An overview of chronic disease models: a systematic literature review.
The objective of our study was to examine various existing chronic disease models, their elements and their role in the management of Diabetes, Chronic Obstructive Pulmonary Disease (COPD), and Cardiovascular diseases (CVD). A literature search was performed using PubMed and CINHAL during a period of January 2003- March 2011. Following key terms were used either in single or in combination such as "Chronic Disease Model" AND "Diabetes Mellitus" OR "COPD" OR "CVD". A total of 23 studies were included in the final analysis. Majority of the studies were US-based. Five chronic disease models included Chronic Care Model (CCM), Improving Chronic Illness Care (ICIC), and Innovative Care for Chronic Conditions (ICCC), Stanford Model (SM) and Community based Transition Model (CBTM). CCM was the most studied model. Elements studied included delivery system design and self-management support (87%), clinical information system and decision support (57%) and health system organization (52%). Elements including center care on the patient and family (13%), patient safety (4%), community policies (4%), built integrated health care (4%) and remote patient monitoring (4%) have not been well studied. Other elements including support paradigm shift, manage political environment, align sectoral policies for health, use healthcare personnel more effectively, support patients in their communities, emphasize prevention, identify patient specific concerns related to the transition process, and health literacy between visits and treatments have also not been well studied in the existing literature. It was unclear to what extent the results generated is applicable to different populations and locations and therefore is an area of future research. Future studies are also needed to test chronic disease models in settings where more racially and ethnically representative patients receive chronic care. Future program development should also include information on other barriers including transportation issues, finances and lack of services.


Pulmonary arteriovenous malformation in children.
Although pulmonary arteriovenous malformations (PAVM) are relatively rare in children, they are important in the differential diagnosis of common pulmonary problems, such as hypoxemia, hemoptysis and dyspnea on exertion. We report the cases of two PAVM patients with different presentations and describe the treatment strategies.


Elevation of fibrinogen due to loss of ovarian function enhances actin ring formation and leads to increased bone resorption.
The aim of the present study was to evaluate the effect of fibrinogen on number and function of osteoclasts (OC) consequently resulting in bone loss. It was hypothesized that the enhanced level of released fibrinogen due to loss of ovarian function caused bone loss by acting on OCs. Bone loss was induced by ovariectomy (OVX) in mice and analyzed by micro-CT. The effect of fibrinogen on OCs was evaluated by tartrate-resistant acid phosphatase, annexin V, actin staining, pit formation observed on dentine slices, and Western blotting. Exogenous fibrinogen increased OC survival, actin ring formation, and bone resorption in vitro. The effect of fibrinogen was dependent on β(3)-integrin, which is a marker for mature OCs. Fibrinogen induced the activation of transforming oncogene from Ak strain (Akt), Ras-related C3 botulinum toxin substrate 1 (Rac1), and Rho family of GTPase (Rho) and the degradation of the Bcl-2 interacting mediator of cell death (Bim) in a manner similar to macrophage colony-stimulating factor (M-CSF). OVX increased plasma fibrinogen and serum M-CSF together with elevated actin ring formation and bone loss. The increased fibrinogen level due to loss of ovarian function may contribute, at least partly, to bone loss through the enhanced number and activity of OCs.


Ground reaction force and joint moment estimation during gait using an Azure Kinect-driven musculoskeletal modeling approach.
Gait analysis is burdened by time and equipment costs, interpretation, and accessibility of three-dimensional motion analysis systems. Evidence suggests growing adoption of gait testing in the shift toward evidence-based medicine. Further developments addressing these barriers will aid its efficacy in clinical practice. Previous research aiming to develop gait analysis systems for kinetics estimation using the Kinect V2 have provided promising results yet modified approaches using the latest hardware may further aid kinetics estimation accuracy RESEARCH QUESTION: Can a single Azure Kinect sensor combined with a musculoskeletal modeling approach provide kinetics estimations during gait similar to those obtained from marker-based systems with embedded force platforms? Ten subjects were recruited to perform three walking trials at their normal speed. Trials were recorded using an eight-camera optoelectronic system with two embedded force plates and a single Azure Kinect sensor. Marker and depth data were both used to drive a musculoskeletal model using the AnyBody Modeling System. Predicted kinetics from the Azure Kinect-driven model, including ground reaction force (GRF) and joint moments, were compared to measured values using root meansquared error (RMSE), normalized RMSE, Pearson correlation, concordance correlation, and statistical parametric mapping RESULTS: High to very high correlations were observed for anteroposterior GRF (ρ = 0.889), vertical GRF (ρ = 0.940), and sagittal hip (ρ = 0.805) and ankle (ρ = 0.876) moments. RMSEs were 1.2 ± 2.2 (%BW), 3.2 ± 5.7 (%BW), 0.7 ± 0.1.3 (%BWH), and 0.6 ± 1.0 (%BWH) SIGNIFICANCE: The proposed approach using the Azure Kinect provided higher accuracy compared to previous studies using the Kinect V2 potentially due to improved foot tracking by the Azure Kinect. Future studies should seek to optimize ground contact parameters and focus on regions of error between predicted and measured kinetics highlighted currently for further improvements in kinetic estimations.


[Antipsychotics in psychiatry.].
In this article we have tried to situate the anti-psychotic drugs within modern psychiatry in relation to the various therapies for schizophrenia. Without entering into detail, we have touched upon the main advantages and disadvantages of neuroleptics. We conclude that the advantages outweight the disadvantages. However, we have also stressed the necessity of selecting patients carefully and of taking certain precautions in regard to the neurological effects of anti-psychotic drugs currently available in clinics.


Attention-wise masked graph contrastive learning for predicting molecular property.
Accurate and efficient prediction of the molecular property is one of the fundamental problems in drug research and development. Recent advancements in representation learning have been shown to greatly improve the performance of molecular property prediction. However, due to limited labeled data, supervised learning-based molecular representation algorithms can only search limited chemical space and suffer from poor generalizability. In this work, we proposed a self-supervised learning method, ATMOL, for molecular representation learning and properties prediction. We developed a novel molecular graph augmentation strategy, referred to as attention-wise graph masking, to generate challenging positive samples for contrastive learning. We adopted the graph attention network as the molecular graph encoder, and leveraged the learned attention weights as masking guidance to generate molecular augmentation graphs. By minimization of the contrastive loss between original graph and augmented graph, our model can capture important molecular structure and higher order semantic information. Extensive experiments showed that our attention-wise graph mask contrastive learning exhibited state-of-the-art performance in a couple of downstream molecular property prediction tasks. We also verified that our model pretrained on larger scale of unlabeled data improved the generalization of learned molecular representation. Moreover, visualization of the attention heatmaps showed meaningful patterns indicative of atoms and atomic groups important to specific molecular property.


Beat-to-Beat Patterning of Sinus Rhythm Reveals Non-linear Rhythm in the Dog Compared to the Human.
The human and dog have sinus arrhythmia; however, the beat-to-beat interval changes were hypothesized to be different. Geometric analyses (R-R interval tachograms, dynamic Poincaré plots) to examine rate changes on a beat-to-beat basis were analyzed along with time and frequency domain heart rate variability from 40 human and 130 canine 24-h electrocardiographic recordings. Humans had bell-shaped beat-interval distributions, narrow interval bands across time with continuous interval change and linear changes in rate. In contrast, dogs had skewed non-singular beat distributions, wide interval bands {despite faster average heart rate of dogs [mean (range); 81 (64-119)] bpm compared to humans [74.5 (59-103) p = 0.005]} with regions displaying a paucity of intervals (zone of avoidance) and linear plus non-linear rate changes. In the dog, dynamic Poincaré plots showed linear rate changes as intervals prolonged until a point of divergence from the line of identity at a mean interval of 598.5 (95% CI: 583.5-613.5) ms (bifurcation interval). The dog had bimodal beat distribution during sleep with slower rates and greater variability than during active hours that showed singular interval distributions, higher rates and less variability. During sleep, Poincaré plots of the dog had clustered or branched patterns of intervals. A slower rate supported greater parasympathetic modulation with a branched compared to the clustered distribution. Treatment with atropine eliminated the non-linear patterns, while hydromorphone shifted the bifurcated branching and beat clustering to longer intervals. These results demonstrate the unique non-linear nature of beat-to-beat variability in the dog compared to humans with increases in interval duration (decrease heart rate). These results provoke the possibility that changes are linear with a dominant sympathetic modulation and non-linear with a dominant parasympathetic modulation. The abrupt bifurcation, zone of avoidance and beat-to-beat patterning are concordant with other studies demonstrating the development of exit block from the sinus node with parasympathetic modulation influencing not only the oscillation of the pacing cells, but conduction to the atria. Studies are required to associate the in vivo sinus node beat patterns identified in this study to the mapping of sinus impulse origin and exit from the sinus node.


Issue bricolage: explaining the configuration of the social movement sector, 1960-1995.
Social movements occupy a shared ideational and resource space, which is often referred to as the social movement sector. This article contributes to the understanding of the relational dynamics of the social movement sector by demonstrating how ideational linkages are formed through protest events. Using a data set of protest events occurring in the United States from 1960 to 1995, the authors model the mechanisms shaping why certain movement issues (e.g., women's and peace or environmental and gay rights) appear together at protest events. They argue that both cultural similarity and status differences between two social movement issues are the underlying mechanisms that shape joint protest and the resultant ideational linkages between issues. Finally, they show that the linking of issues at protest events results in changes in the prominence of a given issue in the social movement sector.


Impact of Bacterial Infections on Osteogenesis: Evidence From In Vivo Studies.
The clinical impact of bacterial infections on bone regeneration has been incompletely quantified and documented. As a result, controversy exists about the optimal treatment strategy to maximize healing of a contaminated defect. Animal models are extremely useful in this respect, as they can elucidate how a bacterial burden influences quantitative healing of various types of defects relative to non-infected controls. Moreover, they may demonstrate how antibacterial treatment and/or bone grafting techniques facilitate the osteogenic response in the harsh environment of a bacterial infection. Finally, it a well-known contradiction that osteomyelitis is characterized by uncontrolled bone remodeling and bone loss, but at the same time, it can be associated with excessive new bone apposition. Animal studies can provide a better understanding of how osteolytic and osteogenic responses are related to each other during infection. This review discusses the in vivo impact of bacterial infection on osteogenesis by addressing the following questions (i) How does osteomyelitis affect the radiographic bone appearance? (ii) What is the influence of bacterial infection on histological bone healing? (iii) How do bacterial infections affect quantitative bone healing? (iv) What is the effect of antibacterial treatment on the healing outcome during infection? (v) What is the efficacy of osteoinductive proteins in infected bones? (vi) What is the balance between the osteoclastic and osteoblastic response during bacterial infections? (vii) What is the mechanism of the observed pro-osteogenic response as observed in osteomyelitis? © 2019 The Authors. Journal of Orthopaedic Research© published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2067-2076, 2019.


Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas.
Multidrug resistance mechanisms underlying the intractability of malignant melanomas remain largely unknown. In this study, we demonstrate that the development of multidrug resistance in melanomas involves subcellular sequestration of intracellular cytotoxic drugs such as cis-diaminedichloroplatinum II (cisplatin; CDDP). CDDP is initially sequestered in subcellular organelles such as melanosomes, which significantly reduces its nuclear localization when compared with nonmelanoma/KB-3-1 epidermoid carcinoma cells. The melanosomal accumulation of CDDP remarkably modulates melanogenesis through a pronounced increase in tyrosinase activity. The altered melanogenesis manifested an approximately 8-fold increase in both intracellular pigmentation and extracellular transport of melanosomes containing CDDP. Thus, our experiments provide evidence that melanosomes contribute to the refractory properties of melanoma cells by sequestering cytotoxic drugs and increasing melanosome-mediated drug export. Preventing melanosomal sequestration of cytotoxic drugs by inhibiting the functions of melanosomes may have great potential as an approach to improving the chemosensitivity of melanoma cells.


The role of crossmatching in organ transplantation.
The preoperative crossmatch is one of the most important laboratory tests in organ transplantation. Quality assurance of this laboratory test depends on a number of factors that include the serum samples and methodology utilized. Clinical correlation with laboratory studies and postoperative outcome of the graft and the recipient are essential to understanding this developing field.


Electrohydrodynamics of an ionic liquid meniscus during evaporation of ions in a regime of high electric field.
Numerical investigations are presented for an ionic liquid meniscus undergoing evaporation of ions in a regime of high electric field. A detailed model is developed to simulate the behavior of a stationary meniscus attached to a liquid feed system. The latter serves as a proxy for commonly utilized electrospray emitters such as needles and capillary tubes. Two solution families are identified for prototype liquid analogous to the ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate (EMI-BF4). The first belongs to a regime of low electric field in which the meniscus is blunt and does not emit charge. The second belongs to a regime of high electric field in which a conelike meniscus produces charge from a sharp tip. Electrohydrodynamic features of the meniscus in this regime are presented. These reveal that the meniscus is Stokesian and hydrostatic and governed by conduction. The applied electric field influences both the shape of the meniscus and the current that it produces while the impedance of the feed system-which must be above a threshold value in order to ensure that the current, and therefore the flow, remains below a maximum value-influences the meniscus current but not the macroscopic shape. In general, this shape deviates from Taylor's idealized cone.


Food choice: beyond the chemical content.
How are food choices formulated? Which are the factors that mostly affect food choice? These questions are crucially important both for efforts in food innovation and for institutions that face consequences and costs of diets that are harmful to human health and to the environment. On these matters, several reports have been developed following the angel of various disciplines, focusing on the analysis of the factors affecting food choices. Large-scale research on consumption behaviours has neither stopped the growing number of unsuccessful products entering the market, nor provided adequate support for institutions that are taking elaborate actions towards promoting health-orientated behaviours. These preliminary remarks highlight the need to think about the approaches and categories with which research programmes on food choices should be updated. This article discusses the reasons why food choices are determined by beliefs and identity, are conditioned by social images that influence preferences by indicating to individuals what foods are 'good' and 'right'; belong to the field of individual choice, and therefore, cannot be assimilated into medical prescriptions or merely reduced to a question of rules. Taste involves beliefs and identity as well as perceptions. This is why it has to be analyzed as a cultural and relational object. This paper aims to explore the complex mix of influences on food choice stressing that food choice is a matter of identity.


Emergency Contraception Counseling in California Community Pharmacies: A Mystery Caller Study.
This study was conducted to determine which emergency contraception (EC) methods are offered by community pharmacists in response to patient calls. Female mystery callers called all community pharmacies in two California cities using standardized scripts. The callers inquired about options available to prevent pregnancy after sex and whether that method was available at the pharmacy, using follow-up probes if necessary. A total of 239 calls were completed in San Diego (n = 127, 53%) and San Francisco (n = 112, 47%). Pharmacists indicated availability at most sites (n = 220, 92%) with option(s) reported as levonorgestrel only (LNG; n = 211, 88.3%), both ulipristal acetate (UPA) and LNG (n = 4, 1.6%), UPA only (n = 1, 0.4%), or non-specific EC (n = 4, 1.7%). Nineteen pharmacies (7.9%) did not have EC available on the day of the call. Following additional probing, some pharmacists discussed UPA (n = 49, 20.5%) or the copper intrauterine device (n = 1, 0.4%) as EC options. LNG EC products were available same-day in 90.1% of pharmacies, whereas UPA was available same-day in 9.6% of pharmacies. The majority of pharmacies called in this study offered and stocked at least one EC option, but the focus of discussions was on LNG and matched what was in stock and available.


[The study on the cloning and expression of alpha toxin gene of clostridium septicum and the immunity of the toxoid].
In order to amplify alpha toxin gene of Clostridium septicum HeB01 strain, one pair of primers was designed according to the GenBank sequence, and a 1323bp alpha toxin gene fragment was obstained by PCR. Sequence analysis indicated that the homology of the nucleotid sequence of HeB01 strain to those other reference strains was more than 99.5% . The expression plasmid pQE30-alpha was constructed by inserting alpha toxin gene into the prokaryotic expression vector pQE30. The plasmid expressed when the recombinant strain M15(pQE30-alpha) was induced by IPTG. The specific 48 kD protein was detected SDS-PAGE and the immunogenicity of the expressed alpha toxin was confirmed by Western blot and ELISA. The expressed alpha toxin was transformed into alpha toxoid vaccine by adding 0.3% formaldehyde into alpha toxin. The protective immune response was proved after the mice was immunized with alpha toxoid vaccine. The results showed that the recombinanted strain M15 (pQE30-alpha) could be as a candidate of alpha toxoid vaccine to provide protective immune response against clostridium septicum infection.


Transcriptome Analysis of Near-Isogenic Lines Provides Novel Insights into Genes Associated with Seed Low-Temperature Germination Ability in Maize (Zea mays L.).
Maize originated from tropical regions and is extremely sensitive to low temperature during germination. Our previous work identified a major QTL, qp1ER1-1, for low temperature germination ability (LTGA) of maize. Here, we introgressed qp1ER1-1 from the tolerant line L220 into the sensitive line PH4CV to generate two near isogenic lines NIL220-3 and NIL220-25. When germinated under cold temperature for 25 days (Cold-25), the NILs showed similar seedling root length and shoot length to L220, but significantly higher than PH4CV. However, when germinated under cold temperature for 15 days (Cold-15) or under normal temperature (25 °C) for 3 days (CK-3), all lines showed similar seedling performance, indicating that introgression of qp1ER1-1 from L220 into PH4CV could improve LTGA of NIL220-3 and NIL220-25. The whole seedlings, including root and shoot, of Cold-15 and CK-3 were harvested for transcriptome analysis, when both stayed at a similar developmental stage. Dry seed embryo was sequenced as a non-germination control (CK-0). Compared with PH4CV, the tolerant line (L220, NIL220-3, and NIL220-25) specifically expressed genes (different expressed genes, DEGs) were identified for CK-0, Cold-15, and CK-3. Then, DEGs identified from Cold-15, but not from CK-0 or CK-3, were defined as tolerant line specifically expressed LTGA genes. Finally, 1786, 174, and 133 DEGs were identified as L220, NIL220-3, and NIL220-25 specifically expressed LTGA genes, respectively. Of them, 27 were common LTGA genes that could be identified from all three tolerant lines, with two (Zm00001d031209 and Zm00001d031292) locating in the confidence interval of qp1ER1-1. In addition, GO analysis revealed that L220 specifically expressed LTGA genes were majorly enriched in the cell division process and plasma membrane related categories. Taken together, these results provided new insight into the molecular mechanism of maize seed LTGA and facilitated the cloning of the qp1ER1-1 gene.


To Stretch the Boundary of Secondary Metabolite Production in Plant Cell-Based Bioprocessing: Anthocyanin as a Case Study.
Plant cells and tissue cultures hold great promise for controlled production of a myriad of useful secondary metabolites on demand. The current yield and productivity cannot fulfill the commercial goal of a plant cell-based bioprocess for the production of most secondary metabolites. In order to stretch the boundary, recent advances, new directions and opportunities in plant cell-based bioprocessing, have been critically examined for the 10 years from 1992 to 2002. A review of the literature indicated that most of the R&D work was devoted predominantly to studies at an empirical level. A rational approach to molecular plant cell bioprocessing based on the fundamental understanding of metabolic pathways and their regulations is urgently required to stimulate further advances; however, the strategies and technical framework are still being developed. It is the aim of this review to take a step forward in framing workable strategies and technologies for molecular plant cell-based bioprocessing. Using anthocyanin biosynthesis as a case study, an integrated postgenomic approach has been proposed. This combines the functional analysis of metabolic pathways for biosynthesis of a particular metabolite from profiling of gene expression and protein expression to metabolic profiling. A global correlation not only can thus be established at the three molecular levels, but also places emphasis on the interactions between primary metabolism and secondary metabolism; between competing and/or complimentary pathways; and between biosynthetic and post-biosynthetic events.


Sister chromatid exchange in lymphocytes of agricultural workers exposed to pesticides.
Sister chromatid exchange (SCE) was studied in the lymphocytes of 27 agricultural workers occupationally exposed to several pesticides and 28 matched controls from el Maresme, an agricultural area near Barcelona. Comparison between both groups with the t-test did not reveal significant differences. These negative findings suggest that, possibly, the exposure level is too low to increase SCE in human lymphocytes in vivo. Our results indicate that smokers, both the workers and the controls, had a higher SCE frequency than non-smokers, in agreement with previous data reported by different authors.


Mechanisms of TGF-beta1-induced intimal growth: plasminogen-independent activities of plasminogen activator inhibitor-1 and heterogeneous origin of intimal cells.
Transforming growth factor (TGF)-beta(1) is a potent stimulator of intimal growth. We showed previously that TGF-beta(1) stimulates intimal growth through early upregulation of plasminogen activator inhibitor-1 (PAI-1) and, subsequently, PAI-1-dependent increases in cell migration and matrix accumulation. We also showed that PAI-1 negatively regulates TGF-beta(1) expression in the artery wall. Here we use plasminogen-deficient mice to test whether TGF-beta(1)-stimulated, PAI-1-dependent intimal growth and PAI-1 suppression of TGF-beta(1) expression are mediated through inhibition of plasminogen activation by PAI-1. We also use lineage tracing to investigate the origin of cells in TGF-beta(1)-induced intimas. Surprisingly, both TGF-beta(1)-induced, PAI-1-dependent intimal growth and PAI-1 suppression of TGF-beta(1) expression are independent of plasminogen. Moreover, approximately 50% of cells that migrate into the intima of TGF-beta(1)-overexpressing arteries carry a smooth muscle lineage marker, <1% carry a bone marrow lineage marker, and the remaining cells carry neither marker. Therefore, PAI-1 stimulates intimal growth and suppresses TGF-beta(1) expression through activities other than inhibition of plasminogen activation. In addition, contrary to widely held models, our results do not support a role for plasmin (or thrombospondin) in TGF-beta(1) activation in the artery wall. Further identification of the molecular targets through which PAI-1 stimulates intimal formation and suppresses TGF-beta(1) expression in the artery wall may reveal new approaches for inhibiting intimal formation. Our studies also discount bone marrow as an important source from which TGF-beta(1) recruits intimal cells and suggest instead that TGF-beta(1) induces substantial cell migration either from the adventitia or from an extravascular, but nonhematopoietic source.


Association of dietary fiber intake with hyperuricemia in U.S. adults.
Current evidence on the relationship between dietary fiber intake and risk of hyperuricemia is limited. The aim of the present study was to examine their associations in the U.S. general adult population. Data from the National Health and Nutrition Examination Survey (NHANES) 2009 to 2014 were used. Dietary fiber intake was extracted through two 24 h dietary recall interviews. Hyperuricemia was defined by cut-off values of 7.0 mg dL-1 for men and 6.0 mg dL-1 for women. Multivariable logistic regression models and restricted cubic spline models were applied to explore the associations between dietary intakes of total, cereal, fruit and vegetable fiber and the risk of hyperuricemia. A total of 12 869 participants aged 20 years or older were included in the present study. The multivariable odds ratio (OR) and 95% confidence interval (CI) of hyperuricemia for the highest vs. lowest quartile intake of total fiber were 0.58 (0.46-0.74), 0.61 (0.52-0.74) for cereal fiber, 0.94 (0.76-1.16) for fruit fiber and 0.95 (0.76-1.18) for vegetable fiber. The inverse associations between dietary intakes of total fiber and cereal fiber and the risk of hyperuricemia were observed in men. In stratified analysis by age (<45 years, ≥45 years), the inverse association between total fiber intake and the risk of hyperuricemia was consistent, while cereal fiber intake was only inversely associated with hyperuricemia among participants <45 years old. Dose-response analyses showed that the risk of hyperuricemia was associated with dietary intake of total fiber in a nonlinear manner, whereas the relationship was linear for cereal fiber intake. In conclusion, dietary intakes of total fiber and cereal fiber were inversely associated with the risk of hyperuricemia in the U.S. adult population.


Rickettsia asembonensis Characterization by Multilocus Sequence Typing of Complete Genes, Peru.
While studying rickettsial infections in Peru, we detected Rickettsia asembonensis in fleas from domestic animals. We characterized 5 complete genomic regions (17kDa, gltA, ompA, ompB, and sca4) and conducted multilocus sequence typing and phylogenetic analyses. The molecular isolate from Peru is distinct from the original R. asembonensis strain from Kenya.


Allergic arthritis induced by cationic proteins: role of molecular weight.
Previous studies have shown that chronic murine allergic arthritis can only be induced with cationized BSA, related to excellent retention of the cationic antigen in the joint. We now investigate the impact of size of cationic proteins on their potential to induce this form of arthritis. After intra-articular injection, antigen retention is much enhanced with high molecular weight cationized proteins, like albumin or immunoglobulin, compared to small-sized proteins like myoglobulin and lysozyme. Consequently, severe chronic arthritis was only found with the former ones. The role of size is further substantiated with poly-L-lysine-coupled lysozyme. This derivative shows excellent retention in vivo and causes a chronic destructive arthritis in preimmunized mice, in contrast to the poor arthritis seen with native cationic lysozyme. Control experiments made it clear that antigen retention is the most important denominator and that differences in chronicity are not related to gross variations in T-cell reactivity. Retention studies in vitro revealed that the potential to bind to joint structures is similar for the various proteins, suggesting that in vivo conditions determine size-related differences in antigen clearance. Our data indicate that cationicity per se does not make a protein a proper arthritogen.


Serotonin Transporter Binding in the Human Brain After Pharmacological Challenge Measured Using PET and PET/MR.
Introduction: In-vivo quantification of the serotonin transporter (SERT) guided our understanding of many neuropsychiatric disorders. A recently introduced bolus plus constant infusion protocol has been shown to allow the reliable determination of SERT binding with reduced scan time. In this work, the outcomes of two methods, a bolus injection paradigm on a GE PET camera, and a bolus plus infusion paradigm on a combined Siemens PET/MR camera were compared. Methods: A total of seven healthy subjects underwent paired PET and paired PET/MR scans each with intravenous double-blind application of 7.5 mg citalopram or saline in a randomized cross-over study design. While PET scans were performed according to standard protocols and non-displaceable binding potentials (BPND) were calculated using the multi-linear reference tissue model, during PET/MR measurements [11C]DASB was applied as bolus plus constant infusion, and BPND was calculated using the steady state method and data acquired at tracer equilibrium. Occupancies were calculated as the relative decrease in BPND between saline and citalopram scans. Results: During placebo scans, a mean difference in BPND of -0.08 (-11.71%) across all ROIs was found between methods. PET/MR scans resulted in higher BPND estimates than PET scans in all ROIs except the midbrain. A mean difference of -0.19 (-109.40%) across all ROIs between methods was observed for citalopram scans. PET/MR scans resulted in higher BPND estimates than PET scans in all ROIs. For occupancy, a mean difference of 23.12% (21.91%) was observed across all ROIs. PET/MR scans resulted in lower occupancy compared to PET scans in all ROIs except the temporal cortex. While for placebo, BPND of high-binding regions (thalamus and striatum) exhibited moderate reliability (ICC = 0.66), during citalopram scans ICC decreased (0.36-0.46). However, reliability for occupancy remained high (0.57-0.82). Conclusion: Here, we demonstrated the feasibility of reliable and non-invasive SERT quantification using a [11C]DASB bolus plus constant infusion protocol at a hybrid PET/MR scanner, which might facilitate future pharmacological imaging studies. Highest agreement with established methods for quantification of occupancy and SERT BPND at baseline was observed in subcortical high-binding regions.


Genome-Wide Repertoire of Transfer RNA-Derived Fragments in a Mouse Model of Age-Related Cataract.
To investigate the roles of tRNA-derived small RNAs (tsRNAs) containing transfer RNA-derived fragments (tRFs) and tRNA halves in age-related cataracts (ARCs). Lens capsule tissue from Emory mice at 3 months and 8 months of age were dissected for integrated tsRNA and gene transcriptome sequencing. A quantitative real-time PCR assay (qRT-PCR) was performed for validating sequencing results. Bioinformatics analysis was constructed to reveal the roles of tsRNAs. A total of 422 differential expression (DE) tsRNAs were changed, in which 156 were elevated while 266 were declined in 8-month-old mice. Subsequently, the gene sequencing data exhibited 375 upregulated and 456 downregulated DE genes. Validation by qRT-PCR in 5 selected upregulated tRFs was consistent with tsRNAs sequencing results. Moreover, bioinformatics analysis identified 25 downregulated target genes of the 5 validated tRFs. Furthermore, GO analysis revealed that these target genes were mainly enriched in camera-type eye development, sensory organ development, and so on. Our study provides a novel perspective on the role of tsRNAs in the pathogenesis of ARC, and thus therapeutic potential targets for ARC.


Isolation, purification, characterization, and immunomodulatory effects of polysaccharide from Auricularia auricula on RAW264.7 macrophages.
Auricularia auricula polysaccharide (AAP) was isolated by hot-water extraction and purified to evaluate its structural and immunomodulatory effects on RAW264.7 macrophages. The results show that three kinds of Auricularia auricula polysaccharides (c-AAP) were obtained and named as AAP-I, AAP-II, and AAP-III Their further purification found that AAP-I and AAP-II were glycoproteins, and only AAP-III was a pure polysaccharide, which we named AAP for further experiments. Structural characteristics revealed that AAP was a homogeneous galactan comprising mannose, rhamnose, gluconic acid, glucose, galactose, arabinose, and fucose in a molar ratio of 5.02:0.9:0.12:4.48:0.37:1.0:0.36, and the average molecular weight is approximately 23.51 kDa. Methylation analysis revealed that AAP mainly consisted of 1,4-linked-Glcp, 1,4,6-linked-Glcp, terminal Glcp, 1,4-linked-Manp, 1,2,6-linked-Manp, and terminal Arap. Furthermore, the in vitro immunomodulatory activities of AAP were evaluated by cell proliferation, NO production, and phagocytic ability using RAW264.7 macrophage cells. The results show that AAP not only promoted the activation of macrophages but also provided a scientific basis for the further use of AAP. PRACTICAL APPLICATIONS: Three water-soluble polysaccharides were extracted from Auricularia auricula of Changbai Mountain, two of which contained binding proteins. Determination of molecular weight, structure, and immunoreactivity of pure polysaccharide components. The result clearly demonstrated the benefits of this plant as a healthy functional food.


Optical Patterning of Two-Dimensional Materials.
Recent advances in the field of two-dimensional (2D) materials have led to new electronic and photonic devices enabled by their unique properties at atomic thickness. Structuring 2D materials into desired patterns on substrates is often an essential and foremost step for the optimum performance of the functional devices. In this regard, optical patterning of 2D materials has received enormous interest due to its advantages of high-throughput, site-specific, and on-demand fabrication. Recent years have witnessed scientific reports of a variety of optical techniques applicable to patterning 2D materials. In this minireview, we present the state-of-the-art optical patterning of 2D materials, including laser thinning, doping, phase transition, oxidation, and ablation. Several applications based on optically patterned 2D materials will be discussed as well. With further developments, optical patterning is expected to hold the key in pushing the frontiers of manufacturing and applications of 2D materials.


Retrospective diagnosis: use and abuse in medical historiography.
Medical papers on diseases of famous persons, sometimes called pathographies, constitute the by far largest section of publications dealing with historical diagnosis. The procedure of attaching modern diagnostic labels to illustrious personalities of the past, i.e. retrospective diagnosis, has stimulated an ongoing theoretical debate among clinicians and medical historians. The purpose of this paper is to clarify some of the issues involved. Key problems of retrospective diagnostics are reviewed and analysed. In addition, the case history of the Polish composer Fryderyk Chopin is used to highlight problems and pitfalls of this method. Whereas contemporary physicians are used to apply present-day nosological categories to individuals of the past or historical epidemics, medical historians are more cautious to do so. They argue that in the absence of definite proofs retrospective diagnoses often are nothing more than mere speculation. Another important counter-argument is that medical knowledge itself varies over time and historical changes in nosology must not be ignored. Future pathographies should use primary sources extensively, focus on historical context and minimize the pursuit of retrospective diagnoses or causes of death. Only with a fundamentally revised method, a more critical approach to retrospective diagnostics, and far more serious objectives will medical biographies be in a position to break new ground.


Mastoid obliteration: autogenous cranial bone pAte reconstruction.
To review the outcome in consecutive patients who have undergone complete epitympanic and mastoid obliteration and concurrent tympanic membrane reconstruction over a 53-month period. Retrospective review. Tertiary referral center. Sixty-two ears in 56 sequential patients undergoing mastoid obliteration with major indications including recurrent infection, debris trapping in the canal wall-down cavity, intolerance of water exposure, calorically induced vertigo in an existing cavity, a semicircular canal fistula, and inability to wear a hearing device. Thirty-six ears in 33 patients who underwent second-stage surgery for ossicular reconstruction during the same time period are also reviewed. Transplanted autogenous cranial bone is used to induce osteoneogenesis resulting in complete obliteration of the epitympanic and mastoid spaces while maintaining a mesotympanic space. Success of obliteration, incidence of symptoms prompting intervention, hearing outcome, incidence of recurrent cholesteatoma, and incidence of eustachian tube dysfunction necessitating treatment and need for revision surgical procedures.RESULTS Complete take of the bony obliteration occurs in over 95% of cases; 90% of treated patients enjoy complete absence of original symptoms, whereas symptoms improved in the remainder. For over 95% of patients, existing eustachian tube function has been adequate after obliteration. To date, no patient has required revision surgical intervention. Mastoid obliteration with autogenous cranial bone is a safe and extremely effective option for treatment of problematic canal wall-down mastoid cavities. Surgical techniques that include sterile harvest of the cranial bone graft mixed with antibiotic, revision of the cavity to expose viable native bone, inclusion of the epitympanic spaces in the obliteration, and complete coverage of the pAte with autogenous fascia have proven critical to successful outcome.


Cholesterol distribution, not total levels, correlate with altered amyloid precursor protein processing in statin-treated mice.
There are now a number of studies that suggest that cholesterol might regulate the processing of the amyloid precursor protein to form the neurotoxic peptide Abeta. This research has opened the possibility that cholesterol-lowering drugs might be efficacious as anti-Abeta drugs for use in Alzheimer's disease. The use of HMG-CoA reductase inhibitors (commonly called statins) in vitro and in vivo has proven them to be Abeta-lowering agents, however, the mechanism of action of these drugs is not yet known. One possible mechanism is that they reduce Abeta levels indirectly by reducing cholesterol in the central nervous system (CNS). In this study, we administered three different statins (simvastatin, lovastatin, and atorvastatin) to nontransgenic mice. We found that all three compounds had similar effects on Abeta, reducing both Abeta40 and Abeta42. The statins decreased beta-cleaved C-terminal fragment (CTF) although having no effect on alpha-CTF levels. However, the drugs did not have a similar effect on cholesterol in the CNS. Only lovastatin significantly reduced total cholesterol in isolated plasma membranes. As cholesterol is not distributed evenly in the plasma membrane, we examined bilayer distribution of cholesterol and found that all three statins caused CNS cholesterol to translocate from the cytofacial leaflet to the exofacial leaflet. This data suggests that cholesterol distribution and not total cholesterol levels may be important to Abeta production in the CNS.


Expression of cytokeratins and vimentin in normal and neoplastic tissue from the bovine female reproductive tract.
The distribution of cytokeratins (CKs) and vimentin in the normal genital tract of calves and cows at different stages of the oestrous cycle and in epithelial tumours of the tract was studied immunohistochemically. Few differences in CK and vimentin immunolabelling were detected in relation to age or stage of the oestrous cycle. Coexpression of CKs in simple epithelia and in basal cells of stratified epithelia was detected in the oviduct and endocervix; this coexpression was different from that previously described in women. The demonstration of CKs but not vimentin in the neoplastic cells of a serous superficial ovarian papilloma suggested an origin from the ovarian surface epithelium, while the coexpression of CKs and vimentin in serous papillary and mucinous cystadenomas pointed to a possible origin from the rete ovarii. Studies on three uterine adenocarcinomas and the ovarian metastases from two of these showed an endometrial-CK phenotype. The intermediate filament profile of normal endometrium, conserved in uterine adenocarcinomas and their ovarian metastases, may be useful in discriminating between ovarian metastases from endometrial carcinomas and those originating from primary carcinomas in other organs.


The diagnosis of strep throat in adults in the emergency room.
Adult patients who presented to an urban emergency room complaining of a sore throat had cultures and clinical information recorded. Models were constructed, using logistic regression analysis, of both a positive culture for Group A beta streptococcus and a positive guess by a resident. The model of a positive culture consisted of four variables--tonsillar exudates, swollen tender anterior cervical nodes, lack of a cough, and history of fever. Patients with all 4 variables had a 56% probability of a positive culture; 3 variables, 32%; 2 variables, 15%; 1 variable, 6.5%; and 0 variables, 2.5%. The model of a positive guess by a resident demonstrated an over-reliance on physical exam and an underuse of history. The model of a positive culture allows stratification of patients to assist clinicians in the management strategies.


Cytotoxic T Lymphocyte Antigen 4 Haploinsufficiency Presenting As Refractory Celiac-Like Disease: Case Report.
Primary immunodeficiency may present with treatment-refractory enteropathy. We present two patients with celiac/celiac-like disease diagnosed in early childhood and refractory to the gluten-free diet. One patient had features of multi-system autoimmunity, whereas the other had celiac-like disease as an isolated clinical finding. Both patients underwent genetic testing given disease refractoriness and were ultimately diagnosed with cytotoxic T lymphocyte antigen 4 (CTLA4) haploinsufficiency. They are both now in complete clinical and endoscopic remission on abatacept. CTLA4 haploinsufficiency has incomplete penetrance and significant phenotypic heterogeneity but should be considered in the differential diagnosis of refractory celiac/celiac-like disease, as treatment implications are significant.


Effects of 50 Hz sinusoidal magnetic fields on Hsp27, Hsp70, Hsp90 expression in porcine aortic endothelial cells (PAEC).
The aim of the present study was to investigate the influence of 50 Hz sinusoidal magnetic field on Hsp27, Hsp70, and Hsp90 expression in a model of primary culture of porcine aortic endothelial cells (PAEC). We took into consideration the Hsp profile in terms of mRNA expression, protein expression and protein localization inside the cells. The choice of the cell system was motivated by the involvement of the endothelial cells in the onset of many diseases; moreover, only few reports describe the effects of extremely low frequency magnetic fields (ELF-MFs) on such cells. ELF-MF exposure induced an increase in the mRNA levels of the three proteins, which was statistically significant for Hsp70. On the contrary, we did not observe any influence on Hsp27, Hsp70, and Hsp90 protein levels. Analysis in situ by immunofluorescence revealed that ELF-MF exposure affected the cellular distribution of Hsp27; in particular a partial relocalization in the nucleus was observed.


Independent dosimetric assessment of the model EP917 episcleral brachytherapy plaque.
To investigate the influence of slot design on dose distributions and dose-volume histograms (DVHs) for the model EP917 plaque for episcleral brachytherapy. Dimensions and orientations of the slots were measured for three model EP917 plaques and compared to data in the Plaque Simulator (PS) treatment planning software (version 5.7.6). These independently determined coordinates were incorporated into the MCNP Monte Carlo simulation environment to obtain dose from the plaques in a water environment and in a clinical environment with ocular structures. A tumor volume was simulated as 5 mm in apical height and 11 mm in basal diameter. Variations in plaque mass density and composition; slot length, width, and depth; seed positioning; and Ag-marker rod positioning were simulated to examine their influence on plaque central axis (CAX) and planar dose distributions, and DVHs. Seed shifts in a single slot toward the eye and shifts of the(125)I-coated Ag rod within the capsule had the greatest impact on CAX dose distribution. A shift of 0.0994 mm toward the eye increased dose by 14%, 9%, 4.3%, and 2.7% at 1, 2, 5, and 10 mm, respectively, from the inner sclera. When examining the fully-modeled plaque in the ocular geometry, the largest dose variations were caused by shifting the Ag rods toward the sclera and shifting the seeds away from the globe when the slots were made 0.51 mm deeper, causing +34.3% and -69.4% dose changes to the outer sclera, respectively. At points along the CAX, dose from the full plaque geometry using the measured slot design was 2.4%±1.1% higher than the manufacturer-provided slot design and 2.2%±2.3% higher than the homogeneous calculation of PS treatment planning results. The ratio of D10 values for the measured slot design to the D10 values for the manufacturer-provided slot design was higher by 9%, 10%, and 19% for the tumor, inner sclera, and outer sclera, respectively. In comparison to the measured slot design, a theoretical plaque having narrower and deeper slots delivered 30%, 37%, and 62% lower D10 doses to the tumor, inner sclera, and outer sclera, respectively. While the measured positions of the slots on the model EP917 plaque were in close agreement (<0.7 mm) with the PS values, small differences in the slot shape caused substantial differences in dose distributions and DVH metrics. Increasing slot depth by 0.1 mm decreased outer scleral dose by 20%, yet shifting the Ag rods in the seeds toward the globe by 0.1 mm increased outer scleral dose by 35%. The clinical medical physicist is advised to measure these types of plaques upon acceptance testing before clinical use to inspect slot shape and position for comparison with data used for treatment planning purposes.


Lumbar Microdiscectomy.
In most patients, the radiculopathy associated with lumbar disc herniation resolves nonoperatively. For patients in whom nonsurgical management has failed, microdiscectomy can be considered. Today, an operating microscope is preferred because of the collinear light and magnification offered. Alternatively, loupes and a headlight may be employed. The major steps of the procedure are (1) making a 2-cm vertical incision and then developing the corridor to the lamina subperiosteally or by using serial dilation techniques; (2) confirming the level of surgery radiographically prior to incision and once the lamina has been reached and then detaching the lateral attachments of the flavum; (3) making a small laminotomy, resecting any superior facet osteophytes, then mobilizing the compressed traversing nerve root, and, in some cases, making a small annulotomy; and (4) removing loose disc fragments and performing wound closure. Most outcomes reports after microdiscectomy have been favorable for radicular symptoms. Associated back pain typically decreased as well. Common complications include recurrent disc herniation or disc herniation at another level, wound infections, and durotomy with spinal headache.


[Cytogenetic analysis of 19 renal cell tumors].
To further evaluate the role of cytogenetic analysis we studied 19 cases of renal neoplasms. Specific chromosomal aberrations have been demonstrated associated with different histologic types. Particularly, clear cell renal cancers were associated with deletions of the short arm of chromosome 3 and papillary renal cell cancers demonstrated multiple trisomies, and chromophobe cancers and oncocytomas were characterized by loss of whole chromosomes. The utility of cytogenetics as a tool to define the pathological spectrum of renal cell neoplasms is stressed.


Online prescribing of sildanefil (Viagra) on the world wide web.
A growing number of prescription medicines such as Viagra are offered and sold directly to consumers on the Internet. Little is known about the structure and "quality" of these "virtual pharmacies" in terms of how responsibly "online-prescriptions" are actually issued. To determine to what extent Viagra is sold on the Internet despite clear contraindications. The World Wide Web was searched for companies who offer to issue prescriptions for Viagra online or sell Viagra without prescription. We pretended to be a patient in which the ordered drug (Viagra) is clearly contraindicated, and tried to obtain an online prescription for this drug on the Internet. Our test case was as a 69-year-old woman giving a sexual history of having "no orgasm," with obesity (165 cm/78 kg), coronary artery disease, and hypertension, and taking captopril, pravachol, atenolol, and erythromycin. Twenty-two distinct companies were identified, consisting of three different types: 2 required a written prescription by a "real" physician, 9 dispensed the drug without any prescription at all, and 11 issued an "online prescription" after an alleged physician reviewed the online order form containing medical questions. We tested 10 of the latter type, among them 8 based in the USA. We ordered a total of 66 pills worth US$ 1,802.84. Three companies, among them both European companies, delivered within 6, 10, and 34 days respectively, despite Viagra being clearly contraindicated. In 80% no complete history was taken, in 70% inappropriate medical terminology was used, and in only 2 cases was the order form reviewed by a physician who identified himself. Although a surprisingly high number of Internet pharmacies declined delivery, the public should be alerted to the risks involved with prescription drug prescribing and dispensing via the Internet.


Genital Chlamydia trachomatis infection in women.
Specimens for isolation of Neisseria gonorrhoeae, Chlamydia trachomatis, Candida albicans, and Trichomonas vaginalis were collected from 585 women attending clinics for venereal diseases. The isolation rates in women attending clinics for venereal diseases. The isolation rates in women with and without genitourinary symptoms, the course of untreated chlamydial infection, the occurrence of chlamydial urethritis, and the response to antibiotic treatment were investigated. A 30% incidence of chlamydial amd gonococcal infection was observed. In most cases the gonococcal infection affected both the cervix and the urethra, whereas the chlamydial infection was restricted to either the cervix or the urethra. Sampling of secretions from the urethra revealed chlamydial infections (15%) that otherwise would have remained undetected. In untreated cases chlamydiae persisted for at least 6 weeks. Bacteriologically, chlamydial infections responded equally well to doxycycline, erythromycin, and a combination of trimethoprim and sulfamethoxazole. however, symptoms persisted in 34% of the women.


[Alternative promoters and oct-1 gene tissue-specific regulation].
Murine oct-1 gene contains exons IU and 1L at 5'-end, which are alternatively presented in oct-1 mRNA. 1U exon is presented in oct-1 mRNA expressed in all tissues whereas lymphoid cells of mouse and human express mRNA containing alternatively IU or 1L exon. Upstream of these exons there are U and L promoters, respectively, which are separated by 67 kb in mice otf-1 locus. Nucleotide sequences located upstream 1U and 1L exons are very different: IU region contains a number of Sp1 sites and 1L region contains many homeo-specific sites and two octamers ATGCAAAT recognized by transcription factors Oct-1, Oct-2 and other POU-domain containing proteins. Oct-1 sites may participate in oct-1 gene autoregulation. The role of U- and L-promoter fragments in oct-1 gene regulation was studied by transfection of luc-containing constructs in lymphoid (NS/0) and non-lymphoid cells. It was shown that L-promoter efficiency is much higher in lymphoid cells than in fibroblast cell line 10/1. U-promoter is active in both types of the cells. Upstream of IL-exon there is the inhibitory nucleotide sequence which elimination increases the expression level by many times. This silencing element is located between initiation starts of transcription and translation. The obtained data suggest that oct-1 gene contains at least two alternative promoters. It seems that U-promoter promises the constitutive synthesis of Oct-1 protein whereas L-promoter is tissue-specific and putatively is inducible and autoregulated.


Quaternized α,α'-Amino Acids via Curtius Rearrangement of Substituted Malonate-Imidazolidinones.
An efficient synthesis protocol is presented for accessing quaternized α-amino acids in chiral, nonracemic form via diastereoselective malonate alkylation followed by C- to N-transposition. The key stereodifferentiating step involves a diastereoselective alkylation of an α-monosubstituted malonate-imidazolidinone, which is followed first by a chemoselective malonate PMB ester removal and then a Curtius rearrangement to provide the transposition. The method demonstrates a high product ee (89-99% for eight cases) for quaternizing a range of proteinogenic α-amino acids. The stereogenicity in targets 5a-i supports previous conclusions that the diastereoselective alkylation step proceeds via an α-substituted malonate-imidazolidinone enolate in its Z-configuration, with the auxiliary in an s-transC-N conformation.


Calpain inhibition by alpha-ketoamide and cyclic hemiacetal inhibitors revealed by X-ray crystallography.
Calpains are intracellular calcium-activated cysteine proteases whose unregulated proteolysis following the loss of calcium homeostasis can lead to acute degeneration during ischemic episodes and trauma, as well as Alzheimer's disease and cataract formation. The determination of the crystal structure of the proteolytic core of mu-calpain (muI-II) in a calcium-bound active conformation has made structure-guided design of active site inhibitors feasible. We present here high-resolution crystal structures of rat muI-II complexed with two reversible calpain-specific inhibitors employing cyclic hemiacetal (SNJ-1715) and alpha-ketoamide (SNJ-1945) chemistries that reveal new details about the interactions of inhibitors with this enzyme. The SNJ-1715 complex confirms that the free aldehyde is the reactive species of the cornea-permeable cyclic hemiacetal. The alpha-ketoamide warhead of SNJ-1945 binds with the hydroxyl group of the tetrahedral adduct pointing toward the catalytic histidine rather than the oxyanion hole. The muI-II-SNJ-1945 complex shows residue Glu261 displaced from the S1' site by the inhibitor, resulting in an extended "open" conformation of the domain II gating loop and an unobstructed S1' site. This conformation offers an additional template for structure-based drug design extending to the primed subsites. An important role for the highly conserved Glu261 is proposed.


Corticofugal reorganization of the midbrain tonotopic map in mice.
Previous studies have indicated that frequency maps (tonotopies) in mammalian auditory brain centers are plastic. Here, we examined this plasticity in the mouse auditory midbrain through focal stimulation of the primary auditory cortex. Cortical activation shifted midbrain frequency tunings toward the best frequencies of the stimulated cortical neurons if these were either higher or lower than the cortical ones. Such corticofugal adjustments appear to minimize the difference between cortical and collicular frequency tuning within the critical bandwidths of the auditory system. Consequently, the neural representation is enhanced for the frequencies to which the cortical neurons were tuned. Our data suggest that the auditory cortex reorganizes midbrain tonotopy on the basis of which cortical frequencies are stimulated, mostly probably through corticofugal projections.


[Dental status among schoolchildren in Kaunas and analysis of oral health care].
The prevalence of dental caries is very high (98%) among schoolchildren in Lithuania. Effective prevention, early diagnostics, and appropriate treatment of the disease will guarantee good oral health, proper functioning of the dentition. The aim of the present study was to assess the oral status in 7-, 12- and 15-year-old schoolchildren in Kaunas as well as to define the methods of oral health care, quality of the restorations, opinion of the heads of the clinics concerning the oral health care in their institutions. A total of 586 children were examined. The questionnaires were filled out by the heads of the private clinics and primary health care centers. Oral health status was evaluated according to the criteria of World Health Organization. Results of the study showed that the prevalence of dental caries increased with the age of the children ranging from 20.6% among 7-year-olds up to 95.9% among 15-year-olds. The need for dental treatment was found in 38.9% of 7-year-olds and 51.8% of 15-year-olds; 3.8% were in need of prosthodontic treatment. More than a half of fillings (52.5%) were of good quality, and 47.5% had to be replaced. Private clinics had better dental equipment (81.8%) in comparison with the primary health care centers (55.0%). Better instruments and materials were in private clinics (86.4%) than in primary health care centers (40.0%). According to the answers, the heads of the clinics and centers think that better dental service for the patients might be given by better financing of the institutions and effective prevention of dental caries.


The Association of Early Life Factors and Declining Incidence Rates of Dementia in an Elderly Population of African Americans.
To explore the possible association of childhood residence, education levels, and occupation with declining incidence rates of dementia in 2 cohorts of elderly African Americans. African Americans residing in Indianapolis without dementia were enrolled in 1992 and 2001 and evaluated every 2-3 years. The cohorts consist of 1,440 participants in 1992 and 1,835 participants in 2001 aged 70 years and older. Cox proportional hazard regression models were used to compare cohort differences in dementia and Alzheimer's disease (AD) risk. The 2001 cohort had significantly decreased risk of both incident dementia and AD (hazard ratio [HR]: 0.62/0.57 for dementia/AD). Years of education was associated with decreased risk of dementia (HR = 0.93; p = .0011). A significant interaction (p = .0477) between education and childhood rural residence was found for the risk of AD that higher education level is significantly associated with reduced AD risk (HR = 0.87) in participants with childhood rural residence, but no association in those with urban upbringing. The cohort difference for dementia rates were attenuated by adjusting for the 3 risk factors but remained significant (HR = 0.75; p = .04). These results emphasize the importance of early life factors including rural residence and education for the risk for dementia later in life.


[Gastric mucormycosis in an immunocompetent child].
Mucormycosis is a rare, usually fatal, opportunistic infection that mostly affects people with immune deficiency or associated pathologies. There are few reports of this disease in patients without the traditional risk factors, still unknown what could be the real predisposing causes involved. The forms of presentation are rhinocerebral, cutaneous, pulmonary, gastrointestinal and disseminated. This is why, due to the difficult diagnosis, high mortality and uncommon presentation, we report the case of a 4-year-old child without immunodeficiency or background pathologies who developed an esophagogastric mucormycosis.


Risk-taking, responsibility for health, and attitude toward avoiding AIDS.
A telephone survey was completed with 400 adults to explore a possible relation between health risk-taking and perceived personal responsibility for health. The attitude that AIDS could be avoided by being careful was weakly associated with responses to questions about wearing seat belts and smoking. The pattern held only among those who thought their health was good for people their age. After reviewing related literature, it appears that poor health status and dogmatism may contribute to denial of risk and to risky sexual behavior. Themes for public health educational campaigns are suggested.


Primary signet‑ring cell melanoma of the anorectum: A case report.
Malignant melanoma is one of the most common malignant tumors. Although its incidence rate is generally low among the Chinese population, it has grown rapidly in recent years. The incidence of primary malignant melanoma in the digestive tract is very low. The incidence in the esophagus and rectum are more common, while reports in the colon are only reported in <10 cases. Primary signet ring cell carcinoma of the rectum is also a rare and unique tumor. This paper reports a case of rectal malignant melanoma with signet ring cell carcinoma.


MUC-1 mucin protein expression in B-cell lymphomas.
We have recently shown that MUC1, mapped to the chromosomal band 1q21, is rearranged or amplified in 15% of B-cell lymphomas and that rearrangement led to over-expression of MUC-1 mucin in a case of diffuse large B-cell lymphoma (DLBCL). To determine the incidence of MUC-1 mucin expression and its clinical significance in B-cell lymphomas, we investigated a panel of 113 cases by immunohistochemistry (IHC). MUC-1 mucin expression was detected in the majority of cases (92.9%), with moderate to high levels noted in 50.4% of all histologic subsets comprising DLBCL (82 cases), follicular lymphoma (FL) (15 cases), FL with transformation to DLBCL (4 cases), and other B-cell lymphomas (12 cases). No statistically significant correlation was found between MUC-1 mucin expression and MUC1 genomic status (amplification/rearrangement) evaluated by Southern blot analysis, and 1q21 abnormality by karyotypic analysis. For all cases, MUC-1 mucin expression correlated with a previous history of lymphoma (p=0.003).


Transfusion-related acute hepatic injury following postoperative platelets administration in pediatric patients undergoing the Fontan procedure.
The final common pathway of single ventricle patients is the Fontan procedure. Among the immediate postoperative complications is acute hepatic injury presented by marked elevation of liver enzymes (alanine transaminase [ALT] and aspartate transaminase [AST]). We aimed to determine the contribution of blood products transfusion to acute hepatic injury. Single center retrospective cohort study. Pediatric Cardiac Intensive Care Unit at a tertiary medical center. Ninety-nine pediatric patients undergoing the Fontan procedure between January 2009 and December 2016. None. Out of the four types of blood products, transfusion of platelets was found to significantly affect postoperative levels of ALT and AST. Additional factors included postoperative administration of sodium bicarbonate, decreased flow through the Fontan canal and decreased urine output. Preoperative pulmonary artery pressure and pulmonary vascular resistance, cardiopulmonary bypass time, aortic cross-clamp time, amount of postoperative bleeding, and vasoactive-inotropic score did not influence liver enzymes levels CONCLUSIONS: In pediatric Fontan patients, platelets transfusions contribute to an acute hepatic injury. The relation between platelets and transfusion-related acute lung injury (TRALI) has been well described, but this is the first time it is being described in regard to acute hepatic injury (TRAHI). Changing platelet transfusion strategy could decrease morbidity in Fontan patients but further research is needed.


Neuronal brain-derived neurotrophic factor is synthesized in excess, with levels regulated by sortilin-mediated trafficking and lysosomal degradation.
Brain-derived neurotrophic factor (BDNF) regulates neuronal differentiation, synaptic plasticity, and morphology, and modest changes in BDNF levels results in complex behavioral phenotypes. BDNF levels and intracellular localization in neurons are regulated by multiple mechanisms, including use of distinct promoters, mRNA and protein transport, and regulated cleavage of proBDNF to mature BDNF. Sortilin is an intracellular chaperone that binds to the prodomain of BDNF to traffic it to the regulated secretory pathway. However, sortilin binds to numerous ligands and plays a major role in mannose 6-phosphate receptor-independent transport of lysosomal hydrolases utilizing motifs in the intracellular domain that mediate trafficking from the Golgi and late endosomes. Sortilin is modified by ectodomain shedding, although the biological implications of this are not known. Here we demonstrate that ADAM10 is the preferred protease to cleave sortilin in the extracellular stalk region, to release the ligand binding sortilin ectodomain from the transmembrane and cytoplasmic domains. We identify sortilin shedding at the cell surface and in an intracellular compartment. Both sortilin and BDNF are trafficked to and degraded by the lysosome in neurons, and this is dependent upon the sortilin cytoplasmic tail. Indeed, expression of the sortilin ectodomain, which corresponds to the domain released after shedding, impairs lysosomal targeting and degradation of BDNF. These findings characterize the regulation of sortilin shedding and identify a novel mechanism by which sortilin ectodomain shedding acts as a regulatory switch for delivery of BDNF to the secretory pathway or to the lysosome, thus modulating the bioavailability of endogenous BDNF.


Cerebral oligaemia episode triggers free radical formation and late cognitive deficiencies.
Sixty minutes of cerebral oligaemic hypoxia, induced by bilateral clamping of the carotid arteries (BCCA) in pentobarbital-anaesthetized normotensive rats, induces a late progressive cognitive decline when compared with sham-operated controls. Analysis at BCCA of hippocampal metabolism using microdialysis showed increased release of glutamate, aspartate and gamma-aminobutyric acid, followed by a progressive rise in the formation of hydroxyl free radicals measured as 2,3-dihydroxybenzoic acid (2,3-DHBA), their reaction product with salicylate, though only in the re-perfusion phase. In the striatum increased dopamine release occurred during BCCA, whereas glutamate and aspartate showed an increase only during the late re-perfusion phase. gamma-Aminobutyric acid (GABA) concentration increased during BCCA and early re-perfusion. An increase in 2,3-DHBA was seen during BCCA, and persisted over 2 h of re-perfusion. Six and 13 months after surgery, though not as early as 3 months, BCCA-treated rats perform worse than sham-operated controls in a water-maze, where decreased swimming speed reveals striatal dysfunction, while hippocampal dysfunction manifested as diminished spatial bias. These results show that cerebral oligaemia, similarly to cerebral ischaemia, leads to increased extracellular dopamine, aspartate and glutamate, and the production of hydroxyl radicals in structures associated with learning and memory processes. Unlike cerebral ischaemia, in cerebral oligaemia the appearance of spatial memory deficits is delayed.


Potentiating KCC2 activity is sufficient to limit the onset and severity of seizures.
The type 2 K+/Cl- cotransporter (KCC2) allows neurons to maintain low intracellular levels of Cl-, a prerequisite for efficient synaptic inhibition. Reductions in KCC2 activity are evident in epilepsy; however, whether these deficits directly contribute to the underlying pathophysiology remains controversial. To address this issue, we created knock-in mice in which threonines 906 and 1007 within KCC2 have been mutated to alanines (KCC2-T906A/T1007A), which prevents its phospho-dependent inactivation. The respective mice appeared normal and did not show any overt phenotypes, and basal neuronal excitability was unaffected. KCC2-T906A/T1007A mice exhibited increased basal neuronal Cl- extrusion, without altering total or plasma membrane accumulation of KCC2. Critically, activity-induced deficits in synaptic inhibition were reduced in the mutant mice. Consistent with this, enhanced KCC2 was sufficient to limit chemoconvulsant-induced epileptiform activity. Furthermore, this increase in KCC2 function mitigated induction of aberrant high-frequency activity during seizures, highlighting depolarizing GABA as a key contributor to the pathological neuronal synchronization seen in epilepsy. Thus, our results demonstrate that potentiating KCC2 represents a therapeutic strategy to alleviate seizures.


Histochemical demonstration of copper and copper-associated protein in the canine liver.
Three different histochemical methods for copper detection were compared. Atomic absorption analysis was used to substantiate the tissue stains. There was good correlation between rhodanine staining and rubeanic acid-stained tissue sections. The orcein reaction for copper-associated protein did not consistently correlate with the methods demonstrating copper. Prolonged staining (72 hours) with rubeanic acid more consistently and clearly detected increased copper in canine livers than did staining with rhodanine. Seventy-two hour staining with rubeanic acid is the method of choice for histochemical detection of copper in canine liver.


Differential Effects of Linkers on the Activity of Amphiphilic Tobramycin Antifungals.
As the threat associated with fungal infections continues to rise and the availability of antifungal drugs remains a concern, it becomes obvious that the need to bolster the antifungal armamentarium is urgent. Building from our previous findings of tobramycin (TOB) derivatives with antifungal activity, we further investigate the effects of various linkers on the biological activity of these aminoglycosides. Herein, we analyze how thioether, sulfone, triazole, amide, and ether functionalities affect the antifungal activity of alkylated TOB derivatives against 22 Candida, Cryptococcus, and Aspergillus species. We also evaluate their impact on the hemolysis of murine erythrocytes and the cytotoxicity against mammalian cell lines. While the triazole linker appears to confer optimal activity overall, all of the linkers incorporated into the TOB derivatives resulted in compounds that are very effective against the Cryptococcus neoformans species, with MIC values ranging from 0.48 to 3.9 μg/mL.


Nanostructured 2D Diporphyrin Honeycomb Film: Photoelectrochemistry, Photodegradation, and Antibacterial Activity.
Surface patterns of well-defined nanostructures play important roles in fabrication of optoelectronic devices and applications in catalysis and biology. In this paper, the diporphyrin honeycomb film, composed of titanium dioxide, protoporphyrin IX, and hemin (TiO2/PPIX/Hem), was synthesized using a dewetting technique with the well-defined polystyrene (PS) monolayer as a template. The TiO2/PPIX/Hem honeycomb film exhibited a higher photoelectrochemical response than that of TiO2 or TiO2/PPIX, which implied a high photoelectric conversion efficiency and a synergistic effect between the two kinds of porphyrins. The TiO2/PPIX/Hem honeycomb film was also a good photosensitizer due to its ability to generate singlet oxygen ((1)O2) under irradiation by visible light. This led to the use of diporphyrin TiO2/PPIX/Hem honeycomb film for the photocatalytic inactivation of bacteria. In addition, the photocatalytic activities of other metal-diporphyrin-based honeycomb films, such as TiO2/MnPPIX/Hem, TiO2/CoPPIX/Hem, TiO2/NiPPIX/Hem, TiO2/CuPPIX/Hem, and TiO2/ZnPPIX/Hem, were investigated. The result demonstrated that the photoelectric properties of diporphyrin-based film could be effectively enhanced by further coupling of porphyrin with metal ions. Such enhanced performance of diporphyrin compounds opened a new way for potential applications in various photoelectrochemical devices and medical fields.


A measure of time perspective with the TAT and some issues of reliability.
In an effort to duplicate high interrater reliability coefficients reported in the use of Epley and Ricks' (1963) time orientation scoring system with the Thematic Apperception Test (TAT), two pairs of judges and two different training procedures were employed. Reliability coefficients considerably lower than those quoted by other researchers were found. One method of using the system was to have judges discuss scoring differences during training and at various times during a research project until perfect agreement was reached. When used as an adjunct with periodic assessment' of reliability as judges scored a large number of stories, reliability coefficients within a range acceptable for research purposes were obtained. This procedure is presented with correlational evidence for the presence of the time factor that the scoring system purports to measure.


PAC1hop, null and hip receptors mediate differential signaling through cyclic AMP and calcium leading to splice variant-specific gene induction in neural cells.
Pituitary adenylate cyclase-activating polypeptide (PACAP)-mediated activation of its G protein-coupled receptor PAC1 results in activation of the two G proteins Gs and Gq to alter second messenger generation and gene transcription in the nervous system, important for homeostatic responses to stress and injury. Heterologous expression of the three major splice variants of the rat PAC1 receptor, PAC1hop, null and hip, in neural NG108-15 cells conferred PACAP-mediated intracellular cAMP generation, while elevation of [Ca(2+)](i) occurred only in PAC1hop-, and to a lesser extent in PAC1null-expressing cells. Induction of vasoactive intestinal polypeptide (VIP) and stanniocalcin 1 (STC1), two genes potentially involved in PACAP's homeostatic responses, was examined as a function of the expressed PAC1 variant. VIP induction was greatest in PAC1hop-expressing cells, suggesting that a maximal transcriptional response requires combinatorial signaling through both cAMP and Ca(2+). STC1 induction was similar for all three receptor splice variants and was mimicked by the adenylate cyclase activator forskolin, indicating that cAMP elevation is sufficient to induce STC1. The degree of activation of two different second messenger pathways appears to determine the transcriptional response, suggesting that cellular responses to stressors are fine-tuned through differential receptor isoform expression. Signaling to the VIP gene proceeded through cAMP and protein kinase A (PKA) in these cells, independently of the MAP kinase ERK1/2. STC1 gene induction by PACAP was dependent on cAMP and ERK1/2, independently of PKA. Differential gene induction via different cAMP dependent signaling pathways potentially provides further targets for the design of treatments for stress-associated disorders.


Autoradiographic analysis of adrenergic receptors in the mammalian brain.
Noradrenaline (NA) exerts its physiological and pharmacological effects in the central nervous system by interacting with specific receptor sites which are divided into four subtypes, namely alpha-1, alpha-2, beta-1 and beta-2 adrenoceptors. Alpha-1 and beta-1 receptors are thought to be neuronal and post-synaptic, whereas alpha-2-R are neuronal pre- and postsynaptic and beta-2-R have a non neuronal (glial, vascular) localization. The autoradiographic localization of adrenergic receptors is requisite to a better understanding of adrenergic modulation in the nervous system. It complements analyses of adrenergic fibers and terminals and allows comparisons between afferent transmission and various receptor systems. In addition, receptor autoradiography is a preliminary step towards non invasive, in vivo receptor imaging using positron emission tomography (PET). Classical autoradiographic methods using tritium-labeled ligands are relatively tedious, as they require exposure times of several months. In order to circumvent these difficulties, an autoradiographic procedure was developed for visualization of I-125-labeled ligands. The method is validated by its application to the analysis of neuronal postsynaptic (alpha-1 and beta-1) adrenoceptors, in ferret visual cortex, in the forebrain of normal and reeler mutant mice and in the embryonic mouse brain. Distributions of alpha-1 and beta-1 adrenoceptors are studied using revelation of HEAT and ICYP binding sites, respectively. The cerebral cortex of ferret was chosen because it is widely used in vision research. The density of both alpha-1 and beta-1 adrenoceptors shows laminar heterogeneities. Beta-receptors are most heavily concentrated in cortical layers I, II and III, but very low in layer IV and moderately represented in layers V and VI. In contrast, alpha-1 receptors are more diffusely distributed, although preferentially concentrated in layer IV and, to a lesser extent, in upper cortical laminae. The two adrenoceptors are thus segregated in the radial dimension of the cortex, following distributions which are nearly complementary. These observations suggest that alpha- and beta-adrenoceptors might be associated with different stages and/or modes of information processing in the primary visual area. Adrenoceptor distribution was mapped in normal and reeler mice, in order to correlate receptor patterns with architectonic anomalies known to exist in reeler mutant mice. In normal mice, beta-1-receptors predominate in striatum, cortical layers I to III, hippocampal regio superior and some thalamic nuclei; they are moderately concentrated in cortical layers V and VI and poorly represented in lamina IV.(ABSTRACT TRUNCATED AT 400 WORDS)


Prevalence of obesity, leanness and anorexia nervosa in Japanese boys and girls aged 12-14 years.
Body weight and height of Japanese boys and girls aged 12-14 years were measured to calculate the prevalence of obesity, leanness and anorexia nervosa. In boys, the prevalence of obesity as well as leanness was significantly higher in the areas where population density was lower and among the boys who attended schools with smaller numbers of pupils. In the girls, these findings were similar to the boys. On the other hand, anorexia nervosa was found in girls only more commonly in the areas with higher population density and in the larger schools. These results suggest that higher prevalence of obesity in certain subjects may be associated with increased numbers of leanness but not with anorexia nervosa.


Exemestane: new preparation. No tangible advance in metastatic breast cancer after tamoxifen failure.
(1) The reference second-line hormone treatment for breast cancer in postmenopausal women, after failure of anti-oestrogen therapy, is an aromatase inhibitor such as letrozole. (2) The clinical assessment file on exemestane, a new aromatase inhibitor licensed for this indication, contains no data from clinical trials versus letrozole or anastrozole, the other oral aromatase inhibitors. Data from non comparative trials fail to show whether cross-resistance between aromatase inhibitors exists. (3) In a double-blind trial involving 769 patients in whom tamoxifen had failed, the antitumour effect of exemestane appeared to be equivalent to that of the progestagen megestrol. (4) This trial showed that the adverse effect profile of exemestane was similar to that of other aromatase inhibitors, with mainly vasomotor flushes, nausea, fatigue and sweating. (5) In practice, the arrival of exemestane changes nothing in the hormone therapy of breast cancer in postmenopausal women, which should consist of tamoxifen (an anti-oestrogen) first; followed by the aromatase inhibitor letrozole if tamoxifen fails.


Strands hybridize in postreplicative adenovirus overlap recombination.
We describe a postreplicative mechanism for adenovirus overlap recombination. An adenovirus minichromosome system was used to study overlap recombination driven by adenovirus DNA replication. Crossing-over appeared to occur equally at, but not within, the borders of the overlap between partner molecules. We propose that recombination in the minichromosome system proceeds through an intermediate formed by direct hybridization of complementary sequences on displaced strands generated by adenovirus-specific DNA replication. Some, but not all, heterologous regions in the intermediate are susceptible to mismatch correction. This pathway is intrinsically nonreciprocal and differs significantly from other adenovirus recombinational mechanisms that have been described previously.


The combination of multi-voxel MR spectroscopy with MR imaging improve the diagnostic accuracy for localization of prostate cancer.
We assessed the usefulness of combined multi-voxel magnetic resonance spectroscopy (MRS) and MR imaging (MRI) in the diagnosis of prostate cancer localization. MRS and MRI were performed in 21 patients with prostate cancer. On T2-weighted images, tumor localization was based on low signal intensity in the peripheral zone. At MRS, cancer patterns were diagnosed when the ratio of choline plus creatine to citrate was greater than 0.86. The results were analyzed with reference to pathological confirmation of prostate cancer at bilateral or unilateral lobe. Six out of 11 patients with unilateral positive biopsy specimens were diagnosed as unilateral cancer, and 9 of 10 patients with bilateral positive biopsy specimens were diagnosed as bilateral cancer on MRI. Two of 4 patients with unilateral cancer, who were not detected on MRI alone, were diagnosed as unilateral cancer on combined MRI and MRS. The accuracy of MRI alone was 71.4%, while that of combined MRI and MRS was 81.0%. Combined MRI and MRS improved the diagnostic accuracy for localization of prostate cancer.


Genotype- and experience-dependent susceptibility to depressive-like responses in the forced-swimming test.
The forced-swimming test (FST) is utilized to reproduce passive coping responses to stress that may model a relevant aspect of human depression in rodent species. Animals showing high levels of passive responses to the FST are assumed to model pathologically depressed individuals. We evaluated sensitivity of FST-induced behavioral responses to the interaction between genetic and environmental influences. Behavioral responses to FST were evaluated in naive mice of the C57BL/6 and DBA/2 strains, in mice of both strains pre-exposed to FST 14 days before test, and in FST-experienced animals subsequently exposed to 12 days of stress experience (food restriction). C57BL/6 mice are characterized by high propensity to adopt passive coping responses in the FST. Moreover, stress enhances FST-induced immobility in mice of the C57BL/6 strain but reduces this response in DBA/2 mice. Finally, FST-induced immobility in C57BL/6 mice is reduced by chronic treatment with clinically effective antidepressants. These results support the view that behavioral and neural responses to FST exhibited by C57BL/6 mice can be usefully exploited by pre-clinical research on depression.


Luminescent film: Biofouling investigation of tetraphenylethylene blended polyethersulfone ultrafiltration membrane.
Despite the huge contribution of membrane-based brine and wastewater purification systems in today's life, biofouling still affects sustainability of membrane engineering. Aimed at reducing membrane modules wastage, the need to study biofouling monitoring as one of contributory factors stemmed from the short time between initial attachment and irreversible biofoulant adhesion. Hence, a membrane for monitoring is introduced to determine the right cleaning time by using fluorescent sensing as a non-destructive and scalable approach. The classical solid-state emissive fluorophore, tetraphenylethylene (TPE), was introduced as a sustainable, safe and sensitive fluorescent indicator in order to show the potential of the method, and polyethersulfone (PES) and nonsolvent-induced phase separation method, the most popular material and method, are used to fabricate membrane in industry and academia. Since the employed filler has an aggregation-induced emission (AIE) characteristic, it can track the biofouling throughout the operation. The fabricated membranes have certain characterizations (i.e. morphology assessment, flux, antibiogram, flow cytometry, surface free energy, and protein adsorption) which indicate that hybrid membrane with 5 wt % of TPE has identical biofouling activity compared to neat PES membrane and its optimal luminescence properties make it an appropriate candidate for non-destructive and online biofouling monitoring.


Retinoic acid inducibility of the human PDGF-a gene is mediated by 5'-distal DNA motifs that overlap with basal enhancer and vitamin D response elements.
Retinoic acid (RA) upregulates expression of PDGF ligands and receptors in neonatal rat lung fibroblasts, a process likely to promote maturation of the lung alveolus and possibly microstructures of other organs. A mutational analysis of the gene encoding the PDGF-A ligand has identified a complex retinoic acid response element (RARE) located far upstream of the transcription start site, in a 5'-distal enhanceosome region previously shown to harbor basal and vitamin D-inducible enhancer activity. Maximal RA responsiveness (fourfold) was conferred by nucleotide sequence located between -7064 and -6787, with a variety of deletion and point mutations revealing the importance of at least three nuclear receptor half-sites within the enhancer region (-6851 to -6824), as well as nucleotides located further upstream. Recombinant human retinoic acid receptor/retinoid-X receptor heterodimers bound with high affinity and sequence specificity to multiple regions within the RARE, as demonstrated by electrophoretic mobility shift and DNase I footprinting assays. The addition of RARE activity to previously described functions of the 5'-distal enhanceosome underscores the importance of this region as a key integration point for regulatory control of PDGF-A expression.


First identification of a phosphorylcholine-substituted protein from Caenorhabditis elegans: isolation and characterization of the aspartyl protease ASP-6.
Caenorhabditis elegans is a widely accepted model system for parasitic nematodes, drug screening and developmental studies. Similar to parasitic worms, C. elegans expresses glycosphingolipids and glycoproteins carrying, in part, phosphorylcholine (PCho) substitutions, which might play important roles in nematode development, fertility and, at least in the case of parasites, survival within the host. With the exception of a major secretory/excretory product from Acanthocheilonema viteae (ES-62), no protein carrying this epitope has been studied in detail yet. Here we report on the identification, characterization and localization of the aspartyl protease ASP-6 of C. elegans, which is excreted by the nematode in a PCho-substituted form. Within the worm, most prominent expression of the protein is observed in the intestine, while muscle and epithelial cells express asp-6 to a lesser extent. In animals harboring an ASP-6::GFP fusion protein, diffuse fluorescence throughout the body cavity of adult worms indicates that the chimeric protein is secreted.


A Rare Case of Post-pubertal Pure Yolk-sac Tumour Incidentally Diagnosed after Surgical Intervention for Fournier's Gangrene.
The testicular tumour is the most common solid malignancy in males between the ages of 15 and 35 years. Testicular tumours most commonly present with a painless testicular mass. Fournier's gangrene is necrotising fasciitis of the genital, perineal, and perianal region characterized by the microvascular thrombosis and skin necrosis, and is most commonly seen in elderly males with the comorbid conditions. To the best of our knowledge, there is no published case of testicular tumour presenting as Fournier's gangrene. Herein, we report a case of a young adult male, otherwise healthy, who presented to the emergency room with Fournier's gangrene and was found to have a metastatic post-pubertal pure yolk-sac tumour of the testis which is extremely rare in the adults. Key Words: Fournier's gangrene, Yolk sac tumour, Testicular neoplasm.


Transcriptional activating regions target a cyclin-dependent kinase.
Several yeast activators are phosphorylated by SRB10, a cyclin-dependent kinase associated with the transcriptional machinery. Sites of phosphorylation are found outside the activating region in each case, and the modification has different physiological consequences in different cases. We show here that certain acidic transcriptional activating regions contact SRB10 as assayed both in vivo and in vitro. The interaction evidently positions each activator, as it activates transcription, so that it gets phosphorylated by SRB10, and thus a common mechanism targets disparate substrates to the kinase.


Preparation of Water-in-Oil Nanoemulsions Loaded with Phenolic-Rich Olive Cake Extract Using Response Surface Methodology Approach.
In this study, we aimed to prepare stable water-in-oil (W/O) nanoemulsions loaded with a phenolic-rich aqueous phase from olive cake extract by applying the response surface methodology and using two methods: rotor-stator mixing and ultrasonic homogenization. The optimal nanoemulsion formulation was 7.4% (w/w) of olive cake extract as the dispersed phase, and 11.2% (w/w) of a surfactant mixture of polyglycerol polyricinoleate (97%) and Tween 80 (3%) in Miglyol oil as the continuous phase. Optimum results were obtained by ultrasonication for 15 min at 20% amplitude, yielding W/O nanoemulsion droplets of 104.9 ± 6.7 nm in diameter and with a polydispersity index (PDI) of 0.156 ± 0.085. Furthermore, an optimal nanoemulsion with a droplet size of 105.8 ± 10.3 nm and a PDI of 0.255 ± 0.045 was prepared using a rotor-stator mixer for 10.1 min at 20,000 rpm. High levels of retention of antioxidant activity (90.2%) and phenolics (83.1-87.2%) were reached after 30 days of storage at room temperature. Both W/O nanoemulsions showed good physical stability during this storage period.


Development of a pharmacist collaborative care program for pulmonary arterial hypertension.
Patients with Pulmonary Arterial Hypertension (PAH) require multidisciplinary care. Involving pharmacists in PAH multidisciplinary care teams may enhance patient education and improve medication use. We describe the implementation of a Pharmacist Collaborative Care Program (PCCP) in a PAH referral centre in Grenoble, France. Initiated in 2007, the PCCP program includes a pharmacist intervention whose goals are educational, psychosocial, and technical. During patient interviews, pharmacists make an 'educational diagnosis' and provide a patient-specific education session. Patient skills are evaluated at the end of the session. Pharmacists provide feedback to nurses and physicians through a standardized report form and discussion during medical rounds and PAH group meetings. Pharmacists re-evaluate patients' skills every 3-6 months during multidisciplinary clinical evaluations. The PCCP program for PAH is an established practice in Grenoble and may inform future patient education programs involving pharmacists in France, where legislation has recently been passed to standardize patient education.


Dyadic interracial interactions: a meta-analysis.
This meta-analysis examined over 40 years of research on interracial interactions by exploring 4 types of outcomes: explicit attitudes toward interaction partners, participants' self-reports of their own emotional state, nonverbal or observed behavior, and objective measures of performance. Data were collected from 108 samples (N = 12,463) comparing dyadic interracial and same-race interactions, predominantly featuring Black and White Americans. Effect sizes were small: Participants in same-race dyads tended to express marginally more positive attitudes about their partners (r = .07), reported feeling less negative affect (r = .10), showed more friendly nonverbal behavior (r = .09), and scored higher on performance measures (r = .07) than those in interracial dyads. Effect sizes also showed substantial heterogeneity, and further analyses indicated that intersectional, contextual, and relational factors moderated these outcomes. For example, when members of a dyad were the same sex, differences between interracial and same-race dyads in negative affect were reduced. Structured interactions led to more egalitarian performance outcomes than did free-form interactions, but the effects of interaction structure on nonverbal behavior depended on participant gender. Furthermore, benefits of intergroup contact were apparent: Differences in emotional state across dyadic racial composition disappeared in longer term interactions, and racial minorities, who often have greater experience with intergroup contact, experienced less negative affect in interracial interactions than did majority group members. Finally, there was a significant historical trend toward more egalitarian outcomes across dyadic racial composition for explicit attitudes and for nonverbal behavior; however, participants' emotional responses and performance have remained consistent.


Ten-hour preservation of guinea pig isolated hearts perfused at low flow with air-saturated Lifor solution at 26{degrees}C: comparison to ViaSpan solution.
There is no suitable solution to preserve hearts for longer than 5 h between donor explant and recipient implant. Lifor is a fully artificial preservation medium containing both a nonprotein oxygen and nutrient carrier (nanoparticles) and cellular nutrients, including amino acids and sugars. We proposed that recirculated Lifor solution would satisfactorily preserve guinea pig isolated hearts perfused at low flow with no added O(2) at room temperature for 10 h. Hearts were isolated from 21 guinea pigs and perfused with Krebs-Ringer (KR) solution (97% O(2) and 3% CO(2)) at 37 degrees C. Heart rate, inflow and outflow O(2) tension, coronary flow, left ventricular pressure (LVP), and maximal and minimal rate of change in LVP (dLVP/dt) were measured. After baseline measurements, hearts were perfused with recirculated Lifor or ViaSpan equilibrated with room air at 15% of control flow at 26 degrees C for 10 h. Hearts were then perfused at 100% flow with KR for 2 h at 37 degrees C. A time control (untreated) group was perfused only with KR solution for 15 h. Lifor arrested and protected hearts against diastolic contracture and maintained a low O(2) extraction. Compared with time controls, Lifor led to a higher developed LVP and coronary flow; %O(2) extraction and cardiac efficiency were similar between these two groups. Hearts similarly treated with ViaSpan exhibited diastolic contracture and lower %O(2) extraction during treatment and, upon reperfusion with KR, exhibited continued diastolic contracture, no return of heart rate or contractility, low coronary flow, low %O(2) extraction, and marked infarction. For long-term cardiac protection, a suitable preservation solution recirculated at low flow and room temperature without supplemental O(2) would reduce the support apparatus required for transport. Lifor was far superior to ViaSpan in meeting these requirements.