Longitudinal changes in young children's strategy use for emotion regulation.
The development of strategies that support autonomous self-regulation of emotion is key for early childhood emotion regulation. Children are thought to transition from predominant reliance on more automatic or interpersonal strategies to reliance on more effortful, autonomous strategies as they develop cognitive skills that can be recruited for self-regulation. However, there are few longitudinal studies documenting age-related changes in different forms and dimensions of strategies. The current study tested predicted age-related changes in strategy use in a task requiring children to wait for something they want. Specifically, we examined the longitudinal trajectories of 3 strategies commonly observed in delayed reward tasks: self-soothing, seeking attention about the demands of waiting (bids), and distracting oneself. We followed a sample of 120 children (54% male, 93.3% white, from semirural and rural economically strained households) from ages 24 months to 5 years who participated in a waiting task each year. Using growth curve modeling, we found declines in self-soothing, rises and then declines in bidding, and increases in distraction from 24 months to 5 years. Next, we investigated whether strategy use trajectories predicted adult ratings of children's emotion regulation during the task, that is, whether children appeared calm and acted appropriately while waiting. Growth in duration and dominance of distraction use predicted judgments that children were well-regulated by age 5 years, whereas growth in dominance of bidding use negatively predicted being rated as well-regulated. We discuss implications for the understanding of strategy development and future directions, including understanding strategy effectiveness. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Comparison of the oligosaccharide moieties of the major envelope glycoproteins of the subgroup A and subgroup B avian myeloblastosis-associated viruses.
The nature of the oligosaccharide chains of the major envelope glycoprotein, gp85, from avian myeloblastosis-associated viruses has been examined for the subgroup A and subgroup B viruses replicated in fibroblasts from the same chicken embryos. Pronase-digested glycopeptides from [3H]mannose- or [3H]glucosamine-labeled viruses were analyzed by the combined techniques of gel filtration, endo-beta-N-acetylglucosaminidase digestion, and concanavalin A affinity chromatography. The gp85 protein from these two viruses, and also from another subgroup A avian leukosis virus replicated in the same cells, contained a diverse array of asparagine-linked oligosaccharides of the acidic type [(sialic acid +/- galactose-N-acetylglucosamine)2-4-(mannose)3-N-acetylglucosamine2(+/- fucose)-asparagine], hybrid type (sialic acid +/- galactose-N-acetylglucosamine-(mannose)5,4-N-acetylglucosamine2-asparagine), and neutral type [(mannose)5-9-N-acetylglucosamine2-asparagine], with the more highly branched (tri or tetraantennary or both) acidic-type structures representing the predominant class of oligosaccharide. Minor differences were observed between the gp85 of the subgroup B versus subgroup A viruses.


Epididymosomes convey different repertoires of microRNAs throughout the bovine epididymis.
Epididymosomes are small membrane vesicles that are secreted by epididymal epithelial cells and are involved in posttesticular sperm maturation. Although their role in protein transfer to the sperm membrane is well documented, we report their capacity to transport microRNAs (miRNAs), which are potent regulators of posttranscriptional gene expression. Using a microperfusion technique combined with a global microarray approach, we demonstrated that epididymosomes from two discrete bovine epididymal regions (caput and cauda) possess distinct miRNA signatures. In addition, we also established that miRNA repertoires contained within epididymosomes differ from those of their parent epithelial cells, suggesting that miRNA populations released from the cells may be selectively sorted. Binding of DilC12-labeled epididymosomes to primary cultured epididymal cells was measured by flow cytometry, and the results indicated that epididymosomes from the median caput and their miRNA content may be incorporated into distal caput epithelial cells. Overall, these findings reveal that distinct miRNA repertoires are released into the intraluminal fluid in a region-specific manner and could be involved in a novel mechanism of intercellular communication throughout the epididymis via epididymosomes.


Effects of incorporating calcined corals as natural antimicrobial agent into active packaging system for milk storage.
A series of nylon (NY)/linear low-density polyethylene (LLDPE) containing calcined corals (NY/LL-CORALS) composite films were prepared using the cast extrusion method. We investigated the effect of different contents of incorporated calcined corals on the physical properties and antimicrobial activity of the composite films as well as their feasibility for milk storage applications. The results indicated that the main compound in calcined corals was calcium oxide (CaO). As the calcined corals content increased, the crystallinity of the composite films slightly decreased, but no significant changes in their thermal stability and permeability were observed. The NY/LL-CORALS composite films exhibited excellent antimicrobial performance against Escherichia coli and Staphylococcus aureus. Notably, the NY/LL-CORALS packaging significantly extended the lag time of bacteria and delayed the bacterial growth cycle in milk during storage. Thus, the NY/LL-CORALS composite films could be a potential food packaging material that could prolong the shelf life of fresh food.


Splenic diffuse red-pulp small B-cell lymphoma associated with hepatitis B virus: a report of two cases.
Splenic diffuse red-pulp small B-cell lymphoma is a rare disease, representing less than 1% of all non-Hodgkin lymphomas (NHL). This entity is characterized by involvement of bone marrow sinusoids and peripheral blood. The majority of cases are at an advanced stage when diagnosed. Its pathogenesis is still poorly understood. We report on two patients with chronic non-replicating hepatitis B virus (HBV) who developed splenic diffuse red-pulp small B-cell lymphoma. Both of them were in stage IV at diagnosis and evolved with aggressive disease. Both of them achieved a complete response through chemotherapy, but one of them died due to infectious complications during bone marrow transplantation. The other decided not to undergo transplantation and continues not to show any evidence of disease today (three years after treatment). Some studies have shown a possible association between B-cell NHL and HBV. Nonetheless, the mechanism through which this oncogenic virus interacts with B-cell NHL is still poorly understood. HBV is lymphotropic and may insert into the host's genome, thus causing overexpression of oncogenes and downregulation of tumor suppressor genes. Therefore, chronic stimulation by HBV can increase B-cell proliferation, which promotes monoclonal expansion of these cells and results in malignancy. HBV may be implicated in the pathogenesis of this lymphoma, although no direct association between these two entities could be proved in the present study. Further investigations are necessary.


Screening a redox library identifies the anti-tumor drug Hinokitiol for treating intrahepatic cholangiocarcinoma.
Intrahepatic cholangiocarcinoma (ICC) is a highly malignant and heterogeneous cancer with a poor prognosis. At present, there is no optimal treatment except for surgical resection, and recurrence after resection will lead to death due to multidrug resistance. Changes in the redox signal have been found to be closely related to the growth and drug resistance of tumor cells. Therefore, the purpose of this study was to screen small molecule compounds from the redox library to find a drug for anti-ICC and to explore its downstream mechanism. Tumor clone and sphere formation of ICC cell lines, as well as mouse ICC organoid proliferation assays were utilized to screen the candidate drug in the Redox library. Western blotting, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), as well as cell apoptosis and cell cycle flow cytometry assays were used to explore the mechanism. We found that Hinokitiol was a candidate drug through inhibition of tumor clone and sphere formation, and the expression of cancer stem cell (CSC)-related genes. Furthermore, Hinokitiol significantly inhibited the proliferation of ICC cells by downregulating the ERK and P38 pathways. In addition, the combination of Hinokitiol and Palbociclib showed a significant inhibitory effect on human ICC cells and mouse ICC organoids. Hinokitiol may have the potential to be developed as a clinical therapeutic drug for ICC treatment.


Identification and kinetics of leukocytes after severe ischaemia/reperfusion renal injury.
Leukocyte adhesion/infiltration in response to renal ischaemia/reperfusion (I/R) injury is a well-known but poorly understood phenomenon. The identification, kinetics, and exact role of these inflammatory cells in I/R injury and regeneration are still matters of debate. Uninephrectomized rats were submitted to 60 min renal ischaemia by clamping of renal vessels. Severe acute renal failure was observed, with maximum functional impairment on day 2. By 12 h after the ischaemic event, up to 80% of proximal tubular cells in the outer stripe of outer medulla (OSOM) were already severely damaged. Proliferation (proliferating cell nuclear antigen (PCNA) staining) started after 24 h, reaching maximum activity on day 3. Regeneration of tubular morphology started on the 3rd day, and after 10 days 50% of tubules had regenerated completely. Interstitial leukocytes (OX-1 immunohistochemical staining) were already prominent at day 1, thereafter gradually increasing with time. The so-called neutrophil-specific identification methods (myeloperoxidase (MPO), chloroacetate esterase, mAb HIS-48) proved to be non-specific, since they also stained for macrophages, as demonstrated by flow cytometry and the combination of these stainings with the macrophage-specific ED-1 staining. MPO activity was already significantly increased at 1 h post-I/R (439+/-34%, P<0.005), reaching its maximum activity after 12 h of I/R (1159+/-138%, P<0.0005), declining thereafter. On the other hand, neutrophil presence investigated by H&E staining revealed only a few neutrophils in glomeruli, medullary rays, and OSOM at 24 h after the ischaemic event (4.7+/-4.2 cells/mm(2) vs controls=2.3+/-2.0 cells/mm(2) (n.s.)), and remained unchanged over the next 10 days. In contrast, significant monocyte/macrophage adhesion/infiltration (ED-1 staining) occurred at the OSOM at 24 h post-ischaemia (at 24 h, 120+/-46 cells/mm(2) vs. sham=18+/-4 cells/mm(2) (P<0.05)), became prominent at day 5 (1034+/-161 cells/mm(2) vs sham=18+/-18 cells/mm(2) (P<0.05)), and almost disappeared after 10 days. CD4(+) cells (W3/25) gradually increased from day 5, reaching a maximum at day 10. A few CD8(+) cells (OX-8) were apparent from days 3 until 10, but no B-cells (OX-33) were observed. After severe warm I/R renal injury, a pronounced acute tubular necrosis occurs during the first 12-24 h in the absence of a marked cellular infiltrate, but with an important renal MPO activity, reflecting the activation of the adhering inflammatory cells (polymorphonuclear cells (PMNs) and mainly monocytes/macrophages). Only later at the time and site (OSOM) of regeneration a sequential accumulation of monocytes/macrophages and T cells becomes prominent, in contrast with the low number of neutrophils found in the kidney during the 10-day post-ischaemic period. The non-specificity of the so-called neutrophil-specific identification methods (MPO activity, naphthol AS-D chloroacetate esterase, or mAb HIS-48 staining), cross-reacting with monocytes/macrophages, explains the controversy in literature concerning the number of PMNs in post-ischaemic injury.


From the neuromatrix to the pain matrix (and back).
Pain is a conscious experience, crucial for survival. To investigate the neural basis of pain perception in humans, a large number of investigators apply noxious stimuli to the body of volunteers while sampling brain activity using different functional neuroimaging techniques. These responses have been shown to originate from an extensive network of brain regions, which has been christened the Pain Matrix and is often considered to represent a unique cerebral signature for pain perception. As a consequence, the Pain Matrix is often used to understand the neural mechanisms of pain in health and disease. Because the interpretation of a great number of experimental studies relies on the assumption that the brain responses elicited by nociceptive stimuli reflect the activity of a cortical network that is at least partially specific for pain, it appears crucial to ascertain whether this notion is supported by unequivocal experimental evidence. Here, we will review the original concept of the "Neuromatrix" as it was initially proposed by Melzack and its subsequent transformation into a pain-specific matrix. Through a critical discussion of the evidence in favor and against this concept of pain specificity, we show that the fraction of the neuronal activity measured using currently available macroscopic functional neuroimaging techniques (e.g., EEG, MEG, fMRI, PET) in response to transient nociceptive stimulation is likely to be largely unspecific for nociception.


[Outstanding Ukrainian phyto-therapist Danylo Zubyts'kyĭ].
The article presents data on phytotherapeutist, Daniel Zubitsky, an outstanding person in the field of folk medicine. He developed phytomedications for prevention and treatment of many diseases. Efficiency of phytomedications is proved through long-term practice of their use and positive responses of many patients.


The Association between the Regular Use of ICT Based Mobility Services and the Bicycle Mode Choice in Tehran and Cairo.
Regarding the sharp growth rate of ICT (information and communication technology) - based mobility services like ridesourcing, it is essential to investigate the impact of these new mobility services on the transport mode choices, particularly on active mobility modes like cycling. This impact is more important in the MENA context (the Middle East and North Africa), where cycling does not constitute the main mobility mode in the modal split of most MENA cities. This paper studies the relationship between the regular use of ICT-based mobility services like ridesourcing and the tendency to cycle to near destinations. This paper contains the analysis of 4431 interviews in two large cities of the MENA region (Cairo and Tehran). This research uses logistic regression to analyze and compare the odds of cycling among regular and non-regular users of ridesourcing by considering the socio-economic, land use, and perception variables. The findings indicate that the odds of cycling among the regular users of ridesourcing are 2.30 and 1.94 times greater than these odds among non-regular ridesourcing users in Tehran and Cairo, respectively. Therefore, the regular users of ridesourcing are more likely to cycle to their near destinations than non-regular ridesourcing users in these cities.


Latino Family Participation in Youth Mental Health Services: Treatment Retention, Engagement, and Response.
Although researchers have identified a multitude of factors that contribute to family participation in mental health services, few studies have examined them specifically for Latino youth and their families in the U.S., a population that continues to experience significant disparities related to the availability, accessibility, and quality of mental health services. Latino youth and their families are at greater risk of dropping out of treatment prematurely and demonstrating poor treatment engagement, both of which have subsequent negative effects on treatment response outcomes. In order to help to guide efforts to improve the accessibility and quality of mental health services for Latino youth and their families, the current paper integrates modern conceptualization of family participation in youth mental health services and provides a summary of contextual factors within an ecological framework (Bronfenbrenner in The ecology of human development: experiments by nature and design, Harvard University Press, Cambridge, 1979). The current review aims to integrate empirical research on the impact of various contextual factors across multiple levels (i.e., culture, community, mental health system, family, parent/caregiver, and child/adolescent) on Latino family participation in youth mental health services, including treatment retention, engagement, and response. Clinical implications will be discussed, and an integrated, conceptual model will be presented. Not only does this model help to demonstrate the way in which existing literature is conceptually linked, but it also helps to highlight factors and underlying processes that health care providers, administrators, and policy makers must consider in working to improve mental health services for Latino youth and their families living in the U.S.


Prediction of Poly(A) Sites by Poly(A) Read Mapping.
RNA-seq reads containing part of the poly(A) tail of transcripts (denoted as poly(A) reads) provide the most direct evidence for the position of poly(A) sites in the genome. However, due to reduced coverage of poly(A) tails by reads, poly(A) reads are not routinely identified during RNA-seq mapping. Nevertheless, recent studies for several herpesviruses successfully employed mapping of poly(A) reads to identify herpesvirus poly(A) sites using different strategies and customized programs. To more easily allow such analyses without requiring additional programs, we integrated poly(A) read mapping and prediction of poly(A) sites into our RNA-seq mapping program ContextMap 2. The implemented approach essentially generalizes previously used poly(A) read mapping approaches and combines them with the context-based approach of ContextMap 2 to take into account information provided by other reads aligned to the same location. Poly(A) read mapping using ContextMap 2 was evaluated on real-life data from the ENCODE project and compared against a competing approach based on transcriptome assembly (KLEAT). This showed high positive predictive value for our approach, evidenced also by the presence of poly(A) signals, and considerably lower runtime than KLEAT. Although sensitivity is low for both methods, we show that this is in part due to a high extent of spurious results in the gold standard set derived from RNA-PET data. Sensitivity improves for poly(A) sites of known transcripts or determined with a more specific poly(A) sequencing protocol and increases with read coverage on transcript ends. Finally, we illustrate the usefulness of the approach in a high read coverage scenario by a re-analysis of published data for herpes simplex virus 1. Thus, with current trends towards increasing sequencing depth and read length, poly(A) read mapping will prove to be increasingly useful and can now be performed automatically during RNA-seq mapping with ContextMap 2.


Anti-myeloperoxidase and anti-cathepsin G antibodies in sulphonamide hypersensitivity.
Anti-neutrophil cytoplasmic antibodies (ANCA) are associated with vasculitis in humans. Sulphonamide antimicrobials cause drug hypersensitivity (HS) reactions with some clinical signs that are suggestive of vasculitis. The purpose of this study was to determine whether sulphonamide HS is associated with anti-neutrophil antibodies, using the dog as a spontaneous clinical model. Thirty-four sulphonamide-HS dogs, 11 sulphonamide-'tolerant' dogs, and nine healthy sulphonamide-naïve dogs were evaluated for anti-neutrophil antibodies using a commercial ELISA against human myeloperoxidase (MPO), a commercial human ANCA Western blot protocol, and immunoblotting against whole canine neutrophils. Using ELISA, anti-MPO antibodies were found with an apparent higher frequency in HS dogs (50%), compared with 'tolerant' dogs (18%), which also showed significantly lower absorbances. Among HS dogs, anti-MPO antibodies were significantly more common, with significantly higher absorbances, in dogs that did not survive the HS reaction (78%) compared with survivors (35%). Using immunoblotting, ANCA were detected with similar overall frequencies in HS and 'tolerant' dogs. However, one protein targeted by several HS dogs, but no 'tolerant' dogs, was identified as cathepsin G. These data indicate that anti-MPO antibodies and anti-cathepsin G antibodies are associated with sulphonamide HS. Anti-MPO antibodies have been shown to be pathogenic both in vitro and in vivo, leading to vasculitis lesions and vasculitis-like syndromes. The present study therefore suggests that vasculitis might be one mechanism of tissue damage in this sulphonamide HS. Furthermore, the evaluation of ANCA, and its relationship to disease severity and clinical outcome, should be considered in human patients with sulphonamide drug HS.


Effects of nebivolol on artery hypertension--multicentre study Bosnia and Herzegovina.
Hypertension is a major risk factor for cardiovascular diseases; drugs that reduce blood pressure and simultaneously improve or reverse endothelian dysfunction, as nebivolol, may be advantageous in terms of cardiovascular protection. The objective of this study is to show the anti-hypertensive efficacy and safety of nebivolol (5 mg once a day) given to patients with arterial hypertension for 3 months. It should also provide information about drug's influence on laboratory tests--fasting blood glucose and serum cholesterol, triglyceride and creatinine concentrations. Six centers--Tuzla, Sarajevo, Mostar, Bihac, Zenica and Banja Luka participated in this prospective study with follow-up period of 3 months that included 3 visits. The study group consisted of 328 hypertensic patients. Results showed a significant decrease in both systolic and diastolic blood pressure and heart rate at the end of the study. Fasting blood glucose level and serum cholesterol, triglyceride and creatinine changed significantly during the study, with lower levels of all the tests. Nebivolol seems to be free from some of the problems that generally accompany not only the classical beta- blockers but sometimes also newer classes of antihypertensive drugs. With its high anti-hypertensive efficiency and safety, and presence of statically significant difference in laboratory tests and beneficial effects, absence of adverse interaction with glucose and lipid metabolism, patients treated with Nebivolol may show an optimal adherence to therapy.


Parametric estimation of the orientation of textured planar surfaces.
This paper presents a parametric solution to the problem of estimating the orientation in space of a planar textured surface, from a single, noisy, observed image of it. The coordinate transformation from surface to image coordinates, due to the perspective projection, transforms each homogeneous sinusoidal component of the surface texture into a sinusoid whose frequency is a function of location. The functional dependence of the sinusoid phase in location is uniquely determined by the tilt and slant angles of the surface. Using the phase differencing algorithm we fit a polynomial phase model to a sinusoidal component of the observed texture. Assuming the estimated polynomial coefficients are the coefficients of a Taylor series expansion of the phase, we establish a linear recursive relation between the model parameters and the unknown slant and tilt. A linear least squares solution of the resulting system provides the slant and tilt estimates. To improve accuracy, an iterative refinement procedure is applied in a small neighborhood of these estimates. The performance of the proposed algorithms is evaluated by applying them to images of different planar surfaces, and by comparing their statistical performance with the Cramer-Rao bound. The combined two-stage algorithm is shown to produce estimates that are close to the bound.


Ferredoxin:thioredoxin reductase (FTR) links the regulation of oxygenic photosynthesis to deeply rooted bacteria.
Uncovered in studies on photosynthesis 35 years ago, redox regulation has been extended to all types of living cells. We understand a great deal about the occurrence, function, and mechanism of action of this mode of regulation, but we know little about its origin and its evolution. To help fill this gap, we have taken advantage of available genome sequences that make it possible to trace the phylogenetic roots of members of the system that was originally described for chloroplasts-ferredoxin, ferredoxin:thioredoxin reductase (FTR), and thioredoxin as well as target enzymes. The results suggest that: (1) the catalytic subunit, FTRc, originated in deeply rooted microaerophilic, chemoautotrophic bacteria where it appears to function in regulating CO(2) fixation by the reverse citric acid cycle; (2) FTRc was incorporated into oxygenic photosynthetic organisms without significant structural change except for addition of a variable subunit (FTRv) seemingly to protect the Fe-S cluster against oxygen; (3) new Trxs and target enzymes were systematically added as evolution proceeded from bacteria through the different types of oxygenic photosynthetic organisms; (4) an oxygenic type of regulation preceded classical light-dark regulation in the regulation of enzymes of CO(2) fixation by the Calvin-Benson cycle; (5) FTR is not universally present in oxygenic photosynthetic organisms, and in certain early representatives is seemingly functionally replaced by NADP-thioredoxin reductase; and (6) FTRc underwent structural diversification to meet the ecological needs of a variety of bacteria and archaea.


Predictive modelling in paleoenvironmental reconstruction: The micromammals of Manot Cave, Israel.
This paper describes the micromammalian remains and paleoenvironment of the Upper Paleolithic sequence of Manot Cave (46-34 ka), southern Levant. Micromammal remains were identified from Ahmarian (46-42 ka), Levantine Aurignacian (38-34 ka) and post-Levantine Aurignacian (34-33 ka) layers. To identify taphonomic agents, molar digestion was modelled for seven local raptor species, and model predictions were compared with observed digestion scores in the Manot Cave material. Raptor species differed significantly in molar digestion patterns, allowing us to identify Tyto alba as the bone accumulator in the Ahmarian and Post-Levantine Aurignacian units. Data were insufficient for species-level identification of the taphonomic agent in the Levantine Aurignacian. Günther's voles (Microtus guentheri) were dominant, though woodland species (Apodemus spp., Sciurus anomalus and Dryomys nitedula) also occurred through the entire sequence. Manot Cave furnished the first fossil record of the Eurasian snow vole (Chionomys nivalis) in the southern Levant during the Late Pleistocene and its first secure record of the water vole (Arvicola terrestris) outside the Hula Valley. Records of other taxa (Acomys dimidiatus and D. nitedula) provide the earliest occurrence datum in the region. Using counts of both identified specimens and distinct elements (lower first molars) we modelled paleoenvironmental conditions through both Weighted Averaging Partial Least Squares regression and a qualitative analysis considering niche preferences of species. Model predictions indicate the unexpectedly pronounced dominance of open habitats compared to present conditions near the cave, though the occurrence and abundance of woodland species also indicate some woodland expansion relative to the preceding Middle Paleolithic period. Combining statistical models and species niche considerations we show that the time span between the Ahmarian, Levantine Aurignacian and post-Levantine Aurignacian was marked by a clear-cut climatic oscillation to cooler and likely wetter conditions.


[Evaluation on contribution rate of each component total salvianolic acids and characterization of apparent oil/water partition coefficient].
The difference between three representative components of total salvianolic acids in pharmacodynamic activity were compared by three different pharmacological experiments: HUVECs oxidative damage experiment, 4 items of blood coagulation in vitro experiment in rabbits and experimental myocardial ischemia in rats. And the effects of contribution rate of each component were calculated by multi index comprehensive evaluation method based on CRITIC weights. The contribution rates of salvianolic acid B, rosmarinic acid and Danshensu were 28.85%, 30.11%, 41.04%. Apparent oil/water partition coefficient of each representative components of total salvianolic acids in n-octyl alcohol-buffer was tested and the total salvianolic acid components were characterized based on a combination of the approach of self-defined weighting coefficient with effects of contribution rate. Apparent oil/water partition coefficient of total salvianolic acids was 0.32, 1.06, 0.89, 0.98, 0.90, 0.13, 0.02, 0.20, 0.56 when in octanol-water/pH 1.2 dilute hydrochloric acid solution/ pH 2.0, 2.5, 5.0, 5.8, 6.8, 7.4, 7.8 phosphate buffer solution. It provides a certain reference for the characterization of components.


Precipitation, Climate Change, and Parasitism of Prairie Dogs by Fleas that Transmit Plague.
Fleas (Insecta: Siphonaptera) are hematophagous ectoparasites that can reduce the fitness of vertebrate hosts. Laboratory populations of fleas decline under dry conditions, implying that populations of fleas will also decline when precipitation is scarce under natural conditions. If precipitation and hence vegetative production are reduced, however, then herbivorous hosts might suffer declines in body condition and have weakened defenses against fleas, so that fleas will increase in abundance. We tested these competing hypotheses using information from 23 yr of research on 3 species of colonial prairie dogs in the western United States: Gunnison's prairie dog (Cynomys gunnisoni, 1989-1994), Utah prairie dog (Cynomys parvidens, 1996-2005), and white-tailed prairie dog (Cynomys leucurus, 2006-2012). For all 3 species, flea-counts per individual varied inversely with the number of days in the prior growing season with >10 mm of precipitation, an index of the number of precipitation events that might have caused a substantial, prolonged increase in soil moisture and vegetative production. Flea-counts per Utah prairie dog also varied inversely with cumulative precipitation of the prior growing season. Furthermore, flea-counts per Gunnison's and white-tailed prairie dog varied inversely with cumulative precipitation of the just-completed January and February. These results complement research on black-tailed prairie dog (Cynomys ludovicianus) and might have important ramifications for plague, a bacterial disease transmitted by fleas that devastates populations of prairie dogs. In particular, our results might help to explain why, at some colonies, epizootics of plague, which can kill >95% of prairie dogs, are more likely to occur during or shortly after periods of reduced precipitation. Climate change is projected to increase the frequency of droughts in the grasslands of western North America. If so, then climate change might affect the occurrence of plague epizootics among prairie dogs and other mammalian species that associate with them.


Feasibility, safety, and efficacy of iron bioresorbable scaffold in neonates with duct-dependent pulmonary circulation.
Bioresorbable stent has the theoretical advantage in the pediatric age group; however, experience in the literature is very limited. This pilot study sought to evaluate the feasibility, safety, and performance of iron bioresorbable scaffold (IBS Angel™) as short-term palliation in lesions with noncomplex patent ductus arteriosus (PDA). Nine neonates with duct dependent but dual-source pulmonary blood flow (PBF) were included. Major stent-related complications, in-hospital course, stent patency up to 6 months, and unplanned re-interventions were studied, as well the percentage of stent material resorbed in patients in whom the stents were explanted at the surgery. IBS Angel™ was successfully implanted in all nine patients (mean weight range 3.4 ± 0.4 kg). Six were pulmonary atresia with an intact ventricular septum and 1 critical pulmonary stenosis patients where PDA stenting was done together or after balloon dilation. The mean procedure and fluoroscopy times were 89 ± 39 min and 16.3 ± 6.9 min, respectively. There were no major complications such as stent thrombosis or embolization and there were no in-hospital deaths. Post procedure overshunting and prolonged ventilatory support was a prominent feature. The median ventilation days was 3 (1-11 days). One patient died after 1 month due to respiratory syncytial virus pneumonia at the referring hospital. At 6 months follow-up, four had patent stents and four had blocked or restrictive stent flow. One patient received re-stenting at 4 months for restrictive stent flow. In three patients where microcomputed tomography of explanted stent was available, resorption of iron was 15% at 6 months and >65% at 16 months. Ductal stenting with IBS Angel™ is feasible and safe in selected patients. Because of early luminal loss, its use may be recommended for lesions with dual-source PBF with noncomplex PDA morphology that requires a short duration of palliation.


Emotional conflict adaptation predicts intrusive memories.
Why do some individuals experience intrusive emotional memories following stressful or traumatic events whereas others do not? Attentional control may contribute to the development of such memories by shielding attention to ongoing tasks from affective reactions to task-irrelevant emotional stimuli. The present study investigated whether individual differences in theability to exert cognitive control are associated with experiencing intrusive emotional memories after laboratory trauma. Sixty-one healthy women provided self-reported and experimentally derived measures of attentional control. They then viewed a trauma film in the laboratory and recorded intrusive memories for one week using a diary. Gaze avoidance during trauma film exposure was associated with more intrusive memories. Greater attentional control over emotion prior to film viewing, as assessed with the experimental task, predicted fewer intrusive memories while self-reported attentional control was unrelated to intrusive memories. Preexisting capacity to shield information processing from distraction may protect individuals from developing intrusive emotional memories following exposure to stress or trauma. These findings provide important clues for prevention and intervention science.


Integrative Approaches in the Treatment of Patients Affected by Lymphoma.
Lymphoma is the most frequent hematological malignancy with wide disease spectrum of watchful waiting period, active treatment, survivorship, and palliative care. All these steps impose unmet needs in terms of prevention, symptom alleviation, or prognosis. Complementary and integrative medicine (CIM) is widely used by patients with lymphoma to cope with such issues. Here, we describe the different CIM modalities that may be effective and safe for the management of patients with lymphoma. Low inflammatory diet and ginseng seem effective for lymphoma prevention. Pain and neuropathy may be improved using acupuncture, touch therapy and specific dietary supplements. Nausea/vomiting, fatigue, and insomnia may be relieved by acupuncture, mind-body, touch therapy, and certain dietary supplements. Vitamin D, curcumin, and some traditional medicine herbs may positively impact lymphoma prognosis. Finally, safety issues should be considered especially for the concomitant use of dietary supplements and lymphoma-directed therapies. CIM may be beneficial along the continuum of lymphoma management although safety concerns should be considered when used concomitantly with conventional therapy.


Early Nutrition as a Major Determinant of 'Immune Health': Implications for Allergy, Obesity and Other Noncommunicable Diseases.
Early-life nutritional exposures are significant determinants of the development and future health of all organ systems. The dramatic rise in infant immune diseases, most notably allergy, indicates the specific vulnerability of the immune system to early environmental changes. Dietary changes are at the center of the emerging epigenetic paradigms that underpin the rise in many modern inflammatory and metabolic diseases. There is growing evidence that exposures in pregnancy and the early postnatal period can modify gene expression and disease susceptibility. Although modern dietary changes are complex and involve changing patterns of many nutrients, there is also interest in the developmental effects of specific nutrients. Oligosaccharides (soluble fiber), antioxidants, polyunsaturated fatty acids, folate and other vitamins have documented effects on immune function as well as metabolism. Some have also been implicated in modified risk of allergic diseases in observational studies. Intervention studies are largely limited to trials with polyunsaturated fatty acids and oligosaccharides, showing preliminary but yet unconfirmed benefits in allergy prevention. Understanding how environmental influences disrupt the finely balanced development of immune and metabolic programming is of critical importance. Diet-sensitive pathways are likely to be crucial in these processes. While an epigenetic mechanism provides a strong explanation of how nutritional exposures can affect fetal gene expression and subsequent disease risk, other diet-induced tissue compositional changes may also contribute directly to altered immune and metabolic function--including diet-induced changes in the microbiome. A better understanding of nutritional programming of immune health, nutritional epigenetics and the biological processes sensitive to nutritional exposures early in life may lead to dietary strategies that provide more tolerogenic conditions during early immune programming and reduce the burden of many inflammatory diseases--not just allergy.


Carnosol, radiation and melanoma: a translational possibility.
To compare the genoprotective and radioprotective effect of carnosol (COL) against damage induced by ionizing radiation with similar effects produced by different antioxidant compounds. The genoprotective effect was studied by means of the micronucleus test for antimutagenic activity in which the reduction in the frequency of micronuclei was evaluated in cytokinesis-blocked cells of human lymphocytes. The radioprotective effects were studied by cell viability test (MTT) in PNT2 (normal prostate) and B16F10 (melanoma) cell lines when they were administered before exposure to different X-ray doses (4, 6, 8, 10 and 0 Gy). Carnosol shows a significant genoprotective capacity (p < 0.001) against radiation with a protection factor of 50 %, and a dose-reduction factor of 4.3. Cell survival obtained with COL administered before exposure to 10 Gy of X-rays showed a protection factor of 55.1 %, eliminating 39 % of radiation-induced cell death in normal epithelial cells of prostate (PNT2) (p < 0.001). However, in the melanoma cell lines (B16F10) assayed, COL acted not as a radioprotector, but as a sensitizing agent increasing the cellular death by 34 % (p < 0.01) and producing an enhancement ratio of 2.12. Carnosol may be developed as a radioprotective agent in the non-tumoral cells. However, in the B10F16 melanoma cells, melanogenesis is activated by COL leading to redistribution of the enzymatic balances of glutathione and cysteine-lyase production, which could compromise the intracellular redox defence system. This effect appears as an increase in the capacity of ionizing radiation-induced damage, and thus exhibits a paradoxical protective effect of COL on melanoma cells.


Different impact of two mutations of a novel compound heterozygous protein C deficiency with late onset thrombosis.
We investigated the alteration of coagulation state in a protein C (PC) deficiency pedigree and the impact of the PC gene mutations. The pedigree of a proband with cerebral hemorrhagic infarction had sixteen members with four generations. The plasma levels of PC activity (PC:A), protein S activity (PS:A), factor V:C and factor VIII:C, and routine coagulation tests were measured. Nine exons of the PC gene (PROC) were sequenced. Plasma PC:A and PC antigen (PC:Ag) of the proband were 26 and 18%, respectively, which was significantly lower than normal ranges. Two heterozygous missense mutations of PC in the proband were identified, T>G at site 6128 (exon 7) and G>C at site 8478 (exon 9) resulting in F139V and D255H, respectively. The family members with F139V (N = 4) or D255H (N = 4) had lower levels of PC:A and PC:Ag than members with wild-type PROC (N = 6). D255H mutation caused a more significant decrease in the levels of PC:A, PC:Ag and factor V:C as compared to F139V mutation (P < 0.05). Two independent mutations, F139V and D255H, of PROC reduce PC function. Compound heterozygous condition of the two mutations can cause synergistic PC deficiency, but resulting in later onset of cerebral thrombosis.


Topical treatment of melasma.
Melasma is a common hypermelanotic disorder affecting the face that is associated with considerable psychological impacts. The management of melasma is challenging and requires a long-term treatment plan. In addition to avoidance of aggravating factors like oral pills and ultraviolet exposure, topical therapy has remained the mainstay of treatment. Multiple options for topical treatment are available, of which hydroquinone (HQ) is the most commonly prescribed agent. Besides HQ, other topical agents for which varying degrees of evidence for clinical efficacy exist include azelaic acid, kojic acid, retinoids, topical steroids, glycolic acid, mequinol, and arbutin. Topical medications modify various stages of melanogenesis, the most common mode of action being inhibition of the enzyme, tyrosinase. Combination therapy is the preferred mode of treatment for the synergism and reduction of untoward effects. The most popular combination consists of HQ, a topical steroid, and retinoic acid. Prolonged HQ usage may lead to untoward effects like depigmentation and exogenous ochronosis. The search for safer alternatives has given rise to the development of many newer agents, several of them from natural sources. Well-designed controlled clinical trials are needed to clarify their role in the routine management of melasma.


Panayiotopoulos syndrome and symptomatic occipital lobe epilepsy of childhood: a clinical and EEG study.
Panayiotopoulos syndrome (PS) is an age-related seizure susceptibility syndrome that affects the central autonomic system. Although the majority of the few ictal recordings obtained so far suggest an occipital origin, semiological and interictal EEG data appear to favour more extensive involvement. In this study, the characteristics (including those based on semiology and EEG) of children with Panayiotopoulos syndrome (n=24) and those with lesion-related, symptomatic occipital lobe epilepsy (SOLE) (n=23) were compared. Detailed semiological information and EEG parameters including the localisation, distribution, density (n/sec), reactivity, and morphological characteristics of spike-wave foci and their relationship with different states of vigilance were compared between the two groups. The age at seizure onset was significantly younger in patients with symptomatic occipital lobe epilepsy than in those with PS (mean age at onset: 3.4 versus 5.6 years, respectively; p=0.044). Autonomic seizures (p=0.001) and ictal syncope (p=0.055) were more frequent in PS than in symptomatic occipital lobe epilepsy (87.5% and 37.5% versus 43.5% and 13%, respectively). The interictal spike-wave activity increased significantly during non-rapid eye movement (non-REM) sleep in both groups. The spike waves in non-REM seen in PS tended to spread mainly to central and centro-temporal regions. The results indicate that although common features do exist, Panayiotopoulos syndrome differs from symptomatic occipital lobe epilepsy and has a unique low epileptogenic threshold related to particular brain circuits.


Host range transforming gene of polyoma virus plays a role in virus assembly.
Polyoma virus host range transforming (hr-t) mutants are blocked in virion assembly. In normal 3T3 cells, a nonpermissive host, these mutants synthesize 30-40% as much viral DNA and 80-100% as much capsid proteins as does wild-type virus and yet produce only 1-2% as much infectious virus. Intermediates in virion assembly have been followed by [3H]thymidine incorporation. hr-t mutants synthesize 95S replicating minichromosomes, which accumulate as 75S forms. However, the latter fail to undergo efficient transition to 240S virion structures. This block in encapsidation is overcome in permissive hosts such as primary baby mouse kidney (BMK) epithelial cells. The block in assembly of 240S particles is accompanied by a failure to induce a series of acidic isoelectric forms of the major capsid protein, VP1. Multiple species of post-translationally modified VP1 are seen by two-dimensional gel electrophoresis in wild-type virus-infected cells. These acidic VP1 subspecies are decreased 6- to 10-fold in hr-t mutant-infected 3T3 cells but are produced in normal amounts when the same mutants infect BMK cells. When 3T3 cells are coinfected with hr-t mutant and wild-type viruses, normal amounts of the VP1 subspecies are present, and hr-t mutant viral DNA is efficiently packaged into virions. These studies demonstrate an important role of the hr-t gene of polyoma virus in virus assembly. Specifically, we propose that VP1 is a target for hr-t gene-controlled modification and that modified forms of VP1 are essential for encapsidation of viral minichromosomes.


Electroencephalographic similarities between chronic alcoholics and chronic, nonparanoid schizophrenics.
We compared the EEG power spectral density patterns for chronic, nonparanoid schizophrenics and age-matched chronic alcoholic and control subjects. Bilateral precentral (F-T) and postcentral (C-O) derivations were used in the analysis. The nonparanoid schizophrenics and alcoholics showed increased low-frequency activity (0 to 6 Hz) in all derivations in comparison to the control subjects. Chronic alcoholics were found to have increased high-frequency activity primarily in the precentral derivations. Nonparanoid schizophrenics showed increased power in the high-frequency bands predominantly in the left precentral derivation. We discuss the implications of patterns of differences concerning the issue of nonspecificity of the EEG in psychiatry.


Inflammatory bowel disease.
The causes of inflammatory bowel disease (IBD) continue to be an enigma. The incidence has stabilized in Western countries. Involvement of the upper gastrointestinal tract has been found in a high percentage of patients, and can be used to guide the work-up in patients with abdominal complaints. Ileoscopy must be added to the routine investigation when a suspicion of IBD exists. A number of new methods have been proposed, in particular Doppler sonography and magnifying chromoscopy, but their clinical contribution remains to be determined. Carcinoma surveillance is still the major diagnostic problem. New methods are available but need to be evaluated, particularly in patients at increased risk, such as those with primary sclerosing cholangitis.


Retinoic acid isomers applied to human skin in vivo each induce a 4-hydroxylase that inactivates only trans retinoic acid.
Application of all-trans retinoic acid to human skin for 4 d under occlusion produces a marked increase in retinoic acid 4-hydroxylase activity. In this study, the possible induction of other hydroxylase in response to 9-cis and 13-cis retinoic acid application to adult human skin in vivo was determined. Application of 0.1% all-trans, 0.1% 9-cis, and 0.1% 13-cis retinoic acid to human skin for 2 d resulted in induction of only all-trans retinoic acid 4-hydroxylase activity. The 4-hydroxylase activity in microsomes from the treated tissue ranged from 838 +/- 46 to 531 +/- 59 pg of 4- hydroxy all-trans retinoic acid formed/min/mg protein (n=6). These same preparations were unable to use 9-cis or 13-cis retinoic acid as substrate for the hydroxylation reaction. Extraction of the retinoic acid isomers from epidermis 48 h after application of 0.1% solution of each isomer yielded significant amounts of all-trans retinoic acid (36-72%) regardless of the isomer applied. The all-trans isomer produced by isomerization of both 9-cis and 13-cis retinoic acids is the likely inducer of the 4-hydroxylase. All-trans retinol and all-trans retinal were unable to compete with all-trans retinoic acid as substrate for 4-hydroxylase enzyme. The 4-hydroxylase induced in response to pharmacological doses of retinoic acids is specific for the all-trans isomer. The inability of 9-cis or 13-cis retinoic acid to induce their own hydroxylation and inactivation or act as substrate for the 4-hydroxylase in skin may have considerable implications in light of the clinical use of retinoids in the treatment of various diseases including cancers.


Does mosquito control have an effect on mosquito-borne disease? The case of Ross River virus disease and mosquito management in Queensland, Australia.
We examined the relationship between types of mosquito control programs and the mosquito-borne Ross River virus (RRV) disease in Queensland, Australia. Mosquito control information was collected through a survey of the responsible agencies (local governments), and RRV disease notification data were provided by the Queensland state health authority. The study developed a typology of mosquito control programs, based on the approaches used. Based on the analysis of data on RRV disease rates between mosquito control types within 4 climatic regions, each region had different combinations of mosquito control strategies in their programs; there were also general similarities in the relationship between program types and RRV rates between the regions. The long-term RRV disease rates were lower in areas where the mosquito control program included pre-emptive (rather than reactive) surveillance based on an extensive (rather than incomplete) knowledge of mosquito habitats, and where treatment of both saltwater and freshwater habitats (compared to only saltwater habitats, in coastal areas) occurred. The data indicate that mosquito control is an effective public health intervention to reduce mosquito-borne disease; hence, climate change adaptation strategies should ensure that adequate resources are available for effective vector control so as to manage the risk of mosquito-borne diseases.


Regulation of inositol 1,4,5-trisphosphate receptor function during mouse oocyte maturation.
At the time of fertilization, an increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)) underlies egg activation and initiation of development in all species studied to date. The inositol 1,4,5-trisphosphate receptor (IP(3)R1), which is mostly located in the endoplasmic reticulum (ER) mediates the majority of this Ca(2+) release. The sensitivity of IP(3)R1, that is, its Ca(2+) releasing capability, is increased during oocyte maturation so that the optimum [Ca(2+)](i) response concurs with fertilization, which in mammals occurs at metaphase of second meiosis. Multiple IP(3)R1 modifications affect its sensitivity, including phosphorylation, sub-cellular localization, and ER Ca(2+) concentration ([Ca(2+)](ER)). Here, we evaluated using mouse oocytes how each of these factors affected IP(3)R1 sensitivity. The capacity for IP(3)-induced Ca(2+) release markedly increased at the germinal vesicle breakdown stage, although oocytes only acquire the ability to initiate fertilization-like oscillations at later stages of maturation. The increase in IP(3)R1 sensitivity was underpinned by an increase in [Ca(2+)](ER) and receptor phosphorylation(s) but not by changes in IP(3)R1 cellular distribution, as inhibition of the former factors reduced Ca(2+) release, whereas inhibition of the latter had no impact. Therefore, the results suggest that the regulation of [Ca(2+)](ER) and IP(3)R1 phosphorylation during maturation enhance IP(3)R1 sensitivity rendering oocytes competent to initiate oscillations at the expected time of fertilization. The temporal discrepancy between the initiation of changes in IP(3)R1 sensitivity and acquisition of mature oscillatory capacity suggest that other mechanisms that regulate Ca(2+) homeostasis also shape the pattern of oscillations in mammalian eggs.


Rice (Oryza) hemoglobins.
Hemoglobins (Hbs) corresponding to non-symbiotic (nsHb) and truncated (tHb) Hbs have been identified in rice ( Oryza). This review discusses the major findings from the current studies on rice Hbs. At the molecular level, a family of the nshb genes, consisting of hb1, hb2, hb3, hb4 and hb5, and a single copy of the thb gene exist in Oryza sativa var. indica and O. sativa var. japonica, Hb transcripts coexist in rice organs and Hb polypeptides exist in rice embryonic and vegetative organs and in the cytoplasm of differentiating cells. At the structural level, the crystal structure of rice Hb1 has been elucidated, and the structures of the other rice Hbs have been modeled. Kinetic analysis indicated that rice Hb1 and 2, and possibly rice Hb3 and 4, exhibit an extremely high affinity for O 2, whereas rice Hb5 and tHb possibly exhibit a low to moderate affinity for O 2. Based on the accumulated information on the properties of rice Hbs and data from the analysis of other plant and non-plant Hbs, it is likely that Hbs play a variety of roles in rice organs, including O 2-transport, O 2-sensing, NO-scavenging and redox-signaling. From an evolutionary perspective, an outline for the evolution of rice Hbs is available. Rice nshb and thb genes vertically evolved through different lineages, rice nsHbs evolved into clade I and clade II lineages and rice nshbs and thbs evolved under the effect of neutral selection. This review also reveals lacunae in our ability to completely understand rice Hbs. Primary lacunae are the absence of experimental information about the precise functions of rice Hbs, the properties of modeled rice Hbs and the cis-elements and trans-acting factors that regulate the expression of rice hb genes, and the partial understanding of the evolution of rice Hbs.


MOLECULAR DETECTION OF ANTIBIOTIC-RESISTANCE DETERMINANTS IN ESCHERICHIA COLI ISOLATED FROM THE ENDANGERED AUSTRALIAN SEA LION (NEOPHOCA CINEREA).
Greater interaction between humans and wildlife populations poses significant risks of anthropogenic impact to natural ecosystems, especially in the marine environment. Understanding the spread of microorganisms at the marine interface is therefore important if we are to mitigate adverse effects on marine wildlife. We investigated the establishment of Escherichia coli in the endangered Australian sea lion (Neophoca cinerea) by comparing fecal isolation from wild and captive sea lion populations. Fecal samples were collected from wild colonies March 2009-September 2010 and from captive individuals March 2011-May 2013. Using molecular screening, we assigned a phylotype to E. coli isolates and determined the presence of integrons, mobile genetic elements that capture gene cassettes conferring resistance to antimicrobial agents common in fecal coliforms. Group B2 was the most abundant phylotype in all E. coli isolates (n = 37), with groups A, B1, and D also identified. Integrons were not observed in E. coli (n = 21) isolated from wild sea lions, but were identified in E. coli from captive animals (n = 16), from which class I integrases were detected in eight isolates. Sequencing of gene cassette arrays identified genes conferring resistance to streptomycin-spectinomycin (aadA1) and trimethoprim (dfrA17, dfrB4). Class II integrases were not detected in the E. coli isolates. The frequent detection in captive sea lions of E. coli with resistance genes commonly identified in human clinical cases suggests that conditions experienced in captivity may contribute to establishment. Identification of antibiotic resistance in the microbiota of Australian sea lions provides crucial information for disease management. Our data will inform conservation management strategies and provide a mechanism to monitor microorganism dissemination to sensitive pinniped populations.


Prognostic markers in feline hepatic lipidosis: a retrospective study of 71 cats.
Feline hepatic lipidosis (HL) is a common, potentially life-threatening disease resulting from prolonged anorexia and increased catabolism. This retrospective study included cats diagnosed with HL based on liver cytology or histopathology (years 2004-2015), and aimed to identify clinical and laboratory parameters associated with mortality. The study included 71 cats (47 females and 24 males) and 85 control cats with non-HL diseases. Most HL cats (90 per cent) were mixed breed, neutered (70; 99 per cent), female (47; 66 per cent), indoor cats (56; 79 per cent), fed dry commercial diets (44 cats; 62 per cent), and with a median age of 7.5 years (range 1.5-16.0). Common primary conditions included gastrointestinal diseases, pancreatitis and cholangiohepatitis (31 cats; 44 per cent) and stressful events (14; 20 per cent). HL was idiopathic in 20 cats (28 per cent). The overall mortality was 38 per cent (27/71 cats). Older age, as well as dullness, weakness, ptyalism, hypoproteinaemia, hypoalbuminaemia, increased serum creatine kinase activity, hypocholesterolaemia and hepatic failure at presentation were significantly (P≤0.033) associated with mortality. The primary disease was unassociated with mortality. Worsening hypoalbuminaemia, hyperammonaemia, hyperbilirubinaemia, electrolyte disorders, and occurrence of cavitary effusions or hypotension during hospitalisation were significantly (P≤0.045) associated with mortality. A decrease of serum β-hydroxybutyrate during hospitalisation was significantly (P=0.01) associated with survival, likely reflecting improvement in the catabolic state. The identified risk factors may be therapeutic targets.


Risk factors for osteoporosis in female patients with systemic lupus erythematosus.
In the last years it has been recognized that patients with systemic lupus erythematosus (SLE) are at high risk of osteoporosis (OP) and fractures, both occurring through disease-specific (chronic arthritis, reduced physical activity, induction of cytokines promoting bone resorption, renal impairment, endocrine factors) and nondisease-specific mechanisms (sunshine avoidance with consequent vitamin D deficiency, glucocorticoids, immunosuppressants and chronic anticoagulants). Regarding anticoagulants, subcutaneous heparin is crucial against the risk of recurrent thromboembolism or pregnancy loss, specifically in patients with SLE and anti-phospholipid syndrome (APS). Thus heparin-induced OP represents one of the hazards of this treatment, first because heparin must be used long-term and secondly because pregnancy and lactation themselves may predispose to OP and fractures. Current data suggest the use of prophylaxis with calcium and vitamin D in all patients treated with heparin during pregnancy. Nevertheless glucocorticoid-induced OP (GIOP) is considered the most serious risk factor for OP and fractures in SLE patients. All guidelines recommend general measures and supplementation with calcium and vitamin D in all patients. However when considering premenopausal patients, there is no generally recommended treatment. Bisphosphonates, which are considered the first choice therapy for the prevention and treatment of GIOP, should be used 'cautiously' in these patients. Therefore the potential risks and lack of efficacy data on fracture risk reduction in premenopausal patients must be weighed against their proven efficacy in postmenopausal patients.


Determination of berberine content in the stem extracts of Coscinium fenestratum by TLC densitometry.
To develop the optimal extraction procedure (i.e. maceration, percolation or Soxhlet extraction) and thin- layer chromatographic (TLC)-densitometric method for the determination of berberine content of Coscinium fenestratum. Maceration, percolation and Soxhlet extraction techniques were used to extract alkaloids from dried stems of C. fenestratum. The solvents used were 50 and 80% ethanol. Crude extracts and berberine content recovered from the TLC fingerprint were evaluated for chemical components of each extraction method. Precoated silica gel GF(254) plates were used as stationary phase while butanol:glacial acetic acid:water (14:3:4) was used as a mobile phase. Detection and quantitation of berberine were performed by densitometry at the wavelength of 415 nm over the linearity range of 240-840 ng (r(2) = 0.9982). The relative standard deviations from intraday and interday precisions were less than 4.13%. The recovery of standard berberine was 97.58-98.71% (%RSD = 3.85), and the limit of detection and quantitation were 25 and 50 ng/spot, respectively. Eighty percent ethanol gave a higher content of berberine than 50% ethanol. Berberine contents from maceration, percolation and Soxhlet extraction with 80% ethanol were 3.37+/- 0.30, 3.08+/- 0.38 and 2.67+/- 0.27% w/w, respectively. The TLC-densitometric method was simple, accurate and precise for quantitating berberine in the stem extract of C. fenestratum. Maceration with 80% ethanol gave the highest content of berberine in the extract. TLC of the extracts from different methods showed a similar pattern.


Isolation of Helicobacter pylori from saliva.
Helicobacter pylori was grown in low numbers from the saliva of one of nine patients who were positive for gastric H. pylori. The saliva-derived isolate from this patient was identical to the antral biopsy-derived isolate from the same patient and differed from isolates cultured from the antral biopsies of all other patients by soluble-protein electrophoresis, restriction endonuclease DNA analysis, and Southern blot hybridization. This is the first observation, to our knowledge, of the recovery of viable H. pylori from saliva.


Coordination of fingertip forces during human manipulation can emerge from independent neural networks controlling each engaged digit.
We investigated the coordination of fingertip forces in subjects who lifted an object (i) using the index finger and thumb of their right hand, (ii) using their left and right index fingers, and (iii) cooperatively with another subject using the right index finger. The forces applied normal and tangential to the two parallel grip surfaces of the test object and the vertical movement of the object were recorded. The friction between the object and the digits was varied independently at each surface between blocks of trials by changing the materials covering the grip surfaces. The object's weight and surface materials were held constant across consecutive trials. The performance was remarkably similar whether the task was shared by two subjects or carried out unimanually or bimanually by a single subject. The local friction was the main factor determining the normal:tangential force ratio employed at each digit-object interface. Irrespective of grasp configuration, the subjects adapted the force ratios to the local frictional conditions such that they maintained adequate safety margins against slips at each of the engaged digits during the various phases of the lifting task. Importantly, the observed force adjustments were not obligatory mechanical consequences of the task. In all three grasp configurations an incidental slip at one of the digits elicited a normal force increase at both engaged digits such that the normal:tangential force ratio was restored at the non-slipping digit and increased at the slipping digit. The initial development of the fingertip forces prior to object lift-off revealed that the subjects employed digit-specific anticipatory mechanisms using weight and frictional experiences in the previous trial. Because grasp stability was accomplished in a similar manner whether the task was carried out by one subject or cooperatively by two subjects, it was concluded that anticipatory adjustments of the fingertip forces can emerge from the action of anatomically independent neural networks controlling each engaged digit. In contrast, important aspects of the temporal coordination of the digits was organized by a "higher level" sensory-based control that influenced both digits. In lifts by single subjects this control was mast probably based on tactile and visual input and on communication between neural control mechanisms associated with each digit. In the two-subject grasp configuration this synchronization information was based on auditory and visual cues.


Ruthenium(II) Complex Incorporated UiO-67 Metal-Organic Framework Nanoparticles for Enhanced Two-Photon Fluorescence Imaging and Photodynamic Cancer Therapy.
Ruthenium(II) tris(bipyridyl) cationic complex (Ru(bpy)32+) incorporated UiO-67 (Universitetet i Oslo) nanoscale metal-organic frameworks (NMOFs) with an average diameter of ∼92 nm were developed as theranostic nanoplatform for in vitro two-photon fluorescence imaging and photodynamic therapy. After incorporation into porous UiO-67 nanoparticles, the quantum yield, luminescence lifetime, and two-photon fluorescence intensity of Ru(bpy)32+ guest molecules were much improved owing to the steric confinement effect of MOF pores. Benefiting from these merits, the as-synthesized nanoparticles managed to be internalized by A549 cells while providing excellent red fluorescence in cytoplasm upon excitation with 880 nm irradiation. Photodynamic therapeutic application of the Ru(bpy)32+-incorporated UiO-67 NMOFs was investigated in vitro. The Ru(bpy)32+-incorporated UiO-67 NMOFs exhibited good biocompatibility without irradiation while having good cell-killing rates upon irradiation. In view of these facts, the developed Ru(bpy)32+-incorporated NMOFs give a new potential pathway to achieve enhanced two-photon fluorescence imaging and photodynamic therapy.


Pasteurella multocida urinary tract infection.
Most Pasteurella multocida infections in humans have been associated with animal bites or scratches. While a variety of infections involving P multocida, unassociated with animal trauma, have been described, infections of the urinary tract are rare. We studied a case in which P multocida was isolated from the urine of a woman with advanced uterine cervical cancer. In most of the cases in which P multocida has been isolated from urine, the patients have had anatomic defects of the urinary tract, as well as an underlying chronic illness. These host-related characteristics appear to be important in the pathogenesis of P multocida urinary tract infection.


Constitutively Higher Level of GSTT2 in Esophageal Tissues From African Americans Protects Cells Against DNA Damage.
African American and European American individuals have a similar prevalence of gastroesophageal reflux disease (GERD), yet esophageal adenocarcinoma (EAC) disproportionately affects European American individuals. We investigated whether the esophageal squamous mucosa of African American individuals has features that protect against GERD-induced damage, compared with European American individuals. We performed transcriptional profile analysis of esophageal squamous mucosa tissues from 20 African American and 20 European American individuals (24 with no disease and 16 with Barrett's esophagus and/or EAC). We confirmed our findings in a cohort of 56 patients and analyzed DNA samples from patients to identify associated variants. Observations were validated using matched genomic sequence and expression data from lymphoblasts from the 1000 Genomes Project. A panel of esophageal samples from African American and European American subjects was used to confirm allele-related differences in protein levels. The esophageal squamous-derived cell line Het-1A and a rat esophagogastroduodenal anastomosis model for reflux-generated esophageal damage were used to investigate the effects of the DNA-damaging agent cumene-hydroperoxide (cum-OOH) and a chemopreventive cranberry proanthocyanidin (C-PAC) extract, respectively, on levels of protein and messenger RNA (mRNA). We found significantly higher levels of glutathione S-transferase theta 2 (GSTT2) mRNA in squamous mucosa from African American compared with European American individuals and associated these with variants within the GSTT2 locus in African American individuals. We confirmed that 2 previously identified genomic variants at the GSTT2 locus, a 37-kb deletion and a 17-bp promoter duplication, reduce expression of GSTT2 in tissues from European American individuals. The nonduplicated 17-bp promoter was more common in tissue samples from populations of African descendant. GSTT2 protected Het-1A esophageal squamous cells from cum-OOH-induced DNA damage. Addition of C-PAC increased GSTT2 expression in Het-1A cells incubated with cum-OOH and in rats with reflux-induced esophageal damage. C-PAC also reduced levels of DNA damage in reflux-exposed rat esophagi, as observed by reduced levels of phospho-H2A histone family member X. We found GSTT2 to protect esophageal squamous cells against DNA damage from genotoxic stress and that GSTT2 expression can be induced by C-PAC. Increased levels of GSTT2 in esophageal tissues of African American individuals might protect them from GERD-induced damage and contribute to the low incidence of EAC in this population.


Supplementary eye field during visual search: salience, cognitive control, and performance monitoring.
How supplementary eye field (SEF) contributes to visual search is unknown. Inputs from cortical and subcortical structures known to represent visual salience suggest that SEF may serve as an additional node in this network. This hypothesis was tested by recording action potentials and local field potentials (LFPs) in two monkeys performing an efficient pop-out visual search task. Target selection modulation, tuning width, and response magnitude of spikes and LFP in SEF were compared with those in frontal eye field. Surprisingly, only ∼2% of SEF neurons and ∼8% of SEF LFP sites selected the location of the search target. The absence of salience in SEF may be due to an absence of appropriate visual afferents, which suggests that these inputs are a necessary anatomical feature of areas representing salience. We also tested whether SEF contributes to overcoming the automatic tendency to respond to a primed color when the target identity switches during priming of pop-out. Very few SEF neurons or LFP sites modulated in association with performance deficits following target switches. However, a subset of SEF neurons and LFPs exhibited strong modulation following erroneous saccades to a distractor. Altogether, these results suggest that SEF plays a limited role in controlling ongoing visual search behavior, but may play a larger role in monitoring search performance.


Fire Usage and Ancient Hominin Detoxification Genes: Protective Ancestral Variants Dominate While Additional Derived Risk Variants Appear in Modern Humans.
Studies of the defence capacity of ancient hominins against toxic substances may contribute importantly to the reconstruction of their niche, including their diets and use of fire. Fire usage implies frequent exposure to hazardous compounds from smoke and heated food, known to affect general health and fertility, probably resulting in genetic selection for improved detoxification. To investigate whether such genetic selection occurred, we investigated the alleles in Neanderthals, Denisovans and modern humans at gene polymorphisms well-known to be relevant from modern human epidemiological studies of habitual tobacco smoke exposure and mechanistic evidence. We compared these with the alleles in chimpanzees and gorillas. Neanderthal and Denisovan hominins predominantly possess gene variants conferring increased resistance to these toxic compounds. Surprisingly, we observed the same in chimpanzees and gorillas, implying that less efficient variants are derived and mainly evolved in modern humans. Less efficient variants are observable from the first early Upper Palaeolithic hunter-gatherers onwards. While not clarifying the deep history of fire use, our results highlight the long-term stability of the genes under consideration despite major changes in the hominin dietary niche. Specifically for detoxification gene variants characterised as deleterious by epidemiological studies, our results confirm the predominantly recent appearance reported for deleterious human gene variants, suggesting substantial impact of recent human population history, including pre-Holocene expansions.


The 18O/16O and 17O/16O ratios in atmospheric nitrous oxide: A mass-independent anomaly
Measurements of the oxygen isotope ratios (18O/16O and 17O/16O) in atmospheric nitrous oxide (N2O) from La Jolla, Pasadena, and the White Mountain Research Station (elevation, 3801 meters) in California and the White Sands Missile Range in New Mexico show that N2O has a mass-independent composition. These data suggest the presence of a previously undefined atmospheric process. The La Jolla samples can be explained by a mixing between an atmospherically derived source of mass-independent N2O and biologically derived mass-dependent N2O. Possible origins of the mass-independent anomaly in N2O are discussed.


Biochemical and genetic evidence for the transfer of Mycobacterium tuberculosis subsp. caprae Aranaz et al. 1999 to the species Mycobacterium bovis Karlson and Lessel 1970 (approved lists 1980) as Mycobacterium bovis subsp. caprae comb. nov.
We propose to replace the species designation Mycobacterium tuberculosis subsp. caprae (Aranaz et al. 1999) by Mycobacterium bovis subsp. caprae comb. nov., since isolates of this subspecies share their main growth, biochemical and genetic characteristics with M. bovis and not with M. tuberculosis. These include negative biochemical test results for niacin accumulation and nitrate reduction as well as genetic features like the presence of an M. bovis-specific mutation in the oxyR locus, absence of the mtp40 sequence and a specific mutation in the gyrB gene, all of which have been described as characteristics for the differentiation of M. bovis. The only obvious biochemical character that differentiates the caprae subtype from other M. bovis isolates is susceptibility to pyrazinamide (PZA), which is due to the lack of a single point mutation in the pncA gene. However, susceptibility to PZA among clinical isolates of M. bovis isolates has been reported previously and, thus, may now been explained by a PZA-susceptible subspecies of M. bovis. We conclude that the species designation M. tuberculosis subsp. caprae is misleading and not correct in light of the biochemical and genetic characteristics and propose that the accurate designation of isolates of this subtype is M. bovis subsp. caprae.


Biological significance of metals partitioned to subcellular fractions within earthworms (Aporrectodea caliginosa).
Metal ions in excess of metabolic requirements are potentially toxic and must be removed from the vicinity of important biological molecules to protect organisms from adverse effects. Correspondingly, metals are sequestrated in various forms, defining the accumulation pattern and the magnitude of steady-state levels reached. To investigate the subcellular fractions over which Ca, Mg, Fe, Cu, Zn, Cd, Pb, Ni, and As are distributed, earthworms (Aporrectodea caliginosa) collected from the field were analyzed by isolating metal-rich granules and tissue fragments from intracellular microsomal and cytosolic fractions (i.e., heat-stable proteins and heat-denatured proteins). The fractions showed metal-specific binding capacity. Cadmium was mainly retrieved from the protein fractions. Copper was equally distributed over the protein fraction and the fraction comprising tissue fragments, cell membranes, and intact cells. Zinc, Ca, Mg, and As were mainly found in this fraction as well. Lead, Fe, and Ni were mainly isolated from the granular fraction. To study accumulation kinetics in the different fractions, three experiments were conducted in which earthworms were exposed to metal-spiked soil and a soil contaminated by anthropogenic inputs and, indigenous earthworms were exposed to field soils. Although kinetics showed variation, linear uptake and steady-state types of accumulation patterns could be understood according to subcellular compartmentalization. For risk assessment purposes, subcellular distribution of metals might allow for a more precise estimate of effects than total body burden. Identification of subcellular partitioning appears useful in determining the biological significance of steady-state levels reached in animals.


Integrating the physician into the organization decision-making process.
Physicians need to be involved in organizational decision making, and institutional goals are achieved through the integration of operational quality committees.


BMI and fracture risk in older men: the osteoporotic fractures in men study (MrOS).
Low body mass index (BMI) is a risk factor for fracture, but little is known about the association between high BMI and fracture risk. We evaluated the association between BMI and fracture in the Osteoporotic Fractures in Men Study (MrOS), a cohort of 5995 US men 65 years of age and older. Standardized measures included weight, height, and hip bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA); medical history; lifestyle; and physical performance. Only 6 men (0.1%) were underweight (<18.5 kg/m(2)); therefore, men in this category were excluded. Also, 27% of men had normal BMI (18.5 to 24.9 kg/m(2)), 52% were overweight (25 to 29.9 kg/m(2)), 18% were obese I (30 to 34.9 kg/m(2)), and 3% were obese II (35 to 39.9 kg/m(2)). Overall, nonspine fracture incidence was 16.1 per 1000 person-years, and hip fracture incidence was 3.1 per 1000 person-years. In age-, race-, and BMD-adjusted models, compared with normal weight, the hazard ratio (HR) for nonspine fracture was 1.04 [95% confidence interval (CI) 0.87-1.25] for overweight, 1.29 (95% CI 1.00-1.67) for obese I, and 1.94 (95% CI 1.25-3.02) for obese II. Associations were weaker and not statistically significant after adjustment for mobility limitations and walking pace (HR = 1.02, 95% CI 0.84-1.23, for overweight; HR = 1.12, 95% CI 0.86-1.46, for obese I, and HR = 1.44, 95% CI 0.90-2.28, for obese II). Obesity is common among older men, and when BMD is held constant, it is associated with an increased risk of fracture. This association is at least partially explained by worse physical function in obese men.


Effects of meteo-oceanographic conditions on the weathering processes of oil spills in northeastern Brazil.
This paper presents the graphical results of the Lagrangian-model and the weathering processes associated with oil spills in the tropical South Atlantic, taking into account the meteorological and oceanographic conditions of the study region. The scenarios were created in the Brazilian-NE waters adjacent, with simulation times of 670 h, and densities of 35, 25, and 15API with volume of 1590 m3 were considered. The main results showed that the meteo-oceanographic characteristics of the study region influence the trajectories and weathering processes in the oil spill. The trajectories varied for each launch point and reached the continent severely in January and October. The associated weathering processes showed higher rates in September and lower rates in April, indicative of the influence of phenomena such as Intertropical Tropical Convergence Zone and warm pool in the South Atlantic region. Sea surface temperature and wind speed are key factors that correlate positively with these months.


Effects of Tripterygium glycoside treatment on experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease mediated by CD4+ T cells. It is characterized by mononuclear cell infiltration around the small blood vessels in the central nervous system (CNS). Previous investigations have found that apoptosis is associated with the occurrence and development of autoimmune disease, and that mononuclear cell apoptosis and clearance from the CNS is one of the repair mechanisms of EAE. Tripterygium wilfordii glycoside (TWP) is an organic matter isolated from Tripterygium wilfordii, which has anti‑inflammatory and immunosuppressive effects. In the present study, male Lewis rats were randomly divided into a normal control, EAE and TWP groups. Rats in EAE and TWP groups received injections of emulsified EAE antigen (myelin protein) at two points on the footpad while control group received PBS. The TWP group was then treated with TWP daily for 21 days. Symptoms and nerve function scores were observed and evaluated. Specimens of blood, brain and spinal cord were collected for further pathological examination, Tunel assay, ELISA and immunohistochemistry were performed to examine the effect of TWP on the onset of EAE, and changes in CNS inflammatory infiltration, cell apoptosis, and the expression of nuclear factor (NF)‑κB P65 and interleukin (IL)‑2. The results showed that the TWP treatment group exhibited decreased EAE and delayed onset, compared with the control. The clinical symptoms were significantly reduced and alleviation of inflammatory cell infiltration was observed. Compared with the EAE group, a higher inflammatory cell apoptotic rate, and reduced serum levels of IL‑2 and NF‑κB p65‑positive cells were observed in the TWP treatment group. Therefore, TWP effectively inhibited EAE via the inhibition of CNS inflammatory cell infiltration, enhancement of inflammatory cell apoptosis, and downregulation of the expression of NF‑κB and IL‑2.


Potential of glucose-lowering drugs to reduce cardiovascular events.
Although a clear relationship exists between glycosylated hemoglobin and cardiovascular (CV) disease in individuals with type 2 diabetes mellitus (T2DM) in epidemiologic studies, data from prospective studies are less clear. Earlier prospective studies examining intensive glucose lowering suffered from a lack of statistical power to show CV event reduction, as well as a lack of durable glycemic control and relatively poor control of associated CV risk factors. Although recent CV outcome trials comparing intensive glycemic compared with standard glycemic control have been disappointing, CV event rates appear to be declining substantially in T2DM individuals in the setting of aggressive global CV risk factor modification. No single hypoglycemic agent or combination of agents was associated with increased CV events or mortality. A comprehensive strategy of multifactorial intervention including aggressive and durable glycemic blood pressure, and lipid lowering, aspirin usage, and lifestyle modifications is beneficial in reducing macrovascular and microvascular events in T2DM individuals.


Atopic dermatitis: serum immunoglobulins and T-lymphocyte subpopulations.
A group of patients with atopic dermatitis who attended the Allergy Outpatient Service of the Hermanos Ameijeiras Clinical Surgical Hospital from May, 1987 to May, 1988 were studied. The patients were assigned to 2 groups; the first one composed of 38 patients and the second one composed of 12 non-allergic, supposedly healthy subjects. Different tests were carried out for the quantification of total serum immunoglobulins (A, G, M, E) by means of the radial immunodiffusion method and the ELISA ultramicromethod. They were also submitted to quantification of lymphocyte subpopulations by means of the indirect immunofluorescence test with monoclonal antibodies, using Cuban antiserum prepared at the National Institute of Oncology and Radiobiology. In our study IgG and IgA values were within normal limits in patients, contrary to the statistically significant increase in IgM and IgE values. The relative values of total T-lymphocytes (anti-T3) and of the suppressor lymphocyte subpopulations decreased.


Incident cerebral microbleeds and hypertension defined by the 2017 ACC/AHA Guidelines.
The cut-off for hypertension was lowered to blood pressure (BP) over 130/80 mmHg in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline. Whether the new definition of hypertension remains a potent risk factor of cerebral microbleeds (CMBs) is uncertain. We aimed to analyze the relationship between the new definition of hypertension and incident CMBs in a 7-year longitudinal community study. This study is a sub-study of the Shanghai Aging Study (SAS). A total of 317 participants without stroke or dementia were included at baseline (2009-2011), and were invited to repeated clinical examinations and cerebral magnetic resonance imaging (MRI) at follow-up (2016-2018). CMBs at baseline and follow-up were evaluated on T2*-weighted gradient recalled echo (GRE) and susceptibility-weighted angiography (SWAN) sequence of MRI. We classified baseline BP into four categories: normal BP, elevated systolic BP, stage 1 hypertension and stage 2 hypertension according to the ACC/AHA guideline. We assessed the associations between BP categories and incident CMBs by generalized linear models. A total of 159 participants (median age, 67 years) completed follow-up examinations with a mean interval of 6.9 years. Both stage 1 and stage 2 hypertension at baseline were significantly related with a higher risk of incident CMBs (IRR 2.77, 95% CI, 1.11-6.91, P=0.028; IRR 3.04, 95% CI, 1.29-7.16, P=0.011, respectively), indicating dose-response effects across BP categories. Participants with ≥5 incident CMBs or incident CMBs in the deep locations all had baseline stage 1 and 2 hypertension. Participants with baseline stage 1 and stage 2 hypertension had a significantly higher risk of incident CMBs in this 7-year longitudinal community cohort.


Neonatal overfeeding induced by small litter rearing causes altered glucocorticoid metabolism in rats.
Elevated glucocorticoid (GC) activity may be involved in the development of the metabolic syndrome. Tissue GC exposure is determined by the tissue-specific GC-activating enzyme 11β-hydroxysteriod dehydrogenase type 1 (11β-HSD1) and the GC-inactivating enzyme 5α-reductase type 1 (5αR1), as well as 5β-reductase (5βR). Our aim was to study the effects of neonatal overfeeding induced by small litter rearing on the expression of GC-regulating enzymes in adipose tissue and/or liver and on obesity-related metabolic disturbances during development. Male Sprague-Dawley rat pup litters were adjusted to litter sizes of three (small litters, SL) or ten (normal litters, NL) on postnatal day 3 and then given standard chow from postnatal week 3 onward (W3). Small litter rearing induced obesity, hyperinsulinemia, and higher circulating corticosterone in adults. 11β-HSD1 expression and enzyme activity in retroperitoneal, but not in epididymal, adipose tissue increased with postnatal time and peaked at W5/W6 in both groups before declining. From W8, 11β-HSD1 expression and enzyme activity levels in retroperitoneal fat persisted at significantly higher levels in SL compared to NL rats. Hepatic 11β-HSD1 enzyme activity in SL rats was elevated from W3 to W16 compared to NL rats. Hepatic 5αR1 and 5βR expression was higher in SL compared to NL rats after weaning until W6, whereupon expression decreased in the SL rats and remained similar to that in NL rats. In conclusion, small litter rearing in rats induced peripheral tissue-specific alterations in 11β-HSD1 expression and activity and 5αR1 and 5βR expression during puberty, which could contribute to elevated tissue-specific GC exposure and aggravate the development of metabolic dysregulation in adults.


Determination of malachite green residues in fish using a highly sensitive electrochemiluminescence method combined with molecularly imprinted solid phase extraction.
An electrochemiluminescence (ECL) inhibition method combined with molecularly imprinted solid phase extraction (MISPE) was developed for quantitative determination of malachite green (MG) residues in fish. It was found that MG could strongly inhibit the ECL signal of luminol. Under the optimized conditions, the quenched ECL intensity versus the logarithm of the concentration of MG was in good linear relationship over a concentration range from 20 to 5000 ppt. The method detection limit was found to be about 6 ppt. Molecularly imprinted polymers (MIPs) were synthesized as solid phase extraction (SPE) sorbents, and MISPE was used for the selective extraction and purification of MG. By carrying out the oxidation reaction with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), which could convert leucomalachite green (LMG) into MG, this method was successfully applied to determine MG residues in fish. A possible mechanism for the quenching effects of MG on luminol was also proposed.


Antibacterial activity and mechanism of action of the silver ion in Staphylococcus aureus and Escherichia coli.
The antibacterial effect and mechanism of action of a silver ion solution that was electrically generated were investigated for Staphylococcus aureus and Escherichia coli by analyzing the growth, morphology, and ultrastructure of the bacterial cells following treatment with the silver ion solution. Bacteria were exposed to the silver ion solution for various lengths of time, and the antibacterial effect of the solution was tested using the conventional plate count method and flow cytometric (FC) analysis. Reductions of more than 5 log(10) CFU/ml of both S. aureus and E. coli bacteria were confirmed after 90 min of treatment with the silver ion solution. Significant reduction of S. aureus and E. coli cells was also observed by FC analysis; however, the reduction rate determined by FC analysis was less than that determined by the conventional plate count method. These differences may be attributed to the presence of bacteria in an active but nonculturable (ABNC) state after treatment with the silver ion solution. Transmission electron microscopy showed considerable changes in the bacterial cell membranes upon silver ion treatment, which might be the cause or consequence of cell death. In conclusion, the results of the present study suggest that silver ions may cause S. aureus and E. coli bacteria to reach an ABNC state and eventually die.


Hydration testing in collegiate wrestlers undergoing hypertonic dehydration.
Because dehydration (DEH) violates assumptions used in the assessment of body composition, hydration testing has become an integral part of minimal weight (MW) assessment. To determine the accuracy of hydration tests for the detection and quantification of hypertonic DEH. Twenty-five male collegiate wrestlers (mean +/- SD, age: 20.0 +/- 1.4 yr, height: 175.0 +/- 7.1 cm, body mass: 81.7 +/- 15.3 kg) had their hydration assessed under well-controlled conditions of euhydration (EUH) and DEH. The DEH phase occurred on the same day as EUH, after subjects acutely dehydrated 2-6% of body weight through fluid/food restriction and exercise in a hot environment. All hydration tests except plasma potassium significantly increased from EUH to DEH, and meaningful cutoff values could be established for most tests. Cutoff values for urine tests were 586 mOsm.L(-1) for osmolality and 71 mEq.L(-1) for potassium. Plasma cutoff values were 293 mOsm.L(-1) for osmolality, 140 mEq.L(-1) for sodium, 103 mEq.L(-1) for chloride, and 3.5 pg.mL(-1) for arginine vasopressin. For ratio tests, a urine:plasma osmolality of 2.06 and an extracellular:intracellular water of 0.533 measured by the bioelectrical impedance spectroscopy were cutoff values. For urine specific gravity, a cutoff value of 1.020 g.mL(-1) had a sensitivity and specificity of 96% each for the automated harmonic oscillation technique and 87% and 91% (respectively) for the dipstick technique. Protein (by dipstick) was detected in 5% of subjects in EUH, and 100% of subjects in DEH. Correlations between hydration tests and dehydration were only low to moderate. This study supports a specific gravity cutoff of 1.020 g.mL(-1) for the identification of hypertonic DEH. Future research should test the cutoff values established in this study and explore the relationship between DEH and urine protein.


A milk formula containing maltodextrin, vs. lactose, as main carbohydrate source, improves cognitive performance of piglets in a spatial task.
In recent years, lactose-free and low-lactose infant formulas have been increasingly used. The impact of using different carbohydrates than lactose on later cognition of formula-fed infants remains, however, unknown. We examined the effects of providing formulas containing either digestible maltodextrin or lactose as main carbohydrate source (28% of total nutrient composition) on cognitive performance of piglets. Piglets received the formulas from 1 to 9 weeks of age and, starting at 12 weeks, were individually tested in a spatial holeboard task (n = 8 pens/formula), in which they had to learn and memorize a configuration of baited buckets. After 28 acquisition trials, piglets were subjected to 16 reversal trials in which the location of the baited buckets was changed. Piglets fed the maltodextrin-based formula had higher reference memory (RM) scores than piglets fed the lactose-based formula towards the end of acquisition. During the switch of configuration, piglets offered the maltodextrin-based formula tended to have higher RM scores and make fewer RM errors than piglets offered the lactose-based formula. Working (short-term) memory was not affected by the formulas. Compared to lactose, the use of maltodextrin in milk formulas improved long-term spatial memory of piglets, even weeks after the end of the intervention.


Ageing, lifestyle modifications, and cardiovascular disease in developing countries.
Developing countries face the double menace of still prevalent infectious diseases and increasing cardiovascular disease (CVD) with epidemic proportions in the near future, linked to demographic changes (expansion and ageing), and to urbanisation and lifestyle modifications. It is estimated that the elderly population will increase globally (over 80% during the next 25 years), with a large share of this rise in the developing world because of expanding populations. Increasing longevity prolongs the time exposure to risk factors, resulting in a greater probability of CVD. As a paradox, increased longevity due to improved social and economical conditions associated with lifestyle changes in the direction of a rich diet and sedentary habits in the last century, is one of the main contributors to the incremental trend in CVD. The variable increase rate of CVD in different nations may reflect different stages of "epidemiological transition" and it is probable that the relatively slow changes seen in developing populations through the epidemiological transition may occur at an accelerated pace in individuals migrating from nations in need to affluent societies (i.e. Hispanics to the USA, Africans to Europe). Because of restrained economic conditions in the developing world, the greatest gains in controlling the CVD epidemic lies in its prevention. Healthy foods should be widely available and affordable, and healthy dietary practices such as increased consumption of fresh fruits and vegetables, reduced consumption of saturated fat, salt, and simple sugars, may be promoted in all populations. Specific strategies for smoking and overweight control may be regulation of marketed tobacco and unhealthy fast food and promotion of an active lifestyle. Greater longevity and economic progress are accompanied by an increasing burden of CVD and other chronic diseases with an important decrease in quality of life, which should question the benefit of these additional years without quality.


Syndecan-1 regulates the biological activities of interleukin-34.
IL-34 is a challenging cytokine sharing functional similarities with M-CSF through M-CSFR activation. It also plays a singular role that has recently been explained in the brain, through a binding to the receptor protein tyrosine phosphatase RPTPβ/ζ. The aim of this paper was to look for alternative binding of IL-34 on other cell types. Myeloid cells (HL-60, U-937, THP-1) were used as cells intrinsically expressing M-CSFR, and M-CSFR was expressed in TF-1 and HEK293 cells. IL-34 binding was studied by Scatchard and binding inhibition assays, using 125I-radiolabelled cytokines, and surface plasmon resonance. M-CSFR activation was analysed by Western blot after glycosaminoglycans abrasion, syndecan-1 overexpression or repression and addition of a blocking anti-syndecan antibody. M-CSF and IL-34 induced different patterns of M-CSFR phosphorylations, suggesting the existence of alternative binding for IL-34. Binding experiments and chondroitinase treatment confirmed low affinity binding to chondroitin sulphate chains on cells lacking both M-CSFR and RPTPβ/ζ. Amongst the proteoglycans with chondroitin sulphate chains, syndecan-1 was able to modulate the IL-34-induced M-CSFR signalling pathways. Interestingly, IL-34 induced the migration of syndecan-1 expressing cells. Indeed, IL-34 significantly increased the migration of THP-1 and M2a macrophages that was inhibited by addition of a blocking anti-syndecan-1 antibody. This paper provides evidence of alternative binding of IL-34 to chondroitin sulphates and syndecan-1 at the cell surface that modulates M-CSFR activation. In addition, IL-34-induced myeloid cell migration is a syndecan-1 dependent mechanism.