Energy-integrating-detector multi-energy CT: Implementation and a phantom study.
Multi-energy computed tomography (MECT) has a great potential to enable many novel clinical applications such as simultaneous multi-contrast imaging. The purpose of this study was to implement triple-beam MECT on a traditional energy-integrating-detector (EID) CT platform (EID-MECT). This was accomplished by mounting a z-axis split-filter (0.05 mm Au, 0.6 mm Sn) on Tube A of a dual-source EID CT scanner. With the two split x-ray beams from Tube A and the third beam from Tube B, three beams with different x-ray spectra can be simultaneously acquired. With Tube B operated at 70 or 80 kV and Tube A at 120 or 140 kV, four different triple-beam configurations were calibrated for MECT measurements: 70/Au120/Sn120, 80/Au120/Sn120, 70/Au140/Sn140, and 80/Au140/Sn140 kV. Iodine (I), gadolinium (Gd), bismuth (Bi) samples, and their mixtures were prepared for 2 three-material-decomposition tasks and 1 four-material-decomposition task. For each task, samples were placed in a water phantom and scanned using each of the four triple-beam configurations. For comparison, the same phantom was also scanned using three other dual-energy CT (DECT) or MECT technologies: twin-beam DECT (TB-DECT), dual-source DECT (DS-DECT), and photon-counting-detector CT (PCD-CT), all with optimal x-ray spectrum settings and at equal volume CT dose index (CTDIvol). The phantom for four-material decomposition (I/Gd/Bi/Water imaging) was scanned using the PCD-CT only (140 kV with 25, 50, 75, and 90 keV). Image-based material decomposition was performed to acquire material-specific images, on which the mean basis material concentrations and noise levels were measured and compared across all triple-beam configurations in EID-MECT and various DECT/MECT systems. The optimal triple-beam configuration was task-dependent with 70/Au120/Sn120, 70/Au140/Sn140, and 70/Au120/Sn120 kV for I/Gd/Water, I/Bi/Water, and I/Gd/Bi/Water material decomposition tasks, respectively. At equal radiation dose level, EID-MECT provided comparable or better quantification accuracy in material-specific images for all three material decomposition tasks, compared to EID-based DECT and PCD-CT systems. In terms of noise level comparison, EID-MECT-derived material-specific images showed lower noise levels than TB-DECT and DS-DECT, but slightly higher than that from PCD-CT in I/Gd/Water imaging. For I/Bi/Water imaging, EID-MECT showed a comparable noise level to DS-DECT, and a much lower noise level than TB-DECT and PCD-CT in all material-specific images. For the four-material decomposition task involving I/Gd/Bi/Water, the bismuth-specific image derived from EID-MECT was slightly noisier, but both iodine- and gadolinium-specific images showed much lower noise levels in comparison to PCD-CT. For the first time, an EID-based MECT system that can simultaneously acquire three x-ray spectra measurements was implemented on a clinical scanner, which demonstrated comparable or better imaging performance than existing DECT and MECT systems.


[The respiratory center--the regulator of the respiratory system].
The authors consider the respiratory centre to be the regulator of the respiratory system and to consist of 3 main functional blocks: chemoregulator, respiratory rhythm autogenerator and mechanoregulator, functions of which are provided by the neurons of medulla oblongata. The main aim of chemoregulator block is to maintain the level of ventilation volume speed, which is necessary to compensate the difference between the signals of setting and the firing from the chemoreceptors. The main aim of mechanoregulator block is to provide the functioning of the regulation loop of the respiratory muscles comparing the signals which come from the respiratory autogenerator, and the firing of the mechanoreceptors. The generator unit of the respiratory centre is a set of rhythm-forming associations, the system of 4 neurons (early and late inspiratory and expiratory) are typical among them. The neurons are connected by recurrent inhibitory bonds: the neuron of each rhythm-forming group, successively becoming excited, inhibits the two preceding neurons in the cycle; for all this the neuron of the successive group is released from inhibition and in such a way the rhythmogenesis occurs. The respiratory centre forms a common unit for chemo- and mechanoreceptor loops, through which the circuits of feedback for both loops are connected, providing the regulation of breathing.


Regulation of the Arabidopsis anther transcriptome by DYT1 for pollen development.
Several genes encoding transcription factors have been shown to be essential for male fertility in plants, suggesting that transcriptional regulation is a major mechanism controlling anther development in Arabidopsis. DYSFUNCTIONAL TAPETUM 1 (DYT1), a putative bHLH transcription factor, plays a critical role in regulating tapetum function and pollen development. Here, we compare the transcriptomes of young anthers of wild-type and the dyt1 mutant, demonstrating that DYT1 is upstream of at least 22 genes encoding transcription factors and regulates the expression of a large number of genes, including genes involved in specific metabolic pathways. We also show that DYT1 can bind to DNA in a sequence-specific manner in vitro, and induction of DYT1 activity in vivo activated the expression of the downstream transcription factor genes MYB35 and MS1. We generated DYT1-SRDX transgenic plants whose fertility was dramatically reduced, implying that DYT1 probably acts as a transcriptional activator. Furthermore, we used yeast two-hybrid assays to show that DYT1 forms homodimers and heterodimers with other bHLH transcription factors. Our results demonstrate the important role of DYT1 in regulating anther transcriptome and function, and supporting normal pollen development.


Mortality risk associated with psychological distress and major depression: A population-based cohort study.
Few studies have examined the impact of psychological distress on mortality. We aimed to estimate mortality rates of psychological distress and major depressive disorder (MDD) compared to a referent group with no MDD or psychological distress. Our study population (N = 10 181) consisted of respondents from the Canadian Community Health Survey Cycle 1.2 linked to Ontario health administrative databases followed for up to 11 years. We used Cox proportional hazards models to assess overall, sex-specific, as well as short-term (within two years of follow-up) and long-term (follow-up ≥ two years) mortality among those with DSM-criteria MDD and psychological distress independent of MDD adjusted for socio-demographic, lifestyle and clinical factors. Individuals with psychological distress (n = 666) had a similar mortality rate as those with MDD (n = 428) and significantly greater adjusted hazards of death than the referent group (hazard ratio = 1.57, 95% CI = 1.14-2.15). The risk of death was greatest in the short-term among those with MDD, however, we observed a persistent 1.6-fold increased risk in both the short- and long-term among those with psychological distress compared to the referent. Women with MDD had the greatest mortality rate and died a median of 15 years earlier than women in the referent group. Psychological distress and MDD were ascertained at baseline with small number of deaths in the early follow-up period. Survey variables were prone to self-report bias with a possibility of residual confounding. Focused longitudinal research and targeted management strategies for those with psychological distress and women with MDD are warranted.


Development of the orohypopharyngeal cavity in normal infants and young children.
To study the growth of the oropharynx and hypopharynx in infants and young children by measuring the lengths of the segments between nasopharyngeal valve and tongue base, tongue base and arytenoids, and arytenoids and upper esophageal sphincter. These measurements will be used as references for developing manofluoroscopy to study deglutition in infants and young children. Twenty-three children (14 boys, 9 girls) between birth and 4 years of age were prospectively studied. All children had near normal growth parameters and were free of medical illnesses or other major medical conditions that are known to influence the pharyngeal cavity. Lateral videofluoroscopy was used to assess the pharyngeal structures during breathing. All images were digitally recorded and analyzed using a computer program designed specifically for this study. Statistically significant correlations were found between the age or height of the patient and the distance from velopharyngeal valve to tongue base and the distance from tongue base to arytenoids, showing a linear increase of the length of the oro- and hypopharynx with age and patient height. There was no significant difference in the pharyngeal distances between boys and girls. On the basis of these results, a linear regression comparison could be established to define the length of each pharyngeal segment for any age until 4 years and for the 50th percentile of height.


MicroRNA-216b regulated proliferation and invasion of non-small cell lung cancer by targeting SOX9.
Micro (mi)RNAs are small, evolutionarily conserved and endogenous noncoding RNA molecules between 19 and 24 nucleotides in length. The potential roles of miRNAs in the carcinogenesis and progression of non-small cell lung cancer (NSCLC) have been studied previously. In the present study, it was revealed that miRNA-216b (miR-216b) expression was lower in NSCLC tissue and cell lines compared with that in adjacent healthy lung tissue samples and the normal bronchial epithelial 16HBE cell line, respectively. The ectopic expression of miR-216b inhibited the proliferation and invasion of NSCLC cells in vitro. SRY-Box 9 (SOX9) was identified as a direct target of miR-216b in NSCLC. In addition, SOX9 small interfering RNA was able to mimic the effects of miR-216b overexpression on cell proliferation and invasion in NSCLC. Therefore, the data reported in the present study demonstrate that miR-216b is an important tumor suppressor in NSCLC. These data may contribute to the understanding of the molecular mechanism underlying the carcinogenesis and progression of NSCLC, and provide novel therapies for patients with NSCLC.


AAV-mediated transduction and targeting of retinal bipolar cells with improved mGluR6 promoters in rodents and primates.
Adeno-associated virus (AAV) vectors have been a powerful gene delivery vehicle to the retina for basic research and gene therapy. For many of these applications, achieving cell type-specific targeting and high transduction efficiency is desired. Recently, there has been increasing interest in AAV-mediated gene targeting to specific retinal bipolar cell types. A 200-bp enhancer in combination with a basal SV40 promoter has been commonly used to target transgenes into ON-type bipolar cells. In the current study, we searched for additional cis-regulatory elements in the mGluR6 gene for improving AAV-mediated transduction efficiency into retinal bipolar cells. Our results showed that the combination of the endogenous mGluR6 promoter with additional enhancers in the introns of the mGluR6 gene markedly enhanced AAV transduction efficiency as well as made the targeting more selective for rod bipolar cells in mice. Furthermore, the AAV vectors with the improved promoter could target to ON bipolar cells with robust transduction efficiency in the parafovea and the far peripheral retina of marmoset monkeys. The improved mGluR6 promoter constructs could provide a valuable tool for genetic manipulation in rod bipolar cells in mice and facilitate clinical applications for ON bipolar cell-based gene therapies.


SEAI: Social Emotional Artificial Intelligence Based on Damasio's Theory of Mind.
A socially intelligent robot must be capable to extract meaningful information in real time from the social environment and react accordingly with coherent human-like behavior. Moreover, it should be able to internalize this information, to reason on it at a higher level, build its own opinions independently, and then automatically bias the decision-making according to its unique experience. In the last decades, neuroscience research highlighted the link between the evolution of such complex behavior and the evolution of a certain level of consciousness, which cannot leave out of a body that feels emotions as discriminants and prompters. In order to develop cognitive systems for social robotics with greater human-likeliness, we used an "understanding by building" approach to model and implement a well-known theory of mind in the form of an artificial intelligence, and we tested it on a sophisticated robotic platform. The name of the presented system is SEAI (Social Emotional Artificial Intelligence), a cognitive system specifically conceived for social and emotional robots. It is designed as a bio-inspired, highly modular, hybrid system with emotion modeling and high-level reasoning capabilities. It follows the deliberative/reactive paradigm where a knowledge-based expert system is aimed at dealing with the high-level symbolic reasoning, while a more conventional reactive paradigm is deputed to the low-level processing and control. The SEAI system is also enriched by a model that simulates the Damasio's theory of consciousness and the theory of Somatic Markers. After a review of similar bio-inspired cognitive systems, we present the scientific foundations and their computational formalization at the basis of the SEAI framework. Then, a deeper technical description of the architecture is disclosed underlining the numerous parallelisms with the human cognitive system. Finally, the influence of artificial emotions and feelings, and their link with the robot's beliefs and decisions have been tested in a physical humanoid involved in Human-Robot Interaction (HRI).


Complementary therapy for addiction: "drumming out drugs".
This article examines drumming activities as complementary addiction treatments and discusses their reported effects. I observed drumming circles for substance abuse (as a participant), interviewed counselors and Internet mailing list participants, initiated a pilot program, and reviewed literature on the effects of drumming. Research reviews indicate that drumming enhances recovery through inducing relaxation and enhancing theta-wave production and brain-wave synchronization. Drumming produces pleasurable experiences, enhanced awareness of preconscious dynamics, release of emotional trauma, and reintegration of self. Drumming alleviates self-centeredness, isolation, and alienation, creating a sense of connectedness with self and others. Drumming provides a secular approach to accessing a higher power and applying spiritual perspectives. Drumming circles have applications as complementary addiction therapy, particularly for repeated relapse and when other counseling modalities have failed.


Mothers of infants with congenital heart defects: well-being from pregnancy through the child's first six months.
This study compared the well-being among mothers of children with congenital heart defects (CHD) with mothers of children without CHD (controls), at pregnancy and at 6 months postpartum. We linked prospective data from the Norwegian Mother and Child Cohort Study (MoBa), conducted by the Norwegian Institute of Public Health, with a nationwide medical CHD registry. In the MoBa cohort of 61,456 mothers, we identified 212 mothers of infants with mild (n = 92), moderate (n = 50), or severe CHD (n = 70). Subjective well-being was operationalized by means of maternal life satisfaction, joy, and anger at the 30th week of gestation and at 6 months postpartum. Subjective well-being in mothers of children with CHD remained unchanged and similar to that of controls on satisfaction with life (P = 0.120) and feelings of joy (P = 0.065). However, at child age 6 months, mothers of infants with severe CHD reported slightly elevated feelings of anger compared with controls (P = 0.006). Joy and life satisfaction remained intact among mothers of children with CHD. Yet, elevated feelings of anger in mothers of children with the most severe CHD suggest that they may experience more frustration.


Perceptions of childhood obesity on the Texas-Mexico border.
We sought to determine the extent of intracultural consensus in perceptions of childhood obesity among Mexican American mothers living on the Texas-Mexico border. A descriptive, cross-sectional study examined women's judgments about the parameters of childhood obesity. The convenience sample consisted of 61 Mexican American women who were mothers of at least 1 child under age 18. Participants underwent an anthropometric assessment and were surveyed regarding self-perceived weight and household food security. They were then shown photographs of 36 Mexican American boys ages 6 and 7 and asked to sort them into categories by weight status; they also selected 3 children they believed represented the healthiest, most appropriate weight for age. Accuracy scores were computed and examined for bivariate relationships with women's own body mass index (BMI) and survey responses. We found considerable intracultural variation in women's judgments, which could not be explained by the anthropometric and survey variables tested. Women selected a wide range of percentiles as representative of a healthy child. On average, about half of the truly overweight children (BMI>or=95th percentile), however, were considered normal or even underweight. Local perceptions and language may not correspond to CDC/WHO clinical standards. Larger studies are needed to confirm these preliminary findings.


Permeability of cortical bone of canine tibiae.
Movement of interstitial fluid in cortical bone is considered one of the important mechanisms affecting bone remodeling and fracture healing. To better understand such interstitial fluid movement, the hydrostatic permeability of cortical bone of the canine tibia was measured in this study. It was found that age has significant influence on permeability. The cortical bone permeability of puppy tibiae is six times higher than that of adult tibiae. Adult tibial cortex is impermeable unless the superficial layer of the periosteal cortex is removed. The permeability differs between regions and locations of the tibia. The pathways for such extravascular interstitial fluid movement were also identified to be primarily the haversian and Volkmann's canals and secondarily the canalicular and lacunar spaces. The high permeability of their cortical bone may explain the increase in periosteal new bone formation seen in puppies when a venous tourniquet is applied.


Utilization of n-alkanes by Pullularia pullulans.
Pullularia pullulans was tested for its ability to utilize a series of n-alkanes for growth. It utilized hydrocarbons containing higher C-numbers (13, 14, 16, and 18) to a greater degree than those containing lower numbers; in addition, an induction phenomenon was noted. Gas-liquid and thin-layer chromatography of ether extracts of the growth media revealed that oleic and palmitic acids were formed from tridecane, tetradecane, hexadecane, and octadecane.


Lymphocyte adherence in multiple sclerosis: effect of aspirin.
Peripheral blood lymphocytes from multiple sclerosis (MS) patients form substantially greater numbers of rosettes with measles virus-infected human epithelial cells than do lymphocytes from healthy controls or from patients with other diseases. We have previously shown that prostaglandin E(1)-treated normal lymphocytes exhibit increased lymphocyte adherence, and thus behave like MS lymphocytes in this in vitro system. In this study we describe the effect of prostaglandin synthesis inhibition on lymphocyte adherence in both MS and control patients. Direct addition of aspirin or indomethacin to peripheral blood mononuclear cells from MS patients in vitro reduced lymphocyte adherence to control levels. Ingestion of therapeutic (anti-inflammatory) doses of aspirin (1 g, 4 times daily for 2 d) by MS patients resulted in reduction of lymphocyte adherence to levels seen in healthy controls. A single 325-mg dose of aspirin did not reduce lymphocyte adherence. A dose-dependent reduction in lymphocyte adherence was observed after single doses ranging from 650 mg to 1.3 g; duration of the effect was directly related to the aspirin dose. These observations indicate that treatment of MS patients with aspirin profoundly influences adherence of their lymphocytes to measles virus-infected cells and suggest that the altered cellular response, which results in increased lymphocyte adherence in MS patients, may be mediated by a prostaglandin-sensitive mechanism.


Prenatal Diagnosis and Evaluation of Abnormal Placentation.
Abnormalities in placental location or adherence can have important consequences on pregnancy outcome for both mother and fetus. Accurate antenatal detection is crucial for delivery timing and planning to help reduce perinatal risks for adverse events. We review the relevant literature and present a practical approach for the prenatal detection of abnormal placentation.


Curation-free biomodules mechanisms in prostate cancer predict recurrent disease.
Gene expression-based prostate cancer gene signatures of poor prognosis are hampered by lack of gene feature reproducibility and a lack of understandability of their function. Molecular pathway-level mechanisms are intrinsically more stable and more robust than an individual gene. The Functional Analysis of Individual Microarray Expression (FAIME) we developed allows distinctive sample-level pathway measurements with utility for correlation with continuous phenotypes (e.g. survival). Further, we and others have previously demonstrated that pathway-level classifiers can be as accurate as gene-level classifiers using curated genesets that may implicitly comprise ascertainment biases (e.g. KEGG, GO). Here, we hypothesized that transformation of individual prostate cancer patient gene expression to pathway-level mechanisms derived from automated high throughput analyses of genomic datasets may also permit personalized pathway analysis and improve prognosis of recurrent disease. Via FAIME, three independent prostate gene expression arrays with both normal and tumor samples were transformed into two distinct types of molecular pathway mechanisms: (i) the curated Gene Ontology (GO) and (ii) dynamic expression activity networks of cancer (Cancer Modules). FAIME-derived mechanisms for tumorigenesis were then identified and compared. Curated GO and computationally generated "Cancer Module" mechanisms overlap significantly and are enriched for known oncogenic deregulations and highlight potential areas of investigation. We further show in two independent datasets that these pathway-level tumorigenesis mechanisms can identify men who are more likely to develop recurrent prostate cancer (log-rank_p = 0.019). Curation-free biomodules classification derived from congruent gene expression activation breaks from the paradigm of recapitulating the known curated pathway mechanism universe.


The cost-effectiveness of growth hormone replacement therapy (Genotropin®) in hypopituitary adults in Sweden.
To evaluate the cost-effectiveness of growth hormone (GH) treatment (Genotropin®) compared with no GH treatment in adults with GH deficiency in a Swedish societal setting. A Markov-type cost-utility simulation model was constructed and used to simulate, for men and women, morbidity and mortality for GH-treated and -untreated individuals over a 20-year period. The calculations were performed using current available prices concerning morbidity-related healthcare costs and costs for Genotropin®. All costs and treatment effects were discounted at 3%. Costs were expressed in Euro (1€ = 9.03 SEK). GH-treated Swedish patients (n = 434) were identified from the KIMS database (Pfizer International Metabolic Database) and untreated patients (n = 2135) from the Swedish Cancer Registry and the Hospital Discharge Registry. The results are reported as incremental cost per quality-adjusted life year (QALY) gained, including both direct and indirect costs for GH-treated versus untreated patients. The weighted sum of all subgroup incremental cost per QALY was €15,975 and €20,241 for men and women, respectively. Including indirect cost resulted in lower cost per QALY gained: €11,173 and €10,753 for men and women, respectively. Key drivers of the results were improvement in quality of life, increased survival, and intervention cost. The incremental cost per QALY gained is moderate when compared with informal thresholds applied in Sweden. The simulations suggest that GH-treatment is cost-effective for both men and women at the €55,371 (SEK 500,000 - the informal Swedish cost-effectiveness threshold) per QALY threshold.


Ratio of diastolic to systolic blood pressure represents renal resistive index.
Increased intrarenal vascular resistance is suggested to accompany chronic kidney diseases (CKD), which is known to be closely associated with hypertension. However, there are few studies that have examined the relationship between blood pressure and intrarenal vascular resistance. Renal color Doppler ultrasonography is one method that can non-invasively evaluate intrarenal vascular resistance. In this study, we comprehensively studied the correlations between ultrasonic parameters and blood pressure indices to elucidate their relationships. In total, 162 patients with suspected CKD were enrolled for this study. Demographics, blood pressure, blood test, urine test, and renal color Doppler ultrasonography data were obtained. The ratio of diastolic to systolic blood pressure (D/S ratio) and pulse pressure were calculated. Our results indicated strong negative correlations between the renal resistive index (RI) values in all four of the studied kidney regions and the D/S ratio. The RI values also showed significant correlations with diastolic pressure and pulse pressure, but they were weaker. Partial correlation coefficients between pulse pressure, mean arterial pressure, D/S ratio, and RI showed that D/S ratio significantly correlated with RI, but pulse pressure or mean arterial pressure did not. Systolic blood pressure did not correlate with any of the studied ultrasonic values. The negative correlation between RI values and the D/S ratio was still observed in subjects without renal dysfunction or any medications. In conclusion, D/S ratio, rather than pulse pressure or mean arterial pressure, would be the most appropriate index to estimate/calculate/judge intrarenal vascular resistance.


Processing of glycoproteins induced by herpes simplex virus type 1: sulphation and nature of the oligosaccharide linkages.
Using the drug tunicamycin we have investigated the nature of the oligosaccharides on herpes simplex virus type 1 (HSV-1)-induced glycoproteins E and Y (gY is a newly identified glycoprotein which has the same apparent mol. wt. as gC but a more basic isoelectric point). Synthesis of both glycoproteins was inhibited by the drug, suggesting they contain N-linked oligosaccharides. Our finding, combined with the previous results of other workers, suggests that all the major HSV-induced glycoproteins have this type of carbohydrate modification. All of the major HSV-1-induced glycoproteins are modified by addition of inorganic sulphate. This modification occurs late in their maturation. Most inorganic sulphate appears to be attached to N-linked oligosaccharides but some is attached to other parts of glycoprotein E. Using HSV-1/HSV-2 intertypic recombinants, the mapping limits of that part of the glycoprotein E gene coding for differences in mobility between the two serotypes have been further narrowed and are located between coordinates 0.886 and 0.935.


Keeping education fresh-not just in microbiology.
Innovative practice from around the globe, addressing a range of recent educational themes and trends, was published in the FEMS Microbiology Letters virtual Thematic Issue 'Keeping Education Fresh' in October 2017. Its thought-provoking content is reviewed here to more directly facilitate reflections and discussions in the professional community. The focus is on best practice approaches when enhancing student engagement, how to adjust those to the diversity of learners, learning situations and infrastructures, and to a broad range of subjects. The need for authentic learning and to move away from didactic teaching is emphasized. The 'students as researchers' theme is featured e.g. in context of service learning. Creative approaches are presented such as using performing arts, popular culture and gamification. The development of interdisciplinary and intercultural competences, and the exploration of socioscientific themes and philosophical issues are considered. Revisions of curricula and programmes, reflective of educational advancements and sector drivers, are discussed from undergraduate to postgraduate and professional specialist level also in light of problem-based learning, interactive distance and on-campus learning, and even the legacy of Massive Open Online Courses. Such changes always require resources and skills, and carry risks. Yet, innovation is a risk worth taking to keep education fresh.


Marked decline in forest-dependent small mammals following habitat loss and fragmentation in an Amazonian deforestation frontier.
Agricultural frontier expansion into the Amazon over the last four decades has created million hectares of fragmented forests. While many species undergo local extinctions within remaining forest patches, this may be compensated by native species from neighbouring open-habitat areas potentially invading these patches, particularly as forest habitats become increasingly degraded. Here, we examine the effects of habitat loss, fragmentation and degradation on small mammal assemblages in a southern Amazonian deforestation frontier, while accounting for species-specific degree of forest-dependency. We surveyed small mammals at three continuous forest sites and 19 forest patches of different sizes and degrees of isolation. We further sampled matrix habitats adjacent to forest patches, which allowed us to classify each species according to forest-dependency and generate a community-averaged forest-dependency index for each site. Based on 21,568 trap-nights, we recorded 970 small mammals representing 20 species: 12 forest-dependents, 5 matrix-tolerants and 3 open-habitat specialists. Across the gradient of forest patch size, small mammal assemblages failed to show the typical species-area relationship, but this relationship held true when either species abundance or composition was considered. Species composition was further mediated by community-averaged forest-dependency, so that smaller forest patches were occupied by a lower proportion of forest-dependent rodents and marsupials. Both species richness and abundance increased in less isolated fragments surrounded by structurally simplified matrix habitats (e.g. active or abandoned cattle pastures). While shorter distances between forest patches may favour small mammal abundances, forest area and matrix complexity dictated which species could persist within forest fragments according to their degree of forest-dependency. Small mammal local extinctions in small forest patches within Amazonian deforestation frontiers are therefore likely offset by the incursion of open-habitat species. To preclude the dominance of those species, and consequent losses of native species and associated ecosystem functions, management actions should limit or reduce areas dedicated to pasture, additionally maintaining more structurally complex matrix habitats across fragmented landscapes.


Measurement of facial soft tissue mobility in man.
The assessment of facial mobility is a key element in the treatment of patients with facial motor deficits. In this study, we explored the utility of a three-dimensional tracking system in the measurement of facial movements. First, the three-dimensional movement of potentially stable facial soft-tissue, headcap, and dental landmarks was measured with respect to a fixed space frame. Based on the assumption that the dental landmarks are stable, their motion during a series of standardized facial animations was subtracted from that of the facial and headcap landmarks to estimate their movement within the face. This residual movement was used to determine which points are relatively stable (< or = 1.5 mm of movement) and which are not (> or = 1.5 mm of movement). Headcap landmarks were found to be suitable as references during smile, cheek puff, and lip purse animations, and during talking. In contrast, skin-based landmarks were unsuitable as references because of their considerable and highly variable movement during facial animation. Second, the facial movements of patients with obvious facial deformities were compared with those of matched controls to characterize the face validity of three-dimensional tracking. In all instances, pictures that appear to be characteristic of the various functional deficits emerged. Our results argue that tracking instrumentation is a potentially useful tool in the measurement of facial mobility.


Ethics of health research with prisoners in Canada.
Despite the growing recognition for the need to improve the health of prisoners in Canada and the need for health research, there has been little discussion of the ethical issues with regards to health research with prisoners in Canada. The purpose of this paper is to encourage a national conversation about what it means to conduct ethically sound health research with prisoners given the current realities of the Canadian system. Lessons from the Canadian system could presumably apply in other jurisdictions. Any discussion regarding research ethics with Canadian prisoners must begin by first taking into account the disproportionate number of Indigenous prisoners (e.g., 22-25% of prisoners are Indigenous, while representing approximately 3% of the general Canadian population) and the high proportion of prisoners suffering from mental illnesses (e.g., 45% of males and 69% of female inmates required mental health interventions while in custody). The main ethical challenges that researchers must navigate are (a) the power imbalances between them, the correctional services staff, and the prisoners, and the effects this has on obtaining voluntary consent to research; and (b), the various challenges associated to protecting the privacy and confidentiality of study participants who are prisoners. In order to solve these challenges, a first step would be to develop clear and transparent processes for ethical health research, which ought to be informed by multiple stakeholders, including prisoners, the correctional services staff, and researchers themselves. Stakeholder and community engagement ought to occur in Canada with regards to ethical health research with prisoners that should also include consultation with various parties, including prisoners, correctional services staff, and researchers. It is important that national and provincial research ethics organizations examine the sufficiency of existing research ethics guidance and, where there are gaps, to develop guidelines and help craft policy.


Aggression, academic behaviors, and popularity perceptions among boys of color during the transition to middle school.
The transition to middle school often presents behavioral and academic challenges to youths. Boys of color (i.e., African American and Hispanic in this study) may be especially vulnerable. In this study, peer nominations of aggressive and academic behaviors as well as youths' perceptions of how these behaviors were related to popularity in peer networks were obtained from the spring semester of fifth grade through the spring semester of seventh grade, with the transition occurring as the students entered the sixth grade. The sample included 188 boys (71 Caucasian, 90 African American, and 27 Hispanic) from an urban school district in the northeastern United States. Trajectory analyses showed that African American boys scored lower in studentship and higher in rule-breaking and aggressive (both physical and social) behaviors prior to the transition, and such differences among ethnic groups were largely maintained during the transition. Hispanic boys displayed decreases in their studentship during the transition. African American boys' perception of how studentship affects popularity was more positive than other boys prior to the transition, but it decreased during the transition. African American boys also endorsed rule breaking and physical and social aggression more positively for popularity prior to the transition, whereas Caucasian and Hispanic boys' endorsement increased during the transition and eventually caught up with those of African American boys in seventh grade. A positive within-individual association was found between youths' popularity perception and their behavior for studentship, rule breaking, and physical aggression, which did not differ by ethnicity.


Impact of new allocation system on length of stay following heart transplantation in the United States.
United Network for Organ Sharing (UNOS) allocation criteria changed in 2018 to accommodate the increased prevalence of ventricular assist device use as a bridge to heart transplant, which consequently prioritized sicker patients. We aimed to assess the impact of this new allocation policy on the length of stay following heart transplantation. Secondary outcomes include other risk factors for prolonged hospitalization and its effect on mortality and postoperative complications. The UNOS Registry was queried to identify patients who underwent isolated heart transplants in the United States between 2001 and 2023. Patients were divided into quartiles according to their respective length of stay. A total of 57 020 patients were included, 15 357 of which were allocated with the new system. The median hospital length of stay was 15 days (mean 22.7 days). Length of stay was longer in the new allocation era (25 ± 30 vs. 22 ± 27 days, p < .001). The longer length of stay was associated with increased 5-year mortality in the new allocation system (aHR: 1.18; 95% CI: 1.15, 1.20; p-value: < .001). Longer hospital stays and associated observed increased risk for mortality in the era after the allocation criteria change reflect the rationale of this shift which was to prioritize heart transplants for sicker patients. Further studies are needed to track the progress of surgical and perioperative management of these studies over time.


Modified Basket Suture of a Floppy or Irregular Iris in Endothelial Keratoplasty.
Performing endothelial keratoplasty in an eye with a damaged or irregular iris can result in uneven air filling, air escape behind the pupil, anterior iris curvature, a shallow anterior chamber, an uneven anterior chamber depth, difficulty inserting and opening the graft, and iris trauma. We herein present a modified basket suture technique to prevent these iris complications. Before insertion of the corneal donor graft, a double-armed 9-0 polypropylene suture on a curved needle is inserted from 4 equidistant points at the corneal limbus to create a box configuration directly anterior to the iris. These sutures prevent the iris from moving toward the cornea and the anterior chamber from becoming shallow when air replacement is performed. The suture also reduces intraoperative or postoperative iris-related problems because the air filling is more uniform and less prone to migration.


GUTI: a new antigen in the Cromer blood group system.
The Cromer blood group system consists of seven high-incidence and three low-incidence antigens carried on decay-accelerating factor (DAF). This report describes the identification and characterization of a new Cromer high-incidence antigen, named GUTI. RT-PCR and sequence analysis were performed on cDNA prepared from a Chilean donor whose serum contained the alloantibody (anti-GUTI). Based on the observed point mutation, a PCR-RFLP assay using MaeII was developed. To map the epitope, DAF-deletion mutants were tested by immunoblotting with anti-GUTI. Sequence analysis revealed a substitution of 719G>A in DAF in the proband. The proband's parents and two daughters were heterozygotes for 719G>A, one sister whose RBCs typed GUTI- was homozygous for 719A, and one sister had the wild-type DAF (719G). Seven additional heterozygote samples were identified among 214 Chileans. No heterozygotes were found in 197 New York donors. Analysis using DAF-deletion mutants showed the antigenic determinant to be within short consensus repeat (SCR) 4. This study describes a novel high- incidence antigen (GUTI) in the Cromer blood group system characterized by the amino acid arginine at position 206 in SCR4 of DAF. The GUTI-negative proband has a substitution mutation that predicts for histidine at this position.


Magnetic Resonance Imaging and Arthroscopic Correlation in Shoulder Instability.
The shoulder is the most inherently unstable joint in the body, prone to high rates of anterior dislocations with subsequent injuries to soft tissue and bony stabilizing structures, resulting in recurrent shoulder instability. Advanced imaging utilizing magnetic resonance (MR) imaging and MR arthrography allows for thorough evaluation of lesions present in the unstable shoulder and is critical for preoperative planning. Arthroscopic shoulder stabilization in the appropriately selected patient can help restore stability and function. This review highlights correlations between MR imaging and arthroscopy of the most commonly reported soft tissue and bony injuries present in patients with shoulder instability.


Beryllium toxicity. The selective inhibition of casein kinase 1.
1. Cyclic AMP-independent casein kinase 1 in liver cytoplasm and nuclei was inhibited by Be2+ in vitro (Ki 2.5 microM and 29 microM respectively). Casein kinase 2 (phosvitin kinase) and cyclic AMP-dependent protein kinase were unaffected. 2. The inhibition of casein kinase 1 by Be2+ was competitive with respect to the protein substrate; at non-saturating concentrations of casein, inhibition was non-competitive with respect to ATP. 3. In rats given LD50 doses of Be2+ 24 h before death, the activities of cytoplasmic and nuclear casein kinase 1 in livers from partially hepatectomized animals were diminished approx. 50%; with intact rats, nuclear casein kinase 1 was inhibited at concentrations of casein less than the Km.


Modulation of the Immune System for the Treatment of Glaucoma.
At present intraocular pressure (IOP) lowering therapies are the only approach to treat glaucoma. Neuroprotective strategies to protect the retinal ganglion cells (RGC) from apoptosis are lacking to date. Substantial amount of research concerning the role of the immune system in glaucoma has been performed in the recent years. This review aims to analyse changes found in the peripheral immune system, as well as selected local changes of retina immune cells in the glaucomatous retina. By dividing the immune system into the innate and the adaptive immune system, a systematic literature research was performed to find recent approaches concerning the modulation of the immune system in the context of glaucoma. Also ClinicalTrials.gov was assessed to identify studies with a translational context. We found that some aspects of the immune system, such as changes in antibody levels, changes in toll like receptor signalling, T cells and retinal microglial cells, experience more research activity than other areas such as changes in dendritic cells or macrophages. Briefly, results from clinical studies revealed altered immunoreactivities against retinal and optic nerve antigens in sera and aqueous humor of glaucoma patients and point toward an autoimmune involvement in glaucomatous neurodegeneration and RGC death. IgG accumulations along with plasma cells were found localised in human glaucomatous retinae in a pro-inflammatory environment possibly maintained by microglia. Animal studies show that antibodies (e.g. anti- heat shock protein 60 and anti-myelin basic protein) elevated in glaucoma patients provoke autoaggressive RGC loss and are associated with IgG depositions and increased microglial cells. Also, studies addressing changes in T lymphocytes, macrophages but also local immune responses in the retina have been performed and also hold promising results. This recapitulation of recent literature demonstrates that the immune system definitely plays a role in the pathogenesis of glaucoma. Multiple changes in the peripheral innate as well as adaptive immune system have been detected and give room for further research concerning valuable therapeutic targets. We conclude that there still is a great need to bring together the results derived from basic research analysing different aspects of the immune system in glaucoma to understand the immune context of the disease. Furthermore local immune changes in the retina of glaucoma patients still leave room for further therapeutic targets.


Structural characterization of the GM1 ganglioside by infrared multiphoton dissociation, electron capture dissociation, and electron detachment dissociation electrospray ionization FT-ICR MS/MS.
Gangliosides play important biological roles and structural characterization of both the carbohydrate and the lipid moieties is important. The FT-ICR MS/MS techniques of electron capture dissociation (ECD), electron detachment dissociation (EDD), and infrared multiphoton dissociation (IRMPD) provide extensive fragmentation of the protonated and deprotonated GM1 ganglioside. ECD provides extensive structural information, including identification of both halves of the ceramide and cleavage of the acetyl moiety of the N-acetylated sugars. IRMPD provides similar glycan fragmentation but no cleavage of the acetyl moiety. Cleavage between the fatty acid and the long-chain base of the ceramide moiety is seen in negative-ion IRMPD but not in positive-ion IRMPD of GM1. Furthermore, this extent of fragmentation requires a range of laser powers, whereas all information is available from a single ECD experiment. However, stepwise fragmentation by IRMPD may be used to map the relative labilities for a series of cleavages. EDD provides the alternative of electron-induced fragmentation for negative ions with extensive fragmentation, but suffers from low efficiency as well as complication of data analysis by frequent loss of hydrogen atoms. We also show that analysis of MS/MS data for glycolipids is greatly simplified by classification of product ion masses to specific regions of the ganglioside based solely on mass defect graphical analysis.


A molecular prognostic model predicts esophageal squamous cell carcinoma prognosis.
Esophageal squamous cell carcinoma (ESCC) has the highest mortality rates in China. The 5-year survival rate of ESCC remains dismal despite improvements in treatments such as surgical resection and adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. The aim of the present study, therefore, was to develop an immunohistochemistry-based prognostic model to improve clinical risk assessment for patients with ESCC. We developed a molecular prognostic model based on the combined expression of axis of epidermal growth factor receptor (EGFR), phosphorylated Specificity protein 1 (p-Sp1), and Fascin proteins. The presence of this prognostic model and associated clinical outcomes were analyzed for 130 formalin-fixed, paraffin-embedded esophageal curative resection specimens (generation dataset) and validated using an independent cohort of 185 specimens (validation dataset). The expression of these three genes at the protein level was used to build a molecular prognostic model that was highly predictive of ESCC survival in both generation and validation datasets (P = 0.001). Regression analysis showed that this molecular prognostic model was strongly and independently predictive of overall survival (hazard ratio = 2.358 [95% CI, 1.391-3.996], P = 0.001 in generation dataset; hazard ratio = 1.990 [95% CI, 1.256-3.154], P = 0.003 in validation dataset). Furthermore, the predictive ability of these 3 biomarkers in combination was more robust than that of each individual biomarker. This technically simple immunohistochemistry-based molecular model accurately predicts ESCC patient survival and thus could serve as a complement to current clinical risk stratification approaches.


A novel function of the key nitrogen-fixation activator NifA in beta-rhizobia: Repression of bacterial auxin synthesis during symbiosis.
Rhizobia fix nitrogen within root nodules of host plants where nitrogenase expression is strictly controlled by its key regulator NifA. We recently discovered that in nodules infected by the beta-rhizobial strain Paraburkholderia phymatum STM815, NifA controls expression of two bacterial auxin synthesis genes. Both the iaaM and iaaH transcripts, as well as the metabolites indole-acetamide (IAM) and indole-3-acetic acid (IAA) showed increased abundance in nodules occupied by a nifA mutant compared to wild-type nodules. Here, we document the structural changes that a P. phymatum nifA mutant induces in common bean (Phaseolus vulgaris) nodules, eventually leading to hypernodulation. To investigate the role of the P. phymatum iaaMH genes during symbiosis, we monitored their expression in presence and absence of NifA over different stages of the symbiosis. The iaaMH genes were found to be under negative control of NifA in all symbiotic stages. While a P. phymatum iaaMH mutant produced the same number of nodules and nitrogenase activity as the wild-type strain, the nifA mutant produced more nodules than the wild-type that clustered into regularly-patterned root zones. Mutation of the iaaMH genes in a nifA mutant background reduced the presence of these nodule clusters on the root. We further show that the P. phymatum iaaMH genes are located in a region of the symbiotic plasmid with a significantly lower GC content and exhibit high similarity to two genes of the IAM pathway often used by bacterial phytopathogens to deploy IAA as a virulence factor. Overall, our data suggest that the increased abundance of rhizobial auxin in the non-fixing nifA mutant strain enables greater root infection rates and a role for bacterial auxin production in the control of early stage symbiotic interactions.


Simulation of molecular dynamics of water movement in ion channels.
The motion of water molecules in a gramicidin-like channel was studied by the molecular dynamics method. Water molecules are presented in the ST2 model. The structure of the channel was presented in the form of channel's helix frame possessing mobile dipole groups. The interaction of all mobile particles with the membrane channel's walls was taken into account. The calculation consisted of 50,000 integration steps of delta t = 5 x 10(-16) s which corresponded to a total elapsed time of 25 ps. It was shown that water molecules in the channel did not possess rigid spatial structure but exhibited a structure oriented along the channel axis. The motion of water molecules in the channel occurred smoothly, i.e. all water molecules did not have any deep, stable potential wells in the channel. The distribution of water molecules along the radial coordinate of the channel was estimated. Water density was shown to be maximal near the channel axis.


Associations between PTPRC rs10919563 A/G and FCGR2A R131H polymorphisms and responsiveness to TNF blockers in rheumatoid arthritis: a meta-analysis.
We aimed to investigate whether the PTPRC rs10919563 A/G and Fc gamma receptor 2A (FCGR2A) R131H polymorphisms can predict the response to anti-TNF therapy in rheumatoid arthritis (RA) patients. We conducted a meta-analysis of studies on the association between the PTPRC rs10919563 A/G or the FCGR2A R131H polymorphism and responsiveness to anti-TNF therapy in RA patients. Eighteen studies (twelve on PTPRC and six on FCGR2A) from eight articles involving 3058 patients were considered in this meta-analysis. The meta-analysis showed a significant association between the PTPRC rs10919563 A allele and response to TNF-α blockers in RA. The OR of the PTPRC A allele was significantly lower in responders (OR = 0.584, 95 % CI = 0.409-0.835, P = 0.003). Meta-analysis revealed no association between the FCGR2A HH + HR genotype and responsiveness to TNF blockers in all study subjects (OR = 0.762, 95 % CI = 0.543-1.068, P = 0.115). However, stratification by TNF inhibitor type showed that the FCGR2A HH + HR genotype was associated with responsiveness to adalimumab (OR = 0.591, 95 % CI = 0.369-0.947, P = 0.029), but not infliximab and etanercept (OR = 0.929, 95 % CI = 0.354-2.440, P = 0.881; OR = 0.804, 95 % CI = 0.293-2.207, P = 0.673). The PTPRC rs10919563 A allele shows a poor response to anti-TNF therapy, and the FCGR2A HH + HR genotype shows a poor response to adalimumab for RA. Genotyping for these polymorphisms may be useful for predicting the response to TNF-α blockers with respect to personalized medicine.


Blood Pressure Lowering and Safety Improvements With Liver Angiotensinogen Inhibition in Models of Hypertension and Kidney Injury.
Uncontrolled hypertension is an important contributor to cardiovascular disease. Despite the armamentarium of antihypertensive treatments, there remains a need for novel agents effective in individuals who cannot reach acceptable blood pressure levels. Inhibitors targeting the renin-angiotensin-aldosterone system (RAAS) are widely used but may not optimally inhibit RAAS and demonstrate an acceptable safety profile. Experiments were conducted to characterize a series of AGT (angiotensinogen) antisense oligonucleotides (ASOs) and compare their efficacy and tolerability to traditional RAAS blockade. AGT ASOs which target multiple systemic sites of AGT versus an N-acetylgalactosamine-conjugated AGT ASO that targets the liver were compared with captopril and losartan. Spontaneously hypertensive rats fed an 8% NaCl diet, a model of malignant hypertension resistant to standard RAAS inhibitors, demonstrated robust and durable blood pressure reductions with AGT ASO treatments, which was not observed with standard RAAS blockade. Studies in rat models of acute kidney injury produced by salt deprivation revealed kidney injury with ASO treatment that reduced kidney-expressed AGT, but not in animals treated with the N-acetylgalactosamine AGT ASO despite comparable plasma AGT reductions. Administration of either captopril or losartan also produced acute kidney injury during salt deprivation. Thus, intrarenal RAAS derived from kidney AGT, and inhibited by the standard of care, contributes to the maintenance of renal function during severe RAAS challenge. Such improvements in efficacy and tolerability by a liver-selective AGT inhibitor could be desirable in individuals not at their blood pressure goal with existing RAAS blockade.


[A study of the spinal fluid flow by magnetic resonance imaging].
The study was undertaken to examine the potentialities of new MRI techniques (MR-myelocysternoventriculography and phasic contrast-enhanced MRI with reference to a cardiac cycle) in visualizing the spinal fluid system and flow in different groups of neurosurgical patients. MR-myelocysternoventriculography was based on the sequences of SSFP-3D (Signa, GE, 1.5 T) and PSIF-3D (Magnetom 42SP, Siemens, 1.0 T). These regimens were applied to obtain highly T2*-weighed images. These techniques were used in 280 patients. Phasic contrast-enhanced MRI with reference to a cardiac cycle was performed in the axial (through the aqueduct of the cerebrum) and sagittal projects (CINE-2D mode, Signa GE). This technique was employed to study 30 patients and 5 healthy volunteers. MRI-cysternography based on SSFP-3D- and PSIF-3D sequences is recommended as the method of choice in evaluating the 3rd ventriculostoma and, in combination with spiral computed tomography, in detecting fistulas of the base of the skull. Phasic contrast-enhanced MRI with reference to a cardiac cycle yielded the values of spinal fluid flow through the aqueduct of the cerebrum in health: Vsyst max = 4.1 +/- 1.3 cm/sec; Vsyst mean = 2.5 +/- 1.4 cm/sec; Vdiast max = 3.4 +/- 1.5 cm/sec; Vdist mean = 2.5 +/- 1.7 cm/sec (N = 5). The prospect of the technique is to develop recommendations and to predict prognosis while making bypass surgery for ventriculostomas and cystostomas.


hCXCR1 and hCXCR2 antagonists derived from combinatorial peptide libraries.
The human CXCL8 plays important roles in inflammation by activation of neutrophils through the hCXCR1 and hCXCR2 receptors. The role of hCXCR1 and hCXCR2 in the pathogenesis of inflammatory responses has encouraged the development of antagonists of these receptors. In this study, we used phage display peptide libraries to identify peptides antagonists that block the interactions between hCXCL8 and hCXCR1/2. Two linear hexapeptides (MSRAKE and CAKELR) and two disulfide-constrained hexapeptides (CLRSGRFC and CLPWKENC) were recovered by panning phage libraries on hCXCR1- and hCXCR2-transfected murine pre-B cells after specific elution with hCXCL8. Sequence analysis revealed homology between the linear hexapeptides and the N-terminal domain (1-SAKELR-6), whereas the constrained peptides are composed of non-contiguous amino acids mimicking spatial structure on the surface of folded C-terminal portion of hCXCL8 (50-CLDPKENWVQRVVEKFLKRAENS-72). The synthetic linear and structurally constrained peptides competed for (125)I-hCXCL8 binding to hCXCR1 and hCXCR2 (IC(50) comprised between 10 and 100μM). Furthermore, they inhibited the intracellular calcium flux and the migration of hCXCR1/hCXCR2 transfectants; and desensitized hCXCR1 and hCXCR2 receptors on neutrophils, reducing their chemotactic responses induced by ELR-CXC chemokines (hCXCL8, hCXCL1, hCXCL2, hCXCL3, and hCXCL5). To better characterize the residues required for hCXCL8 binding, we identified three linear peptides MLRQTR, HASILP and KKEPWI specific to hCXCL8. These peptides similarly displaced the binding of (125)I-hCXCL8 to hCXCR1 (IC(50) ranging from 8.5 to 10μM) in a dose-dependent manner, inhibited hCXCL8 induced increases in the intracellular calcium, and migration of hCXCR1- and hCXCR2-transfected cells. The identified peptides could be used as antagonists of hCXCL8-induced activities related to its interaction with hCXCR1 and hCXCR2 receptors and may help in the design of new anti-inflammatory therapeutic molecules.


[Glutamate-binding membrane proteins from human platelets].
Solubilization of the total membrane fraction of human platelets in a 2% solution of sodium deoxycholate and subsequent affinity chromatography on glutamate agarose resulted in two protein fractions possessing a glutamate-binding activity. As can be evidenced from radioligand binding data, the first fraction contains two types of binding sites (Kd1 = 1 microM, Bmax 1 = 100 pmol/mg of protein; Kd2 = 9.3 microMm Bmax2 = 395 pmol/mg of protein). The second fraction has only one type of binding sites (Kd = 1 microM, Bmax = = 110 pmol/mg of protein). SDS-PAAG electrophoresis revealed the presence in the first fraction of proteins with Mr of 14, 24, 56 and 155 kDa, whereas the second fraction was found to contain 14, 46, 71 and 155 kDa proteins. Solid phase immunoenzymatic analysis using poly- and monoclonal specific antibodies against mammalian brain glutamate-binding proteins revealed a marked immunochemical similarity of the isolated protein fractions with human brain synaptic membrane glutamate-binding proteins.


The ethical foundations of a duty to treat HIV-positive patients.
Unfortunately, those who commit the most egregious acts of HIV-related discrimination may not be motivated to change either by fines and sanctions, or by educational programs. Perhaps the best solution to dealing with the small, but significant, number of health care providers who discriminate against HIV-positive patients is the action of the majority. Most dentists are ethical and concerned health care professionals, who willingly care for patients with a wide array of medical problems. This majority must continue to serve as an example to those who refuse to care for HIV-positive patients, and must make it clear that such actions are professionally intolerable.


The regulatory effect of Genistein on granulosa cell in ovary of rat with PCOS through Bcl-2 and Bax signaling pathways.
The effect of genistein on Bcl-2 and Bax protein expression in the ovarian tissue of rats with polycystic ovarian syndrome (PCOS) was evaluated. Sixty rats were divided into six groups. Rats in the Dose group received genistein at a concentration of either 5 (L-gen), 10 (M-Gen) or 20 (H-Gen) mg per kg of body weight per day. The expression of Bcl-2 mRNA and Bax mRNA was determined by in situ hybridization. Bcl-2 and Bax protein concentration was quantified by ELISA. The results showed that the expression of Bcl-2 mRNA and Bcl-2 protein was significantly higher in the high genistein Dose group (H-Gen) when compared to the Model group (MG) (P<0.05). Genistein induced higher expression of the Bcl-2 gene at the transcriptional and translational level. Treatment with genistein resulted in an improvement of ovarian function with Bcl-2 expression being enhanced and Bax expression being suppressed. These alterations may be due to the structural and functional modifications that take place in these cells, and could be related to apoptotic changes that occur in rats with PCOS.


Four-Photon Absorption Iron Complex for Magnetic Resonance/Photoacoustic Dual-Model Imaging and an Enhanced Ferroptosis Process.
Four-photon absorption (4PA) multimodal therapeutic agent applied to tumor ferroptosis process tracking is rarely reported. In this paper, two functionalized terpyridine iron complexes (TD-FeCl3, TD-Fe-TD) with four-photon absorption properties were designed and synthesized. The four-photon absorption cross sections of TD-FeCl3 reached 6.87 × 10-74cm8·s3·photon-3. Due to its strong near-infrared absorption, TD-FeCl3 has excellent photoacoustic imaging (PAI) capability for accurate PA imaging. TD-FeCl3 has an efficient longitudinal electron relaxation rate (r1 = 2.26 mM-1 s-1) and high spatial resolution, which can be applied as T1-weighted magnetic resonance imaging (MRI) contrast agent for tumor imaging in vivo. In addition, Fe3+ as a natural ferroptosis tracer, TD-FeCl3, is able to deplete glutathione (GSH) effectively, which can further enhance the ferroptosis process. We found that the series of cheap transition metal complexes has four-photon absorption activity and can be used as multimodal (MRI/PAI) diagnostic agents for tumor tracing processes.


Add-back therapy: extending safety and efficacy of GnRH analogues in the gynecologic patient.
GnRH analogues have been demonstrated to be effective medical therapy for symptomatic endometriosis. The use of these agents has been limited to 6 months due to hypoestrogenic side effects. A variety of steroidal and nonsteroidal add-back regimens have been used in an effort to eliminate such side effects while maintaining efficacy in order to enhance compliance, safety and duration such side effects while maintaining efficacy in order to enhance compliance, safety and duration of administration of these agents. Only 3 regimens have been shown to be efficacious in prolonging analogue use beyond 6 months by reducing vasomotor symptoms as well as preventing significant bone mineral density loss. These include daily norethindrone acetate 5 mg alone or in conjunction with conjugated equine estrogens 0.625 mg daily, as well as norethindrone 2.5 mg daily in conjunction with an organic bisphosphonate. With further investigation, such regimens may allow safe prolongation of GnRH analogue use without sacrificing efficacy in those endometriosis patients with severe pelvic pain.


A novel sphingosine kinase inhibitor induces autophagy in tumor cells.
The sphingolipids ceramide, sphingosine, and sphingosine 1-phosphate (S1P) regulate cell signaling, proliferation, apoptosis, and autophagy. Sphingosine kinase-1 and -2 (SK1 and SK2) phosphorylate sphingosine to form S1P, shifting the balanced activity of these lipids toward cell proliferation. We have previously reported that pharmacological inhibition of SK activity delays tumor growth in vivo. The present studies demonstrate that the SK2-selective inhibitor 3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide (ABC294640) induces nonapoptotic cell death that is preceded by microtubule-associated protein light chain 3 cleavage, morphological changes in lysosomes, formation of autophagosomes, and increases in acidic vesicles in A-498 kidney carcinoma cells. ABC294640 caused similar autophagic responses in PC-3 prostate and MDA-MB-231 breast adenocarcinoma cells. Simultaneous exposure of A-498 cells to ABC294640 and 3-methyladenine, an inhibitor of autophagy, switched the mechanism of toxicity to apoptosis, but decreased the potency of the SK2 inhibitor, indicating that autophagy is a major mechanism for tumor cell killing by this compound. Induction of the unfolded protein response by the proteasome inhibitor N-(benzyloxycarbonyl)leucinylleucinylleucinal Z-Leu-Leu-Leu-al (MG-132) or the heat shock protein 90 inhibitor geldanamycin synergistically increased the cytotoxicity of ABC294640 in vitro. In severe combined immunodeficient mice bearing A-498 xenografts, daily administration of ABC294640 delayed tumor growth and elevated autophagy markers, but did not increase terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive cells in the tumors. These data suggest that ABC294640 promotes tumor cell autophagy, which ultimately results in nonapoptotic cell death and a delay of tumor growth in vivo. Consequently, ABC294640 may effectively complement anticancer drugs that induce tumor cell apoptosis.


Sexually transmissible infection and HIV management among men who have sex with men with and without HIV: survey of medical practitioners who are members of the Australasian Society for HIV Medicine.
Rates of HIV in New South Wales (NSW) have been stable, but have increased significantly in other Australian states. The reasons for this are unknown and may be associated with differences in the management of sexually transmissible infections (STI) and HIV in different states in Australia. Our aim was to determine if the use of suppressive treatment for genital herpes, the treatment of HIV or STI screening practices were different between states in Australia. This study was a cross-sectional survey of medical practitioners who are S100 prescribers and members of the Australian Society for HIV Medicine. In general, there were no differences between the clinical practices of practitioners in NSW and other states except that in NSW fewer practitioners tested HIV-positive men who have sex with men (MSM) for syphilis annually (NSW 78% v. others 87%, P = 0.04) or treated MSM with advanced HIV disease (CD4 < 150 x 10(6) cells L(-1)) with acicylovir in the absence of herpes simplex virus (HSV) (NSW 4% v. others 13%, P = 0.03), and more practitioners in NSW tested HIV-negative MSM for HSV type-specific serology (NSW 21% v. others 11%, P = 0.02). It is unlikely that the minor differences in HSV and HIV treatment or STI screening practices among practitioners in NSW and other Australian states explains the differences in HIV notifications between these two areas.


Transition Readiness Not Associated With Measures of Health in Youth With IBD.
It remains unclear how transition readiness is associated with various domains of health in children and young adults. Our objective was to describe the transition readiness of children and young adults with inflammatory bowel disease (IBD) and examine its associations with demographic factors, IBD activity, and measures of physical, psychological, and social health. We recruited children ages 12 to 17 and young adults ages 18 to 20 from 2 internet-based cohorts sponsored by the Crohn's & Colitis Foundation. Participants self-reported demographics, IBD activity, transition readiness, health-related quality of life, and Patient-Reported Outcomes Information Systems domains of physical, psychological, and social health. Among 361 pediatric and 119 adult participants, age and female sex were associated with transition readiness. The association was greater in the pediatric cohort. Having IBD in remission was associated with worse transition readiness in the pediatric cohort only (beta = 0.3; P = 0.003). Health-related quality of life and Patient-Reported Outcomes Information Systems measures of fatigue, pain interference, and sleep disturbance were not associated with transition readiness in either children or adults. We observed few small associations between psychological or social health and transition readiness. Better transition readiness was associated with greater anxiety in adults (beta = -0.02; P = 0.02) and greater peer relationships among children (beta = 0.01; P = 0.009). In children and young adults with IBD, transition readiness was associated with older age and female sex. Associations between transition readiness and physical, psychological, and social health were either small, inconsistent across age groups, or nonexistent.


Assessment of A- to B- DNA Transitions Utilizing the Drude Polarizable Force Field.
In addition to the well-characterized B-form of DNA, duplex DNA can adopt various conformations, such as A or Z-DNA. Though less common, these structures can be induced biologically through protein or ligand interactions or experimentally with niche environmental conditions, such as high salt concentrations or in mixed water-ethanol. Reproducing these alternate structures through molecular dynamics simulations in recent years has been quite challenging with the currently available force fields, simulation techniques, and time scales. In this study, the Drude polarizable force field is tested for its ability to facilitate transitions between A-DNA and B-DNA or maintain A-DNA. Though transitions away from B-DNA were observed in high concentrations of ethanol, the resulting structures had hybrid properties taken from both B-DNA and A-DNA structures. This was also true for A-DNA in ethanol, which lost some of the A-DNA properties that it was expected to maintain. When B-DNA was tested in high salt environments, the resulting B-DNA structures showed no distinguishable differences with the increasing salt concentrations tested. These results with the Drude FF and recent results with additive force fields suggest that at present the current additive and polarizable force fields do not facilitate a complete transition between B- to A-DNA conformations under the conditions simulated. At present, the Drude FF favors A-B DNA hybrid structures when simulated in nonphysiological conditions.


The primary occurrence of BRAF(V600E) is a rare clonal event in papillary thyroid carcinoma.
BRAF(V600E) is considered a primary event, a negative prognostic marker, and a site for pharmacological intervention in papillary thyroid carcinoma (PTC). We asked whether BRAF(V600E) can occur as a subclonal event in PTC and whether this and other oncogenes can coexist in the same tumor. We determined by pyrosequencing the percentage of mutant BRAF, NRAS, and KRAS alleles in a series of conventional PTC. We also analyzed the BRAF mutation status in PTC cell clones in culture. BRAF(V600E) alleles were present in 41 of 72 PTC (56.9%) in the range 44.7 to 5.1% of total BRAF alleles. In four PTC samples, mutant BRAF alleles were about 50%, being therefore compatible with a clonal heterozygous mutation. In 27 PTC samples, BRAF(V600E) alleles were in the range of 25 to 5.1%. This finding was confirmed after exclusion of the presence of a large contamination by lymphoreticular cells and by the analysis of PTC cells selected by laser capture. Analysis of clones derived from a single cell confirmed the presence of two distinct PTC populations with wild-type or mutated BRAF. Simultaneous subclonal BRAF and KRAS mutations were demonstrated in two PTC. These data demonstrate that clonal BRAF(V600E) is a rare occurrence in PTC, although frequently this cancer consists of a mixture of tumor cells with wild-type and mutant BRAF. These results suggest that BRAF mutation in PTC is a later subclonal event, its intratumoral heterogeneity may hamper the efficacy of targeted pharmacotherapy, and its association with a more aggressive disease should be reevaluated.


Colonies of learning automata.
Originally, learning automata (LAs) were introduced to describe human behavior from both a biological and psychological point of view. In this paper, we show that a set of interconnected LAs is also able to describe the behavior of an ant colony, capable of finding the shortest path from their nest to food sources and back. The field of ant colony optimization (ACO) models ant colony behavior using artificial ant algorithms. These algorithms find applications in a whole range of optimization problems and have been experimentally proved to work very well. It turns out that a known model of interconnected LA, used to control Markovian decision problems (MDPs) in a decentralized fashion, matches perfectly with these ant algorithms. The field of LAs can thus both impart in the understanding of why ant algorithms work so well and may also become an important theoretical tool for learning in multiagent systems (MAS) in general. To illustrate this, we give an example of how LAs can be used directly in common Markov game problems.


Mechanisms of desensitization and resensitization of proteinase-activated receptor-2.
Proteinase-activated receptor-2 (PAR-2) is a G-protein-coupled receptor that is expressed by intestinal epithelial cells, which are episodically exposed to pancreatic trypsin in the intestinal lumen. Trypsin cleaves PAR-2 to expose a tethered ligand, which irreversibly activates the receptor. Thus, PAR-2 may desensitize and resensitize by novel mechanisms. We examined these mechanisms in kidney epithelial cells, stably expressing human PAR-2, and intestinal epithelial cells, which naturally express PAR-2. Trypsin stimulated a prompt increase in [Ca2+]i, due to mobilization of intracellular Ca2+, followed by a sustained plateau, due to influx of extracellular Ca2+. Repeated application of trypsin caused marked desensitization of this response, which is due in part to (a) irreversible cleavage of the receptor by trypsin and (b) protein kinase C-mediated termination of signaling. Trypsin exposure resulted in internalization of PAR-2 into early endosomes and then lysosomes; but endocytosis was not the mechanism of rapid desensitization. Thus, activated PAR-2 is endocytosed and degraded. The Ca2+ response to trypsin resensitized by 60-90 min. Brefeldin A, which disrupted Golgi stores of PAR-2, and cycloheximide, which inhibited protein synthesis, markedly attenuated resensitization. Thus, PAR-2-mediated Ca2+ mobilization desensitizes by irreversible receptor cleavage, protein kinase C-mediated termination of signaling, and PAR-2 targeting to lysosomes. It resensitizes by mobilization of large Golgi stores and synthesis of new receptors.


Mothers' work patterns and Children's cognitive achievement: Evidence from the India Human Development survey.
As female labor force participation increases globally, the relationship between maternal employment and children's development remains unclear. Using data from the India Human Development Survey (2005), we investigate the link between maternal employment and children's arithmetic and reading achievement. We develop a work pattern typology that goes beyond standard measures of employment and captures work intensity and its compatibility with child-rearing in a transitional economy. We find that the relationship between maternal employment and children's outcomes is not unidimensional. For example, children of self-employed mothers are not disadvantaged compared to those with stay-at-home mothers, but maternal employment in salaried jobs or wage work outside the home is negatively associated with cognitive skills in children. However, this negative association is reversed at higher levels of maternal education, suggesting greater access to resources and flexibility associated with better jobs mitigate the negative aspects of maternal employment posed by time constraints. Additionally, maternal employment is associated with maternal involvement in schoolwork and financial investment in academic activities, providing evidence that both time and resources devoted to children's education are significant.


Stress, the Autonomic Nervous System, and the Immune-kynurenine Pathway in the Etiology of Depression.
The autonomic nervous system is one of the major neural pathways activated by stress. In situations that are often associated with chronic stress, such as major depressive disorder, the sympathetic nervous system can be continuously activated without the normal counteraction of the parasympathetic nervous system. As a result, the immune system can be activated with increased levels of proinflammatory cytokines. These inflammatory conditions have been repeatedly observed in depression. In the search for the mechanism by which the immune system might contribute to depression, the enhanced activity of indoleamine 2,3- dioxygenase by pro-inflammatory cytokines has been suggested to play an important role. Indoleamine 2,3-dioxygenase is the first enzyme in the kynurenine pathway that converts tryptophan to kynurenine. Elevated activity of this enzyme can cause imbalances in downstream kynurenine metabolites. This imbalance can induce neurotoxic changes in the brain and create a vulnerable glial-neuronal network, which may render the brain susceptible to depression. This review focuses on the interaction between stress, the autonomic nervous system and the immune system which can cause imbalances in the kynurenine pathway, which may ultimately lead to major depressive disorder.


ND6 gene "lost" and found: evolution of mitochondrial gene rearrangement in Antarctic notothenioids.
Evolution of Antarctic notothenioids in the frigid and oxygen-rich Southern Ocean had led to remarkable genomic changes, most notably the gain of novel antifreeze glycoproteins and the loss of oxygen-binding hemoproteins in the icefish family. Recently, the mitochondrial (mt) NADH dehydrogenase subunit 6 (ND6) gene and the adjacent transfer RNA(Glu) (tRNA(Glu)) were also reportedly lost. ND6 protein is crucial for the assembly and function of Complex I of the mt electron transport chain that produces adenosine triphosphate (ATP) essential for life; thus, ND6 absence would be irreconcilable with Antarctic notothenioids being thriving species. Here we report our discovery that the ND6 gene and tRNA(Glu) were not lost but had been translocated to the control region (CR) from their canonical location between ND5 and cytochrome b genes. We characterized the CR and adjacent sequences of 22 notothenioid species representing all eight families of Notothenioidei to elucidate the mechanism and evolutionary history of this mtDNA rearrangement. Species of the three basal non-Antarctic families have the canonical vertebrate mt gene order, whereas species of all five Antarctic families have a rearranged CR bearing the embedded ND6 (ND6(CR)) and tRNA(Glu), with additional copies of tRNA(Thr), tRNA(Pro), and noncoding region in various lineages. We hypothesized that an initial duplication of the canonical mt region from ND6 through CR occurred in the common ancestor to the Antarctic clade, and we deduced the succession of loss or modification of the duplicated region leading to the extant patterns of mt DNA reorganization that is consistent with notothenioid evolutionary history. We verified that the ND6(CR) gene in Antarctic notothenioids is transcribed and therefore functional. However, ND6(CR)-encoded protein sequences differ substantially from basal non-Antarctic notothenioid ND6, and we detected lineage-specific positive selection on the branch leading to the Antarctic clade of ND6(CR) under the branch-site model. Collectively, the novel mt ND6(CR) genotype of the Antarctic radiation represents another major molecular change in Antarctic notothenioid evolution and may reflect an adaptive change conducive to the functioning of the protein (Complex I) machinery of mt respiration in the polar environment, driven by the advent of freezing, oxygen-rich conditions in the Southern Ocean.


Sex steroids and the acquisition of bone mass.
Bone mineralization increases with age, height and weight through childhood, with a significant gain during pubertal development. Approximately 37% of bone mass is accumulated between pubertal stages 2-5. The factors driving the pubertal increase of bone mass is not fully known, but a crucial role is played by the sex steroids. Patients with central precocious puberty show an increased bone mineral density (BMD) for their chronological age, but appropriate for their bone age and pubertal stage. In girls and boys with hypogonadism, as well as in constitutional delay of puberty, the 'tempo' of puberty seems to be another important determinant of peak bone mass. Hypogonadal patients increase their BMD when treated in adulthood with sex steroid substitutive therapy, but normal adult BMD values are not reached. If these patients start sex steroid therapy at the appropriate age for the onset of pubertal development, however, a greater increase in BMD occurs. Both oestrogen and androgen receptors have been demonstrated in bone cells. Patients with oestrogen resistance or aromatase deficiency had a severely undermineralized skeleton. Reduced area and volume BMD are also present in patients with complete androgen resistant syndrome compared to normal. The pubertal increase of BMD may be the result of the coordinated activation of oestrogen and androgen receptors at the bone level in both sexes. In conclusion, the gonadal secretion of sex steroids, the tempo of puberty, and the normal function of both oestrogen and androgen receptors seem to be important factors in the acquisition of bone mass.


Cannabinoid CB1 receptor in dorsal telencephalic glutamatergic neurons: distinctive sufficiency for hippocampus-dependent and amygdala-dependent synaptic and behavioral functions.
A major goal in current neuroscience is to understand the causal links connecting protein functions, neural activity, and behavior. The cannabinoid CB1 receptor is expressed in different neuronal subpopulations, and is engaged in fine-tuning excitatory and inhibitory neurotransmission. Studies using conditional knock-out mice revealed necessary roles of CB1 receptor expressed in dorsal telencephalic glutamatergic neurons in synaptic plasticity and behavior, but whether this expression is also sufficient for brain functions is still to be determined. We applied a genetic strategy to reconstitute full wild-type CB1 receptor functions exclusively in dorsal telencephalic glutamatergic neurons and investigated endocannabinoid-dependent synaptic processes and behavior. Using this approach, we partly restored the phenotype of global CB1 receptor deletion in anxiety-like behaviors and fully restored hippocampus-dependent neuroprotection from chemically induced epileptiform seizures. These features coincided with a rescued hippocampal depolarization-induced suppression of excitation (DSE), a CB1 receptor-dependent form of synaptic plasticity at glutamatergic neurons. By comparison, the rescue of the CB1 receptor on dorsal telencephalic glutamatergic neurons prolonged the time course of DSE in the amygdala, and impaired fear extinction in auditory fear conditioning. These data reveal that CB1 receptor in dorsal telencephalic glutamatergic neurons plays a sufficient role to control neuronal functions that are in large part hippocampus-dependent, while it is insufficient for proper amygdala functions, suggesting an unexpectedly complex circuit regulation by endocannabinoid signaling in the amygdala. Our data pave the way to a better understanding of neuronal networks in the context of behavior, by fine-tuned interference with synaptic transmission processes.


Premature atherosclerosis in systemic lupus erythematosus.
Premature atherosclerosis is a recognized complication of systemic lupus erythematosus (SLE). Since life expectancy in SLE is improving, premature atherosclerosis is emerging as an ever more important clinical issue. Atherosclerosis begins in the pediatric age group, and interventions directed at prevention should begin in childhood as well. Possible etiologies include dyslipoproteinemia (DL) from the underlying chronic inflammatory disease or from corticosteroid therapy, hypercoagulation due to antiphospholipid antibodies or nephrotic syndrome, vasculitis, and hypertension. A relationship between DL and presence of anticardiolipin antibodies (aCL) has been reported. Dietary therapy is helpful, but many patients continue to have significant DL after both dietary modification and fish oil supplementation. Lipid lowering drugs may be indicated in this subgroup. Potential mechanisms of the DL are discussed. Other strategies to prevent atherosclerosis and its complications are reviewed.


Evidence for a lipoxygenase mechanism in the biosynthesis of epoxide and dihydroxy leukotrienes from 15(S)-hydroperoxyicosatetraenoic acid by human platelets and porcine leukocytes.
Leukocyte preparations convert the hydroperoxy icosatetraenoic acids 5(S)-HPETE and 15(S)-HPETE to the unstable leukotriene epoxides LTA4 and 14,15-LTA4. In several ways, the conversion of 5- or 15-HPETE to leukotriene epoxide bears a formal mechanistic resemblance to the reaction catalyzed by the 12-lipoxygenase in the conversion of arachidonic acid to 12(S)-HPETE. Points of similarity include enzymatic removal of a hydrogen at carbon 10, double bond isomerization, and formation of a new carbon-to-oxygen bond. In the case of 15(S)-HPETE, two 8,15- and an erythro-14,15-dihydroxy acid (8,15- and 14,15-DiHETEs), which result from incorporation of molecular oxygen into each hydroxyl group, are coproducts in the formation of 14,15-LTA4. These facts prompted us to test the hypothesis that the biosynthesis of 14,15-LTA4 and of 8,15- and 14,15-DiHETEs from 15(S)-HPETE occurs by a mechanism similar to that observed in lipoxygenase reactions. Based on the results presented here, we conclude that the biosynthesis of 14,15-LTA4 and of 8,15- and 14,15-DiHETEs from 15(S)-HPETE occurs via a common intermediate and that, moreover, the formation of these metabolites from 15(S)-HPETE is catalyzed by an enzyme with many mechanistic features in common with the 12-lipoxygenase.


Update of humanized animal disease models in studying Graft-versus-host disease.
Graft-versus-host disease (GVHD) is a severe adverse effect that results from bone marrow or peripheral blood cells transplantation and has a high rate of mortality. About 50% of the patients are accompanied with acute Graft-versus-Host Disease (aGVHD) after bone marrow cell transplantation and need systematic treatment. It has an important clinical significance to evaluate the prevention and treatment effects of GVHD. The stable and reliable approaches of humanized animal models are crucial for advancing on the study the biology of GVHD. Relative models transplanting the human immune cells into the mouse body can trigger immunoreaction similar to the humans. As it is a disease triggered by human immune cells, any intervention research prior to clinical treatment has more clinical interrelations compared with the general animal models. In this review, we update the current understanding on humanized animal disease models on studying Graft-versus-host disease and expect to provide more theoretical basis to further study on Graft-versus-host disease.


Distinct microbial communities degrade cellulose diacetate bioplastics in the coastal ocean.
Cellulose diacetate (CDA) is a promising alternative to conventional plastics due to its versatility in manufacturing and low environmental persistence. Previously, our group demonstrated that CDA is susceptible to biodegradation in the ocean on timescales of months. In this study, we report the composition of microorganisms driving CDA degradation in the coastal ocean. We found that the coastal ocean harbors distinct bacterial taxa implicated in CDA degradation and these taxa have not been previously identified in prior CDA degradation studies, indicating an unexplored diversity of CDA-degrading bacteria in the ocean. Moreover, the shape of the plastic article (e.g., a fabric, film, or foam) and plasticizer in the plastic matrix selected for different microbial communities. Our findings pave the way for future studies to identify the specific species and enzymes that drive CDA degradation in the marine environment, ultimately yielding a more predictive understanding of CDA biodegradation across space and time.


[Significance of the heterogeneity of respiratory syncytial viral populations in the development of the epidemic process].
The manifestations of the epidemic process in respiratory syncytial (RS) virus infection induced by the strains of the infective agent, differing in their capacity for reproduction at 39 degrees and 37 degrees C and in their sensitivity to antibodies, were compared. The observation of children in a group (about 80 children simultaneously) with the systematic serological and virological examination of sick and healthy children was the main method in this investigation. The circulation of RS viruses with greater capacity for reproduction at 39 degrees and 37 degrees C and lesser sensitivity to antibodies, i.e. viruses with greater virulence, was accompanied by the increased intensity of manifestations of the epidemic process. An increase in the heterogeneity of RS virus populations isolated at the same period of observation was accompanied by the intensification of the epidemic process, which was manifested by increased morbidity rate and a higher level of contamination in children, an increase in the incidence of outbreaks and in the frequency of RS virus reinfection.


An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption.
The inflammation-resolving lipid mediator resolvin E1 (RvE1) effectively stops inflammation-induced bone loss in vivo in experimental periodontitis. It was of interest to determine whether RvE1 has direct actions on osteoclast (OC) development and bone resorption. Primary OC cultures derived from mouse bone marrow were treated with RvE1 and analysed for OC differentiation, cell survival and bone substrate resorption. Receptor binding was measured using radiolabelled RvE1. Nuclear factor (NF)-kappaB activation and Akt phosphorylation were determined with western blotting. Lipid mediator production was assessed with liquid chromatography tandem mass spectrometry. OC growth and resorption pit formation were markedly decreased in the presence of RvE1. OC differentiation was inhibited by RvE1 as demonstrated by decreased number of multinuclear OC, a delay in the time course of OC development and attenuation of receptor activator of NF-kappaB ligand-induced nuclear translocation of the p50 subunit of NF-kappaB. OC survival and apoptosis were not altered by RvE1. Messenger RNA for both receptors of RvE1, ChemR23 and BLT(1) is expressed in OC cultures. Leukotriene B(4) (LTB(4)) competed with [(3)H]RvE1 binding on OC cell membrane preparations, and the LTB(4) antagonist U75302 prevented RvE1 inhibition of OC growth, indicating that BLT(1) mediates RvE1 actions on OC. Primary OC synthesized the RvE1 precursor 18R-hydroxy-eicosapentaenoic acid and LTB(4). Co-incubation of OC with peripheral blood neutrophils resulted in transcellular RvE1 biosynthesis. These results indicate that RvE1 inhibits OC growth and bone resorption by interfering with OC differentiation. The bone-sparing actions of RvE1 are in addition to inflammation resolution, a direct action in bone remodelling.


Nuclear translocation of apoptosis-inducing factor after focal cerebral ischemia.
Signaling cascades associated with apoptosis contribute to cell death after focal cerebral ischemia. Cytochrome c release from mitochondria and the subsequent activation of caspases 9 and 3 are critical steps. Recently, a novel mitochondrial protein, apoptosis-inducing factor (AIF), has been implicated in caspase-independent programmed cell death following its translocation to the nucleus. We, therefore, addressed the question whether AIF also plays a role in cell death after focal cerebral ischemia. We detected AIF relocation from mitochondria to nucleus in primary cultured rat neurons 4 and 8 hours after 4 hours of oxygen/glucose deprivation. In ischemic mouse brain, AIF was detected within the nucleus 1 hour after reperfusion after 45 minutes occlusion of the middle cerebral artery. AIF translocation preceded cell death, occurred before or at the time when cytochrome c was released from mitochondria, and was evident within cells showing apoptosis-related DNA fragmentation. From these findings, we infer that AIF may be involved in neuronal cell death after focal cerebral ischemia and that caspase-independent signaling pathways downstream of mitochondria may play a role in apoptotic-like cell death after experimental stroke.


Maternal common mental disorder and infant growth--a cross-sectional study from Malawi.
The objective of the study was to investigate the association between maternal common mental disorder (CMD) and infant growth in rural Malawi. A cross-sectional study was conducted at a district hospital child health clinic. Participants were consecutive infants due for measles vaccination, and their mothers. Mean infant weight-for-age and length-for-age z-scores were compared between infants of mothers with and without CMD as measured using the self-reporting questionnaire (SRQ). Of 519 eligible infants/mothers, 501 were included in the analysis. Median infant age was 9.9 months. 29.9% of mothers scored 8 or above on the SRQ indicating CMD. Mean length-for-age z-score for infants of mothers with CMD (-1.50 SD 1.24) was significantly lower than for infants of mothers without CMD (-1.11 SD 1.12) Student's t-test: P = 0.001. This association was confirmed in multivariate analysis. Mean weight-for-age z-score for infants of mothers with CMD (-1.77 SD 1.16) was lower than for infants of mothers without CMD (-1.59 SD 1.09) but this difference was not significant on univariate (Student's t-test: P = 0.097) or multivariate analysis. The study demonstrates an association between maternal CMD and infant growth impairment in rural sub-Saharan Africa.


[Labor management following previous cesarean section].
Between January 1, 1982 and March 31, 1984, 300 patients were delivered at Graz Gynaecological Clinic who had undergone Caesarean section during their previous delivery or deliveries at the clinic. It was possible to deliver 166 patients (55.3%) of their children vaginally. The rate of spontaneous labour was as high as 91.8% in a group of 61 women who had given birth vaginally once or several times either before or since the Caesarean section. Successful vaginal delivery occurred in 73.5% or 80.6% if the indication for the previous Caesarean section was a breech presentation or a foetal distress, and in 31.7% or 30.6% of those patients whose indication for their previous Caesarean section was a cephalopelvic disproportion or a prolonged labour. The Caesarean section had to be repeated in a total of 134 parturients (44.7%). Of these, the second Caesarean section was indicated primarily (electively) in 29.1%, secondarily in 70.9%. A rupture in the area of the old Caesarean scar occurred in 5 out of 300 cases (1.7%). In four cases this was diagnosed intraoperatively, and once during post partum palpation of the uterine cavity.


Contact lens correction of patients with Marfan syndrome.
Marfan syndrome, a genetic connective tissue disorder, manifests many problems: high myopia, astigmatism, crystalline lens subluxation, and cataracts. No published studies have described the contact lens corrections that can be used with Marfan syndrome patients. This report describes the variety of contact lens modalities used for a subpopulation of patients with Marfan syndrome. The clinical records of eight patients with Marfan syndrome (16 eyes) from two hospital-based contact lens practices were retrospectively reviewed. Seven different contact lens modalities were used for this subpopulation. Mean unaided visual acuities were 20/296, while mean best-corrected optimal spectacle refraction visual acuities were 20/33. Contact lenses improved the mean visual acuity to 20/27. Patients wore the contact lenses for an average of 12 hours per day. Complications of contact lens wear occurred in approximately 70% of eyes and included neovascularization, giant papillary conjunctivitis, 3 and 9 o'clock staining, and central superficial punctate staining. Additionally, ocular non-contact lens-related complications occurred in 50% of patients. A variety of contact lens designs may be used during the care of patients with Marfan syndrome. However, patients may experience an increased rate of complications associated with contact lens wear or unrelated to lens wear, and thus they deserve more intensive follow-up care than non-Marfan syndrome patients.


[Correlation between MCP-1, HbA1c and glomerular filtration in nondiabetic patients].
This study aims investigate if nondiabetic subjects with fasting glucose < 126 mg/dL but altered HbA1c already have lower estimated glomerular filtration (eGFR) and high serum MCP-1 levels in comparison to nondiabetics with normal HbA1c, independent of other metabolic changes. Data were derived from the database of the CAMELIA (cardio-metabolic-renal family) study, a cross sectional study performed between July 2006 and December 2007, with participants recruited from the Family Doctor Program, Niterói, RJ. An independent association between changes in HbA1c (≥ 5.7 and < 6.5% versus < 5.7%) and decreased eGFR rate was found. The HbA1c was shown to be a marker of metabolic changes in nondiabetic subjects with fasting glucose < 126 mg/dL, particularly in women and blacks. These observations support the use of HbA1c levels in strategies for early intervention and prevention of chronic diseases such as diabetes mellitus and chronic kidney disease.