by gas chromatography-mass spectrometry.
A novel method is described for the extraction of methamphetamine, amphetamine, and methylenedioxyphenylalkylamine designer drugs, such as 3,4-methylenedioxy-methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine, and 3,4-(methylenedioxyphenyl)-2-butanamine, from human whole blood using molecularly imprinted solid-phase extraction as highly selective sample clean-up technique. Whole blood samples were diluted with 10 mmol/L ammonium acetate (pH 8.6) and applied to a SupelMIP-Amphetamine molecularly imprinted solid-phase extraction cartridge. The cartridge was then washed to eliminate interferences, and the amphetamines of interest were eluted with formic acid/methanol (1:100, v/v). After derivatization with trifluoroacetic anhydride, the analytes were quantified using gas chromatography-mass spectrometry. Recoveries of the seven amphetamines spiked into whole blood were 89.1-102%. The limits of quantification for each compound in 200 μL of whole blood were between 0.25 and 1.0 ng. The maximum intra- and inter-day coefficients of variation were 9.96 and 13.8%, respectively. The results show that methamphetamine, amphetamine, and methylenedioxyphenylalkyl-amine designer drugs can be efficiently extracted from crude biological samples such as whole blood by molecularly imprinted solid-phase extraction with good reproducibility. This extraction method will be useful for the pretreatment of human samples before gas chromatography-mass spectrometry.


Relative accuracy of grid references derived from postcode and address in UK epidemiological studies of overhead power lines.
In the UK, the location of an address, necessary for calculating the distance to overhead power lines in epidemiological studies, is available from different sources. We assess the accuracy of each. The grid reference specific to each address, provided by the Ordnance Survey product Address-Point, is generally accurate to a few metres, which will usually be sufficient for calculating magnetic fields from the power lines. The grid reference derived from the postcode rather than the individual address is generally accurate to tens of metres, and may be acceptable for assessing effects that vary in the general proximity of the power line, but is probably not acceptable for assessing magnetic-field effects.


Detection of Orientia tsutsugamushi in Novel Trombiculid Mite Species in Northern Tamil Nadu, India: Use of Targeting the Multicopy traD Gene.
Detection of Orientia tsutsugamushi DNA in a trombiculid mite chigger species suggests that it might be a potential vector of scrub typhus in an endemic area. Over a period of 20 mo, 85 rats were trapped, 57 had chiggers that were identified by standard morphometric techniques. The chigger pools were assessed by performing PCR assays targeting fragments of the single-copy genes 56 kDa type-specific antigen gene (TSA56) by nested PCR and the 47 kDa (htrA) quantitative real-time PCR (qPCR). The novel traD SYBR green assay that detects a multicopy gene was also performed. In total, 27 chigger pools were positive by traD qPCR, of which only 7 were positive by 47 kDa qPCR and in 3 of these, 56 kDa gene was amplified by nested PCR. Orientia tsutsugamushi-specific DNA was detected in Ascoschoengastia spp., Schoengastiella ligula, Leptotrombidium rajasthanense, Leptotrombidium deliense, and Leptotrombidium jayawickremei chigger pools. Therefore, they could be potential vectors of scrub typhus in Southern India. The three 56 kDa sequences belonged to TA716 genotype and Kato genogroup. Further studies are needed to confirm these chigger species as scrub typhus vectors in Northern Tamil Nadu.


Stability of white wine proteins: combined effect of pH, ionic strength, and temperature on their aggregation.
Protein haze development in white wines is an unacceptable visual defect attributed to slow protein unfolding and aggregation. It is favored by wine exposure to excessive temperatures but can also develop in properly stored wines. In this study, the combined impact of pH (2.5-4.0), ionic strength (0.02-0.15 M), and temperature (25, 40, and 70 °C) on wine protein stability was investigated. The results showed three classes of proteins with low conformational stability involved in aggregation at room temperature: β-glucanases, chitinases, and some thaumatin-like protein isoforms (22-24 kDa). Unexpectedly, at 25 °C, maximum instability was observed at the lower pH, far from the protein isoelectric point. Increasing temperatures led to a shift of the maximum haze at higher pH. These different behaviors could be explained by the opposite impact of pH on intramolecular (conformational stability) and intermolecular (colloidal stability) electrostatic interactions. The present results highlight that wine pH and ionic strength play a determinant part in aggregation mechanisms, aggregate characteristics, and final haze.


Japanese herbal medicine, inchinkoto, inhibits inducible nitric oxide synthase induction in interleukin-1β-stimulated hepatocytes.
A herbal medicine, kampo inchinkoto (TJ-135), is used to treat jaundice and liver fibrosis in patients with cirrhosis. In the inflamed liver, proinflammatory cytokines stimulate the induction of inducible nitric oxide synthase (iNOS) gene expression. Over-production of nitric oxide (NO) by iNOS has been implicated as a factor in liver injury. We examined interleukin (IL)-1β-stimulated hepatocytes as a simple in vitro injury model to determine liver-protective effects of TJ-135. The objective was to investigate whether TJ-135 influences iNOS induction and to determine its mechanism. Primary cultured rat hepatocytes were treated with IL-1β in the presence or absence of TJ-135. The induction of iNOS and its signaling pathway were analyzed. IL-1β produced increased levels of NO. This effect was inhibited by TJ-135, which exerted its maximal effects at 3 mg/mL. TJ-135 decreased the levels of iNOS protein and its mRNA expression. Experiments with nuclear extracts revealed that TJ-135 inhibited the translocation of nuclear factor-κB (NF-κB) to the nucleus and its DNA binding. TJ-135 also inhibited the activation of Akt, resulting in the reduction of type I IL-1 receptor mRNA and protein expression. Transfection experiments with iNOS promoter-luciferase constructs demonstrated that TJ-135 suppressed iNOS induction by inhibition of promoter transactivation and mRNA stabilization. TJ-135 reduced the expression of an iNOS gene antisense-transcript. Delayed administration or withdrawal of TJ-135 after IL-1β addition also inhibited iNOS induction. RESULTS indicate that TJ-135 inhibits the induction of iNOS at both transcriptional and post-transcriptional steps, leading to the prevention of NO production. TJ-135 may have therapeutic potential for various liver injuries through the suppression of iNOS induction.


Differences among patients with and without nonalcoholic fatty liver disease having elevated alanine aminotransferase levels at various stages of metabolic syndrome.
The prevalence of nonalcoholic fatty liver disease (NAFLD) in the non-obese population has increased and NAFLD is not always recognized in individuals with metabolic syndrome (MS). The risk of cirrhosis is higher in patients having NAFLD with elevated alanine aminotransferase (ALT) levels than in those having NAFLD with normal ALT levels. To measure the differences in clinical factors associated with NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and to measure differences in metabolites between MS subjects with and without NAFLD having elevation of ALT. Among 7,054 persons undergoing health check-ups, we included 3,025 subjects who met the selection criteria. We measured differences in clinical factors for NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and compared metabolites between subjects with and without NAFLD having elevation of ALT in 32 subjects with MS. The prevalence of NAFLD and NAFLD having elevation of ALT was significantly progressively greater in subjects with Non-MS, Pre-MS, and MS (p <0.001, respectively). In the Non-MS group, there were significant differences between subjects with and without NAFLD having elevation of ALT with respect to body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, hemoglobin A1c, uric acid, aspartate aminotransferase (AST); In the Pre-MS group, there were significant differences in BMI, hypertension, AST, and gamma-glutamyl transpeptidase (GGT); In the MS group, there were significant differences in HDL-C, impaired glucose tolerance, AST, and GGT. There were significant differences in levels of metabolites of nicotinamide, inosine, and acetyl-L-carnitine between MS subjects with and without NAFLD having elevation of ALT (all p <0.05). Although NAFLD having elevation of ALT is important for development of NAFLD, differences in factors associated with NAFLD having elevation of ALT at various stages of MS should be considered. Additionally, several metabolites may play roles in the identification of risk for NAFLD in individuals with MS.


Successful mast-cell-targeted treatment of chronic dyspareunia, vaginitis, and dysfunctional uterine bleeding.
Dyspareunia, vaginitis and dysfunctional uterine bleeding (DUB) are common problems which, despite their polygenicity, commonly appear idiopathic and treatment-refractory. Mast cell (MC) activation syndrome (MCAS) is a newly-recognised, prevalent, chronic multisystem polymorbidity of general themes of inflammation ± allergic-type phenomena ± aberrant growth/development in assorted tissues. MCs produce significant quantities of heparin, too. As such, MCAS may underlie some cases of chronic dyspareunia, vaginitis or DUB. We report five such patients; all who responded well to MC-targeted treatment. We review aspects of MC biology and pathobiology of potential relevance to otherwise idiopathic persistent inflammatory or coagulopathic genital tract problems. Diagnostic testing for MCAS may be warranted in some patients with chronic dyspareunia, vaginitis or DUB (especially patients whose histories well fit the general profile of MCAS), and prospective therapeutic trials of MC-directed topical and/or systemic therapies may be warranted in such populations. Impact statement What is already known on this subject? Chronic, idiopathic, treatment-refractory female genital tract inflammation or bleeding are common problems for which mast cell (MC) disease, previously generally thought to consist of just rare cases of mastocytosis, and is seldom considered in the differential diagnosis. What do the results of this study add? The substantial prevalence of the newly recognised 'mast cell activation syndrome' (MCAS), featuring chronic inappropriate MC activation with little-to-no MC neoplasia, and its clinical presentation with chronic multisystem inflammation ± allergic-type phenomena ± aberrant growth/development in assorted tissues, raises the possibility that MCAS might underlie the aforementioned genital tract problems, especially in patients whose larger clinical presentations fit the MCAS profile. We report five example patients (among many more we have similarly treated) who enjoyed excellent responses to safe, inexpensive MC-targeted treatments, often given just intravaginally. What are the implications of these findings for clinical practice and/or further research? Our report identifies a potentially significant new MC-focused direction, of relevance to millions of affected women worldwide, for clinical treatment as well as for basic and clinical research, which historically has yielded major advancements disappointingly disproportionate to the scope of the affected population.


Partial seizures triggering infantile spasms in the presence of a basal ganglia glioma.
Infantile spasms associated with brain tumors have been reported. A focal cortical lesion can induce infantile spasms by triggering the brainstem and basal ganglia in this vulnerable age group. We report the case of a female infant with a low-grade glioma in the right basal ganglia, spreading to the cortical area. She presented at the age of five months with left hemiparesis and partial seizures. She developed infantile spasms at the age of 12 months. This is the first video clip report of partial seizures triggering symmetrical spasms in series, secondary to a basal ganglia glioma extending to the cortex. [Published with video sequences].


Cardiac dysrhythmias during donor care.
Organ procurement coordinators must treat various cardiac dysrhythmias (arrhythmias), including rhythm disturbances that may cause or follow a cardiac arrest, in about 15% to 50% of donors. Treatment decisions should be based on the particular dysrhythmia and its effect on donor blood pressure. Medications selected should be effective but short acting. In this article, data available in publications located through a PubMed search are reviewed and specific dysrhythmias that are likely to occur during donor care are described. Treatment recommendations are based on guidelines from the American Heart Association.


Eotaxin/CCL11 is involved in acute, but not chronic, allergic airway responses to Aspergillus fumigatus.
Eotaxin/CCL11 is a major chemoattractant for eosinophils and Th2 cells. As such, it represents an attractive target in the treatment of allergic disease. The present study addresses the role of eotaxin/CCL11 during acute and chronic allergic airway responses to the fungus Aspergillus fumigatus. Mice lacking the eotaxin gene (Eo-/-) and wild-type mice (Eo+/+) were sensitized to A. fumigatus and received either an intratracheal challenge with soluble A. fumigatus antigens (acute model) or an intratracheal challenge with live A. fumigatus spores or conidia (chronic model). Airway hyperresponsiveness and eosinophil, but not T cell, recruitment were significantly decreased at 24 h after the soluble allergen in A. fumigatus-sensitized Eo-/- mice compared with similarly sensitized Eo+/+ mice. In contrast, the development of chronic allergic airway disease due to A. fumigatus conidia was not altered by the lack of eotaxin. Together, these data suggest that eotaxin initiates allergic airway disease due to A. fumigatus, but this chemokine did not appear to contribute to the maintenance of A. fumigatus-induced allergic airway disease.


Explainable artificial intelligence in forensics: Realistic explanations for number of contributor predictions of DNA profiles.
Machine learning obtains good accuracy in determining the number of contributors (NOC) in short tandem repeat (STR) mixture DNA profiles. However, the models used so far are not understandable to users as they only output a prediction without any reasoning for that conclusion. Therefore, we leverage techniques from the field of explainable artificial intelligence (XAI) to help users understand why specific predictions are made. Where previous attempts at explainability for NOC estimation have relied upon using simpler, more understandable models that achieve lower accuracy, we use techniques that can be applied to any machine learning model. Our explanations incorporate SHAP values and counterfactual examples for each prediction into a single visualization. Existing methods for generating counterfactuals focus on uncorrelated features. This makes them inappropriate for the highly correlated features derived from STR data for NOC estimation, as these techniques simulate combinations of features that could not have resulted from an STR profile. For this reason, we have constructed a new counterfactual method, Realistic Counterfactuals (ReCo), which generates realistic counterfactual explanations for correlated data. We show that ReCo outperforms state-of-the-art methods on traditional metrics, as well as on a novel realism score. A user evaluation of the visualization shows positive opinions of end-users, which is ultimately the most appropriate metric in assessing explanations for real-world settings.


Compared with dietary monounsaturated and saturated fat, polyunsaturated fat protects African green monkeys from coronary artery atherosclerosis.
Atherogenic diets enriched in saturated, n-6 polyunsaturated, and monounsaturated fatty acids were fed to African green monkeys for 5 years to define effects on plasma lipoproteins and coronary artery atherosclerosis. The monkeys fed polyunsaturated and monounsaturated fat had similar plasma concentrations of LDL cholesterol, and these values were significantly lower than for LDL in the animals fed saturated fat. Plasma HDL cholesterol concentrations were comparable in animals fed saturated and monounsaturated fat and were significantly higher than in animals fed polyunsaturated fat. Thus, the monounsaturated fat group had the lowest LDL/HDL ratio. LDL particle size was largest in the saturated and monounsaturated fat groups, significantly larger than in the polyunsaturated fat group. LDL particle enrichment with cholesteryl oleate was the greatest in the animals fed monounsaturated fat, next greatest in the saturated fat-fed animals, and was least in the polyunsaturated fat-fed animals. Coronary artery atherosclerosis as measured by intimal area was less in the polyunsaturated fat compared with the saturated fat groups, was less in the animals fed polyunsaturated fat compared with the monounsaturated fat-fed animals, but did not differ between the monounsaturated and saturated fat groups. Cholesteryl ester, particularly cholesteryl oleate, accumulation in the coronary arteries was also similar between groups fed monounsaturated and saturated fat but was minimal in the animals fed polyunsaturated fat. In sum, the monkeys fed monounsaturated fat developed equivalent amounts of coronary artery atherosclerosis as those fed saturated fat, but monkeys fed polyunsaturated fat developed less. The beneficial effects of the lower LDL and higher HDL in the animals fed monounsaturated fat apparently were offset by the atherogenic shifts in LDL particle composition. Dietary polyunsaturated fat appears to result in the least amount of coronary artery atherosclerosis because it prevents cholesteryl oleate accumulation in LDL and the coronary arteries in these primates.


Inner child of the past: long-term protective role of childhood relationships with mothers and fathers and maternal support for mental health in middle and late adulthood.
National longitudinal studies that investigate the long-term association between early family life and mental health in middle and older adulthood are limited. This study aims to fill the gap by examining the protective effect of positive childhood relationships with mothers and fathers and parental support against depression among women and men in middle and late adulthood. The sample of 12,606 adults (7319 females; 5287 males) from the US Health and Retirement Study was nationally representative with the inclusion of 7 depression measures from 2008 to 2018. Two depression measures, CESD-8 scale and binary indicators of severe depressive symptoms, were used. Generalized estimation equations (GEE)-negative binomial models were estimated for CESD-8 and GEE-logit models were estimated for the binary indicator of severe depression. This study aimed to assess how positive parent-child relationships and maternal support protect the mental health of women and men in adulthood. Other risk and psychosocial factors, such as childhood depression, traumatic life events, stressful life events, marital status, and social support in adulthood were adjusted for. Positive childhood relationships with mothers, fathers, or both parents and increased maternal support were associated with a lower risk of depression among both females and males from middle to old age, even if they experienced trauma, stressful life events, divorce, singlehood, widowhood, or little social support. Females benefited more psychologically than males from positive mother-daughter relationships and high-quality relationships with both parents. However, compared to mother-child relationships, positive father-child relationships protected men better psychosocially than females. Findings underscore the importance of fathers' roles in promoting their children's, especially sons', emotional well-being. Interventions in early mother-child and father-child relationships and parental support are crucial for healthy aging in mental development.


Cadmium distribution and chemical fate in soybean plants.
The distribution and chemical behavior of Cd(2+) in tissues and its chemical form in xylem water of soybean plants (cv. Williams) were investigated. Following root absorption, Cd is strongly retained by roots, with only 2% of the accumulated Cd being transported to leaves; as much as 8% was transported to seeds during seed filling. In vivo xylem exudates contained two anionic Cd complexes in addition to inorganic forms of Cd. Once accumulated in root and leaf tissues, Cd rapidly equilibrated between the insoluble, soluble, and organelle fractions. Of the solubles, which contain 50% of the Cd, >50% was associated with components of >10,000 molecular weight, and <8% was associated with <500 molecular weight components. Cadmium accumulated in soybean seeds was primarily associated with cotyledons. Fractionation of seeds showed the soy proteinate and soy whey to contain 32 and 50% of the accumulated Cd, respectively.


Stem-like cells in human hepatoblastoma.
Hepatoblastoma is a pediatric liver tumor with epithelial components resembling embryonal and fetal liver cells. The existence of teratoid hepatoblastoma suggests the presence of stem cells in hepatoblastoma. The aim of this study was to analyze the expression of stem cell markers in hepatoblastomas. We studied specimens from 10 hepatoblastomas. Five of the hepatoblastomas were of epithelial and five of mixed type. Immunohistochemistry (IHC) for the stem cell markers CD34, Thy1, c-kit, and the hepatic or biliary lineage markers CK-18, OCH, CK-7, and CD56 was performed. Double IHC for stem cell and lineage markers was used to identify putative liver stem cells. The different markers showed distinct distributions on the tumor cells. Cells in atypical ducts were found to express simultaneously stem cell markers and hepatocytic or biliary lineage markers. Other cells in connective tissue showed c-kit expression, but not hepatic or biliary marker expression. The data show the presence of different cell populations bearing stem cell markers in human hepatoblastoma. Ductal cells co-expressing stem cell markers and hepatic lineage markers phenotypically resemble hepatic stem-like cells. These findings support the thesis that stem cells play a role in the histogenesis of hepatoblastoma.


Examination of transforming growth factor beta1 expression in the serum and tumor tissue of gastric cancer.
The objective of this study was to evaluate the relationship between transforming growth factor beta1 (TGF-beta1) expression in serum and tissue of gastric cancer and factors of clinical pathology, and to evaluate its clinical significance as a malignant potential parameter. Serological analysis of TGF-beta1 was studied in 110 patients who underwent gastric cancer surgery; there were 39 control subjects. TGF-beta1 immunohistochemical expression was studied in 50 specimens of 110 gastric cancers. The positive rate was compared with factors of clinical pathology. Serological analysis indicated that the preoperative serum TGF-beta1 level was significantly higher in the group that had invasion of subserosa and penetration of serosa than in the group that had invasion of mucosa, muscularis mucosa, submucosa, and muscularis propia (P = 0.04). Immunohistochemical analysis indicated that TGF-beta1 expression of gastric cancer that was a high-grade malignancy had a higher positive rate. The study shows that evaluation of TGF-beta1 level in preoperative serum and tumor tissue of gastric cancer can be useful for determining a parameter of grade of malignancy in gastric cancer.


Subtyping the irritable bowel syndrome by predominant bowel habit: Rome II versus Rome III.
The agreement between subtyping irritable bowel syndrome (IBS) patients based on Rome II criteria versus Rome III criteria is unknown. To compare IBS subtyping based on Rome II versus III criteria. The Rome II Modular Questionnaire and the Bristol Stool Form Scale (one-week diary cards) were completed by 249 IBS patients. Based on the Rome II criteria, patients were defined as having diarrhoea- or constipation-predominant IBS, or alternating IBS. Based on the Rome III criteria, patients were divided into IBS with constipation, IBS with diarrhoea, mixed IBS or unsubtyped IBS. Agreement between Rome II and Rome III was assessed with kappa statistics. Based on Rome II there were 92 diarrhoea-predominant IBS, 45 constipation-predominant IBS and 112 alternating IBS, and based on Rome III 97 IBS with diarrhoea, 77 IBS with constipation, 16 mixed IBS and 59 unsubtyped IBS. The agreement between Rome II and Rome III subgroups was 46% (kappa = 0.19). Changes from the constipation to the diarrhoea subgroups and vice versa were uncommon (8% of patients). The majority of changes occurred from/to the alternating IBS, mixed IBS and unsubtyped IBS subgroups. There is poor agreement between subtyping of IBS patients based on Rome II versus Rome III criteria.


[Radiomanometric studies of bile flow during surgery on extrahepatic biliary ducts: effects on postoperative course in 1600 patients after follow-up for more than 5 years (author's transl)].
The use of a simple, rapid, and reliable method for studying the anatomy and physiopathology of the main biliary pathway during operation by means of radiomanometry is described. This procedure enables a rational and precise therapeutic decision to be taken, as shown by comparing the results obtained in 1600 cases after a period of 5 years, with the interpretation of the initial radiomanometric findings and the type of operation performed. The overall rate of error based on the radiomanometric results, and leading to erroneous therapy, was 2 p. cent (0.43 p. cent excessive and 1.57 p. cent insufficient). No complications due to the method were observed. The main points noted were the absence of wounds to the main biliary pathway and of external bile tract fistulae, and a considerable reduction in the number of repeat operations and postcholecystectomy syndromes (1.5 p. cent).


Urban-rural and educational differentials in marital status in China.
Since 1950, laws aimed at delaying marriage have been 1 of the major means of slowing population growth in China, where marriage is nearly universal. Age at marriage has risen in recent decades, but not to the same extent in all localities. This article uses cross-tabulated data from China's 1982 census to assess the effects of urban-rural residence and educational level on the ages at which men and women have been marrying. The data also reveal the effects of residence and education on widowhood, divorce, and current marital status. As expected, exposure to development, indicated by urban residence and higher education, is associated with later marriage, but it also increases the likelihood of ever marrying, especially for men. Women's tendency to seek social mobility by marrying men from economically more developed areas results in bachelorhood for a substantial percentage of rural men, especially those who are illiterate.


Pressure-induced orientational glass phase in molecular para-hydrogen.
We propose a theoretical description of a possible orientational glass transition in solid molecular para-hydrogen and ortho-deuterium under pressure supposing that they are mixtures of J=0 and J=2 states of molecules. The theory uses the basic concepts and methods of standard spin-glass theory. We expect our orientational glass to correspond to the II' phase of the high-pressure hydrogen phase diagram.


Development of A Machine Learning Algorithm to Classify Drugs Of Unknown Fetal Effect.
Many drugs commonly prescribed during pregnancy lack a fetal safety recommendation - called FDA 'category C' drugs. This study aims to classify these drugs into harmful and safe categories using knowledge gained from chemoinformatics (i.e., pharmacological similarity with drugs of known fetal effect) and empirical data (i.e., derived from Electronic Health Records). Our fetal loss cohort contains 14,922 affected and 33,043 unaffected pregnancies and our congenital anomalies cohort contains 5,658 affected and 31,240 unaffected infants. We trained a random forest to classify drugs of unknown pregnancy class into harmful or safe categories, focusing on two distinct outcomes: fetal loss and congenital anomalies. Our models achieved an out-of-bag accuracy of 91% for fetal loss and 87% for congenital anomalies outperforming null models. Fifty-seven 'category C' medications were classified as harmful for fetal loss and eleven for congenital anomalies. This includes medications with documented harmful effects, including naproxen, ibuprofen and rubella live vaccine. We also identified several novel drugs, e.g., haloperidol, that increased the risk of fetal loss. Our approach provides important information on the harmfulness of 'category C' drugs. This is needed, as no FDA recommendation exists for these drugs' fetal safety.


Synthesis of Chiral beta 3-aminoxy peptides.
A series of chiral beta(3)-aminoxy acids or amides with various side chains have been synthesized via two different approaches. One is the Arndt-Eistert homologation approach, using chiral alpha-aminoxy acids as starting materials. The other approach, utilizing the enantioselective reduction of beta-keto esters catalyzed by baker's yeast or chiral Ru(II) complexes, produces chiral beta(3)-aminoxy acids with nonproteinaceous side chains. The oligomers of beta(3)-aminoxy acids can be readily prepared using EDCI/HOAt as the coupling reagent.


Effects of 35 C heat treatments on photosensitive grand rapids lettuce seed germination.
Grand Rapids lettuce (Lactuca sativa L.) seeds were given 35 C heat treatments to increase photodormancy in a subsequent 20 C dark period. Short heat treatments (1-5 hours) induced a significant germination percentage increase of from 16% to over 50% depending on seed lot. With longer heat treatments dark germination percentage was gradually reduced to zero. If given at the end of 35 C, far red or red followed by far red further increased the amount of dark germination.Thermodormancy also delayed red-stimulated germination by 10 hours or more when red was given following a long 35 C treatment. The presence of Pfr was required during this time since far red light remained effective in reversing at least 50% of the red stimulation for up to 16 hours compared to only 4 hours in nonheat-treated seeds.


Mortality risk in a sample of emergency department patients who use cocaine with alcohol and/or cannabis.
Illicit drug use is common among emergency department (ED) patients, yet the association between drug use and subsequent mortality is not well understood. This study examines 36-month mortality rates for a sample of ED patients based on reported use of alcohol, cannabis, and cocaine, both individually and in combination. Patients (N = 1669) from 2 urban EDs were surveyed at the time of the visit. The patient survey included the Alcohol Smoking and Substance Involvement Screening Test (ASSIST) and information on physical and mental health, health care utilization, and risk factors associated with substance use. ASSIST scores were used to categorize patients into drug risk groups. Mortality information from the National Death Index was used to calculate mortality rates from 2009 to 2012. A Cox regression model identified associations between drug risk groups and mortality while controlling for patient demographics. The use of cocaine and cannabis both individually and in combination was associated with significantly higher mortality risk compared with other ED patients. ED patients who use cannabis and cocaine have higher mortality risks than other patients. Further research is necessary to determine whether this result is stable across racial/ethnic groups.


Detection of cytomegalovirus and Epstein-Barr virus in labial salivary glands in Sjogren's syndrome and non-specific sialadenitis.
To investigate the role of herpes viruses in Sjogren's syndrome, minor (labial) salivary gland tissues from Sjogren's syndrome and from non-specific sialadenitis were examined for Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) DNA by the polymerase chain reaction. Almost half of all salivary glands studied contained EBV and/or HCMV. There was, however, no significant difference between the detection of EBV or HCMV in salivary glands from patients with Sjogren's syndrome or non-specific sialadenitis. The findings are consistent with the persistence of EBV and HCMV in minor salivary glands following primary infection, but do not indicate a direct role for either virus in the aetiology of Sjogren's syndrome, and do not exclude reactivation of the viruses in this disease.


Bipolar spectrum: Relevant psychological and biological factors.
The bipolar spectrum is a concept which bridges bipolar I disorder and unipolar depression. As Kraepelin described, there may be continuity across mood disorders. If this is the case, why should we discriminate for drug choice For example, it is generally accepted that mood stabilizers should be used for the bipolar spectrum, whereas antidepressants are for unipolar depression. If these disorders are diagnostically continuous, it is possible that the same drug could be effective in treating both bipolar I disorder/spectrum and unipolar depression. To resolve this question, I would like to propose my hypothesis that there is an inflexion point which constitutes the boundary between the bipolar spectrum and unipolar depression. It is likely that this inflexion point consists of temperaments as, reportedly, there are many significant differences in the presence of various temperaments between the bipolar spectrum (bipolar II, II1/2 and IV) and unipolar depression. These findings suggest that temperaments could draw a boundary between the bipolar spectrum and unipolar depression. Moreover, it has been shown that certain temperaments may be associated with several biological factors and may be associated with drug response. As such, whilst the concept of the bipolar spectrum emphasizes continuity, it is the proposed inflexion point that discriminates drug responses between the bipolar spectrum and unipolar depression. At the moment, although hypothetical, I consider this idea worthy of further research.


Effects of medium-chain triaclyglycerol ingested with carbohydrate on metabolism and exercise performance.
The effects of ingesting different amounts of medium-chain triacylglycerol (MCT) and carbohydrate (CHO) on gastric symptoms, fuel metabolism, and exercise performance were measured in 9 endurance-trained cyclists. Participants, 2 hr after a standardized lunch, cycled for 2 hr at 63% of peak oxygen consumption and then performed a simulated 40-km time trial (Ttrial). During the rides, participants ingested either 10% 14C-glucose (GLU), 10% 14C-GLU + 1.72% MCT (LO-MCT), or 10% 14C-GLU +3.44% MCT (HI-MCT) solutions: 400 ml at the start of exercise and then 100 ml every 10 min. MCT ingestion did not affect gastrointestinal symptoms. It only raised serum free fatty acid (FFA) and beta-hydroxybutyrate concentrations. Higher FFA and beta-hydroxybutyrate concentrations with MCT ingestion did not affect fuel oxidation or T-trial performance. The high CHO content of the pretrial lunch increased starting plasma insulin levels, which may have promoted CHO oxidation despite elevated circulating FFA concentrations with MCT ingestion.


[Interprofessional Collaborative Practice in Long-Term Care: Swallow Training].
Oropharyngeal dysphagia is common in elders living in long-term care facilities. Nasogastric tubes are used in place of normal eating when severe swallowing disorders affect oral intake. Swallowing training is usually delivered by a speech therapist who uses different food textures for training at different stages, depending on the severity and progression of the disorder. The amount and texture of foods are adjusted by the dietitian based on an elder's ability to eat. The current care model allows the specific preferences and experiences of the implementing specialist to guide delivery of swallowing training and thus lacks comprehensive discussion and planning, which may result in interventions failing to achieve their expected effect. In this study, we discuss how to implement the professional integration of dietitians and speech therapists, set goals for nutrition improvement and safe oral eating for the elderly with swallowing disorders in long-term care facilities. Swallowing training protocols and diet for each stage, texture adjustment, design, and caregiver guidance to prepare quantitative diets are provided to enhance the effectiveness of swallowing training. It is expected that implementation of the holistic care model presented in this study will improve quality of life in patients with oropharyngeal dysphagia, meet the expectations of both patients and family members, and help realize the professional core value of "case-centered".


[Late results of radiotherapy of soft tissue sarcoma].
To evaluate the effect of radiation therapy in the treatment of soft-tissue sarcomas. Between March 1970 and January 1990, 58 patients with soft-tissue sarcoma were referred for radiation therapy. The most frequent histologic diagnoses included fibrosarcoma (n = 15), neurofibrosarcoma (n = 5) and rhabdomyosarcoma (n = 5). Central tumor sites in the trunk (n = 31) were much more frequent than in the head and neck region (n = 14) or the extremities (n = 13). Thirty-nine of 58 primary tumors were bigger than 5 centimeters. Forty-five patients were irradiated after surgery, 5 patients prior to surgery; in 8 cases only radiation therapy was used. Radiation therapy was performed with Co-60 photons and an average total dose of 58 Gy, fractionated in single doses of 2 Gy. The treatment results were obtained by actual follow-up examinations. Twenty-three of 58 patients survived at least 5 years (39.9%). Of 15 patients with R0 resection 11 were alive after 5 years (73.3%). Local tumor control was achieved in 34 of 58 patients (58.6%). Low 5-year-survival rates were associated with dedifferentiation of the primary tumor (three survivors in 10 patients with G3 tumor), tumor diameters over 5 cm (13 survivors of 39), R2 resection (3 survivors of 16) and tumor sites in the body trunk (11 survivors of 31). (1) The best results of radiation therapy were achieved after R0 resection of the primary tumor. (2) Tumors in the trunk are prognostically worse because of bigger tumor diameters due to later diagnosis.


Evaluation of antimicrobial activity against Enterococcus faecalis of activated chelating agents in different final rinse protocols: An ex vivo study.
To evaluate the antimicrobial activity of the following chelating agents against Enterococcus faecalis using quantitative polymerase chain reaction (qPCR) analysis: 1% peracetic acid (PA), 1% peracetic acid with 0.1% cetrimide (PAC), and 17% ethylenediaminetetraacetic acid (EDTA) activated by passive ultrasonic irrigation (PUI) or with Easy Clean (EC), all followed by 2.5% sodium hypochlorite (NaOCl). A total of 80 permanent human mandibular premolars were randomly divided into eight experimental groups according to the chemical solution and agitation protocol used: Group PA + PUI; Group PA + EC; Group PAC + PUI; PAC + EC; group EDTA + PUI; EDTA + EC, all followed by 2.5% NaOCl; and two control groups with saline solution(NaCl): NaCl + PUI and NaCl + EC. Microbial samples were collected before (S1) and after the irrigation protocol (S2). Intracanal E. faecalis reduction analysis was performed by qPCR. Intragroup analysis was performed using the Wilcoxon signed-rank test for paired data, and intergroup analysis was performed using the Wilcoxon Mann-Whitney U test for independent samples. The significance level was set at p< 0.05. A significant difference was found between S1 and S2 in all groups except NaCl+ EC (p = 0.1602). Comparison between groups showed that PAC + PUI was significantly different from PA +EC (p = 0.0448). The activated chelating agents were effective against E. faecalis, with significant results compared to the control groups. The peracetic acid with cetrimide activated by PUI showed better results than peracetic acid with EC. Key words:Easy clean, Final irrigation protocols, Passive ultrasonic irrigation, Peracetic acid.


Histologic change of the meniscus and cartilage tissue after meniscal suture.
The influence of suturing on cell infiltration into the meniscus and surrounding tissue is not well known. Histologic changes in the meniscus after suturing and prediction of histologic changes using magnetic resonance imaging were studied. Forty knees in 20 mongrel dogs were studied using four types of 4-0 suture material: nonabsorbable monofilament, nonabsorbable braided, absorbable monofilament, and absorbable braided. Each type of suture material was used for meniscal suture on eight knees each. The other eight knees were not subjected to meniscal suture. Specimens obtained at 1 and 3 months were studied by magnetic resonance imaging and light microscopic analysis. The maximum width of change of meniscal tissue was measured. Changes from the nonabsorbable suture group were smaller than that of the absorbable suture group in magnetic resonance imaging. Histologic changes as seen by light microscope were larger in the absorbable group than in the nonabsorbable group at 1 and 3 months after surgery. Injury was found in the articular cartilage of the femoral condyle in the nonabsorbable braided suture group. Histologic changes were significantly greater when changes in magnetic resonance imaging signal intensity were larger. The current study showed that non-absorbable monofilament suture material results in the least damage to the meniscus and surrounding tissue.


Seven steps for qualitative treatment in health research: the Clinical-Qualitative Content Analysis.
Qualitative Health research procedures that are not always applied, mainly in the analysis phase. Our objective is to present a systematized technique of step-by-step procedures for qualitative content analysis in the health field: Clinical-Qualitative Content Analysis. Our proposal consider that the qualitative research applied to the field of health, can acquire a perspective analogous to clinical practice and aims to interpret meanings expressed in reports through individual interviews or statements. This analysis takes part of the Clinical-Qualitative Method. The literature review was realized through: a book chapter, eight original articles and three methodological articles. The Clinical-qualitative Content Analysis technique comprises seven steps: 1) Editing material for analysis; 2) Floating reading; 3) Construction of the units of analysis; 4) Construction of codes of meaning; 5) General refining of the codes and the Construction of categories; 6) Discussion; 7) Validity. The clinical-qualitative analysis presupposes and involves a critical reflection on the processes carried out at each step. This reflection is an extremely rich process, if carried out collectively and in dialogue with other researchers with some proficiency in qualitative methods.


Collegiate year of eligibility, sex, and sports achievement motivation.
The relations among year of eligibility, sex, and achievement motivation were investigated with 88 athletes representing three levels of collegiate eligibility (Year 1, Year 2/3, and Year 4) by sex. Participants were given Achievement Motivation subscales for Sporting Environments (approach-success practice, approach-success competition, failure-avoidance practice, failure-avoidance competition). A 3 x 2 analysis of variance showed significant main effects for year of eligibility and sex, and an interaction for age x sex for the failure-avoidance competition scores. Mean approach-success and failure-avoidance practice scores were not significantly different. Fear of failure may be less for male athletes in Year 4 of eligibility.


From stable divalent to valence-fluctuating behaviour in Eu(Rh(1-x)Ir(x))2Si2 single crystals.
We have succeeded in growing high-quality single crystals of the valence-fluctuating system EuIr(2)Si(2), the divalent Eu system EuRh(2)Si(2) and the substitutional alloy Eu(Rh(1-x)Ir(x))(2)Si(2) across the range 0 < x < 1, which we characterized by means of x-ray diffraction, energy-dispersive x-ray spectroscopy, specific heat, magnetization and resistivity measurements. On increasing x, the divalent Eu ground state subsists up to x = 0.25 with a slight increase in Néel temperature, while for 0.3≤x < 0.7 a sharp hysteretic change in susceptibility and resistivity marks the first-order valence transition. For x≳0.7 the broad feature observed in the physical properties is characteristic of the continuous valence evolution beyond the critical end point of the valence transition line, and the resistivity is reminiscent of Kondo-like behaviour while the Sommerfeld coefficient indicates a mass renormalization of at least a factor of 8. The resulting phase diagram is similar to those reported for polycrystalline Eu(Pd(1-x)Au(x))(2)Si(2) and EuNi(2)(Si(1-x)Ge(x))(2), confirming its generic character for Eu systems, and markedly different to those of homologue Ce and Yb systems, which present a continuous suppression of the antiferromagnetism accompanied by a very smooth evolution of the valence. We discuss these differences and suggest them to be related to the large polarization energy of the Eu half-filled 4f shell. We further argue that the changes in the rare earth valence between RRh(2)Si(2) and RIr(2)Si(2) (R = Ce, Eu, Yb) are governed by a purely electronic effect and not by a volume effect.


Using ratiometric indicator-displacement assays in semi-quantitative colorimetric determination of chloride, bromide, and iodide anions.
A ratiometric indicator-displacement assay (RIDA) array has been developed for the semi-quantitative colorimetric determination of chloride, bromide, and iodide anions. Determinations of these halide anions follow the displacement reaction using the chelate compound of (2-(3,5-dibromo-2-pyridylazo)-5-(diethylamino)phenol) (3,5-Br2-PADAP) and heavy metal salts as colorimetric reagent. Different from regular silver nitrate titrations, the chloride, bromide, and iodide anions compete with the 3,5-Br2-PADAP ligand and change the colour of the 3,5-Br2-PADAP-metal chelate compound dramatically. These clearer colour changes make the semi-quantitative colorimetric determination of chloride, bromide, and iodide anions possible. The colour changes are imaged using a conventional flatbed scanner, and digitized. After statistical analysis, these colour changes in the RIDA array provide facile identification of chloride, bromide, and iodide anions at a wide concentration range (10 μM to 10 mM) without any misclassification. The RIDA array is able to discriminate without misclassifications among seven concentrations of chloride, bromide, and iodide anions. No shelf life issue exists because the chelating compounds react with halide anions directly without any pre-immobilizations.


QSAR's based on partial order ranking.
The development of Quantitative Structure Activity Relationships (QSAR's) often relies heavily on the application of statistical methods such as multi-linear regression (MLR) or principal component analysis/partial least square (PCA/PLS). Partial order ranking (POR), which from a mathematical point of view is based on elementary methods of Discrete Mathematics, appears as an attractive and operationally simple and more general alternative since the method does not require specific functional relationships between the single descriptors or the end-points. The POR method allows ranking of a series of compounds, based on selected descriptors characterizing their structural and/or electronic nature (model diagram). The ranking of the compounds based on their end-points (experimental ranking) can then be compared to the model diagram. If the model diagram resembles the experimental ranking of the end-points under investigation, other compounds, not being experimentally investigated, can be assigned a rank in the model and hereby obtain an identity based on the known compounds. The present study elucidates the applicability of POR as a simple tool for QSAR modeling. Based on illustrative examples the POR approach to QSAR modeling will be presented with special focus on the precision and the uncertainties of the method, which will be discussed in terms of the number of descriptors and compounds involved. The advantageous interplay between POR and PCA, the latter being applied in order to reduce a possible large number of descriptors into a limited number of latent descriptors will be discussed.


Isosakuranetin-5-O-rutinoside: a new flavanone with antidepressant activity isolated from Salvia elegans Vahl.
Ursolic acid (1) and a new flavanone, 5-O-(6-rhamnosylglucoside)-7-hydroxy-4'-methoxyflavanone (2), were isolated from the leaves of Salvia elegans Vahl. These natural products displayed antidepressant activity in mice as determined by means of a forced swimming test (FST) evaluation. Structural elucidation was carried out by chemical derivatization (acetylation) and spectroscopic analyses, such as 1H- and 13C-NMR and two-dimensional (2-D) COSY, heteronuclear multiple quantum coherence (HMQC), and heteronuclear multiple-bond correlation (HMBC) spectroscopy experiments.


Mechanisms of viral interference with MHC class I antigen processing and presentation.
Viruses are ubiquitous and dangerous obligate intracellular parasites. To facilitate recognition of virus-infected cells by the immune system, vertebrates evolved a system that displays oligopeptides derived from viral proteins on the surface of cells in association with class I molecules of the major histocompatibility complex. Here we review the mechanisms counter-evolved by viruses to interfere with the generation of viral peptides, their intracellular trafficking, or the cell surface expression of class I molecules bearing viral peptides. This topic is important in its own right because the viruses that encode these proteins represent medically important pathogens, are potential vectors for vaccines or gene therapy, and provide strategies and tools for blocking immune recognition in transplantation, autoimmunity, and gene therapy. In addition, studies on viral interference provide unique insights into unfettered antigen processing and normal cellular functions that are exploited and exaggerated by viruses.


Characteristics of Lung Microbiota in Children's Refractory Mycoplasma pneumoniae Pneumonia Coinfected with Human Adenovirus B.
Both M. pneumoniae and human adenovirus (HAdV) are common causative agents of lower respiratory tract infection in children; nonetheless, the lung microbiota in patients with coinfection of HAdV and M. pneumoniae remain unexplored. Thirty-two children, diagnosed with refractory M. pneumoniae pneumonia (RMPP), entered into the one-year study from July 1, 2019 to June 30, 2020. Among them, twenty-one entered into the M. pneumoniae monoinfection (MP) group and eleven entered into the M. pneumoniae and HAdV coinfection (MP&ADV) group. The characteristics of the clinical findings were examined, and the lung microbiota was analyzed by metagenomic next generation sequencing (mNGS). Eleven patients in the MP&ADV group were coinfected with human mastadenovirus species B. The fever days lasted for significantly longer periods in the MP&ADV group than in the MP group (P < 0.05). The percentage of CD16+CD56+ cells was significantly higher in the MP&ADV group than that in the MP group (P < 0.05). There were no significant differences in α-diversity between the MP and MP&ADV groups, but the β-diversity was clearly higher in the MP&ADV group than that in the MP group (P < 0.05). At the microbial level, the top phylum of the MP BALF microbiota was Tenericutes; in contrast, it was Preplasmiviricota in the MP&ADV BALF. There were significant differences in the relative abundance of Tenericutes and Preplasmiviricota between the two groups (P < 0.001). There was a strong positive correlation between human mastadenovirus B and fever days, M. pneumoniae and level of IgA, and a strong negative correlation between Mycoplasma pneumoniae and PCT. In RMPP, the BALF microbiota in children with mono M. pneumoniae infection was simpler than those with coinfection with human mastadenovirus B. Prolonged fever days were associated with human mastadenovirus B coinfection.