Expression of metabolic, tissue remodeling, oxidative stress, and inflammatory pathways in mammary tissue during involution in lactating dairy cows. Histological and functional changes associated with involution in the mammary gland are partly regulated by changes in gene expression. At 42 d postpartum, Holstein cows underwent a period of 5 d during which they were milked 1X daily until complete cessation of milking. Percutaneous mammary biopsies (n = 5/time point) were obtained on d 1, 5, 14, and 21 relative to the start of 1X milking for transcript profiling via qPCR of 57 genes associated with metabolism, apoptosis/proliferation, immune response/inflammation, oxidative stress, and tissue remodeling. Not surprisingly, there was clear downregulation of genes associated with milk fat synthesis (FASN, ACACA, CD36, FABP3, SCD) and lipid-related transcription regulation (SREBF1, SREBF2). Similar to milk fat synthesis-related genes, those encoding proteins required for glucose uptake (SLC2A1), casein synthesis (CSN2, CSN3), and lactose synthesis (LALBA) decreased during involution. Unlike metabolic genes, those associated with immune response and inflammation (C3, LTF, SAA3), oxidative stress (GPX1, SOD2), and pro-inflammatory cytokine signaling (SPP1, TNF) increased to peak levels by d 14 from the start of 1X milking. These adaptations appeared to be related with tissue remodeling as indicated by upregulation of proteins encoding matrix proteinases (MMP2), IGFBP3, and transcriptional regulation of apoptosis/cell proliferation (MYC). In contrast, the concerted upregulation of STAT3, TGFB1, and TGFB1R during the first 14 d was suggestive of an activation of these signaling pathways probably as an acute response to regulate differentiation and/or mammary cell survival upon the onset of a marked pro-inflammatory and oxidative stress response induced by the gradual reduction in milk removal. Results suggest a central role of STAT3, MYC, PPARG, SREBF1, and SREBF2 in regulating concerted alterations in metabolic and cell survival mechanisms, which were induced partly via oxidative stressed-triggered inflammation and the decline in metabolic activity.


Understanding of Abdominal Compartment Syndrome among Pediatric Healthcare Providers. Background. The sparse reporting of abdominal compartment syndrome (ACS) in the pediatric literature may reflect inadequate awareness and recognition among pediatric healthcare providers (HCP). Purpose. To assess awareness of ACS, knowledge of the definition and intraabdominal pressure (IAP) measurement techniques used among pediatric HCP. Method. A written survey distributed at two pediatric critical care conferences. Results. Forty-seven percent of 1107 questionnaires were completed. Participants included pediatric intensivists, pediatric nurses, and others. Seventy-seven percent (n = 513) of participants had heard of ACS. Only 46.8% defined ACS correctly. The threshold IAP value used to define ACS was variable among participants. About one-quarter of participants (83/343), had never measured IAP. Conclusion. Twenty-three percent of HCP surveyed were unaware of ACS. Criteria used to define ACS were variable. Focused education on recognition of ACS and measuring IAP should be promoted among pediatric HCP.


Two-hour lactate clearance predicts negative outcome in patients with cardiorespiratory insufficiency. Objective. To evaluate 2-hour lactate clearance as a prognostic marker in acute cardiorespiratory insufficiency. Design. Prospective observational study. Setting. Emergency Department (ED) and 16-bed medical High Dependency Unit (HDU). Methods and Main Results. 95 consecutive admissions from the ED for acute cardiorespiratory insufficiency were prospectively enrolled. Arterial lactate concentration was assessed at ED arrival and 1, 2, 6, and 24 hours later. The predictive value of 2-hour lactate clearance was evaluated for negative outcomes defined as hospital mortality or need for endotracheal intubation versus positive outcomes defined as discharge or transfer to a general medical ward. Logistic regression and ROC curves found 2-hour lactate clearance >15% was a strong predictor of negative outcome (P < .0001) with a sensitivity of 86% (95%CI = 67%-95%) and a specificity of 91% (95%CI = 82%-96%), Positive predictive value was 80% (95%CI = 61%-92%), and negative predictive value was 92% (95%CI = 84%-98%). Conclusions. Systematic monitoring of lactate clearance at 2 hours can be used in to identify patients at high risk of negative outcome and perhaps to tailor more aggressive therapy. Equally important is that a 2-hour lactate clearance >15% is highly predictive of positive outcome and may reassure clinicians that the therapeutic approach is appropriate.


Increased Survivorship and Altered Cytokine Profile from Treatment of Influenza A H1N1-Infected Mice with Ekybion: A Drug Complex of Natural Extracts and Inorganic Compounds. Ekybion is a drug complex of 16 natural extracts and inorganic compounds designed to treat a variety of respiratory pathogens of bacterial and viral origin. It is licensed throughout Europe for the treatment of respiratory tract infections from equine parainfluenza type 3 and equine herpes virus type 1 in equine stables. The purpose of this paper was to test the efficacy of Ekybion on a well-developed animal model of influenza A infection and determine a mode of action. Experiments were performed with Balb/c mice infected with a lethal dose of influenza A/PR/8/34 H1N1 virus and treated with nebulized Ekybion every 8 h in a time-dependant or dose-dependant fashion. These experiments showed that mice treated prior to infection with Ekybion had a higher survival rates (~46%) compared with untreated animals (~0%). Paradoxically, these mice showed no significant difference in lung virus titer or weight loss. There was, however, a decrease in the level of GM-CSF, IL-6, and G-CSF cytokines in the lungs of Ekybion-treated, infected mice. It is possible that decreases in proinflammatory cytokines may have contributed to increased survivorship in Ekybion-treated influenza-infected mice.


Investigation of single and multidomain Pb(In(0.5)Nb(0.5))O(3)-Pb(Mg(1∕3)Nb(2∕3))O(3)-PbTiO(3) crystals with mm2 symmetry. The piezoelectric properties of Pb(In(0.5)Nb(0.5))O(3)-Pb(Mg(1∕3)Nb(2∕3))O(3)-PbTiO(3) crystals with various engineered domain configurations were investigated. Rhombohedral and monoclinic∕orthorhombic crystals poled along their crystallographic [011] directions were found to possess macroscopic mm2 symmetry, with "2R" and "1O" domain, respectively. Crystals with the "2R" domain configuration were found to exhibit high extensional piezoelectric coefficients d(33) (∼1300 pC∕N) and d(32) (∼-1680 pC∕N), while crystals with the "1O" configuration possessed high shear coefficients d(15) (∼3500 pC∕N) and d(24) (∼2070 pC∕N), with relatively low extensional piezoelectric coefficients d(33) (∼340 pC∕N) and d(32) (∼-260 pC∕N). The observed results were explained by "polarization rotation" model, as related to their respective domain configurations.


A grounded theory study of homeopathic practitioners' perceptions and experiences of the homeopathic consultation. Research into the homeopathic consultation has largely focused on patients' experiences, although the practitioner is a crucial component of the therapeutic context and may have an important part in optimizing health outcomes. Therefore the aim of this qualitative research was to gain an in-depth understanding of homeopathic practitioners' perceptions and experiences of the consultation. Medical and non-medical homeopaths were sampled from the registers of the Faculty and Society of Homeopaths. Two phases of data collection were employed. Phase 1 used in depth face-to-face interviews enabling the development of an initial model of the homeopathic consultation. Phase 2 involved observations of homeopathic consultations and practitioner reflective diaries in order to confirm, refute, or enlarge the model. Using the constant comparative method of grounded theory five main categories emerged, exploring the journey, finding the level, responding therapeutically, understanding self, and connecting, forming a model entitled "a theoretical model of a UK classical homeopathic consultation" which describes how homeopaths view and enact the consultation process. This study suggests that the process of identifying and prescribing the remedy is embedded in the consultation, highlighting the interconnectedness of the whole homeopathic consultation and aspects of the consultation that are unique and specific to homeopathy.


High-resolution coregistered intravascular imaging with integrated ultrasound and optical coherence tomography probe. We report an integrated ultrasound (US) and optical coherence tomography (OCT) probe and system for intravascular imaging. The dual-function probe is based on a 50 MHz focused ring US transducer, with a centric hole for mounting OCT probe. The coaxial US and light beams are steered by a 45° mirror to enable coregistered US∕OCT imaging simultaneously. Lateral resolution of US is improved due to focused ultrasonic beam. Mirror effects on US were investigated and invitro imaging of a rabbit aorta has been carried out. The combined US-OCT system demonstrated high resolution in visualizing superficial arterial structures while retaining deep penetration of ultrasonic imaging.


Germinal Cell Aplasia in Kif18a Mutant Male Mice Due to Impaired Chromosome Congression and Dysregulated BubR1 and CENP-E. Chromosomal instability during cell division frequently causes cell death or malignant transformation. Orderly chromosome congression at the metaphase plate, a paramount process to vertebrate mitosis and meiosis, is controlled by a number of molecular regulators, including kinesins. Kinesin-8 (Kif18A) functions to control mitotic chromosome alignment at the mid-zone by negative regulation of kinetochore oscillation. Here the authors report that disrupting Kif18a function results in complete sterility in male but not in female mice. Histological examination reveals that Kif18a(-/-) testes exhibit severe developmental impairment of seminiferous tubules. Testis atrophy in Kif18a(-/-) mice is caused by perturbation of microtubule dynamics and spindle pole integrity, leading to chromosome congression defects during mitosis and meiosis. Depletion of KIF18A via RNAi causes mitotic arrest accompanied by unaligned chromosomes and increased microtubule nucleating centers in both GC-1 and HeLa cells. Prolonged depletion of KIF18A causes apoptosis due to perturbed microtubule dynamics. Further studies reveal that KIF18A silencing results in degradation of CENP-E and BubR1, which is accompanied by premature sister chromatid separation. KIF18A physically interacts with BubR1 and CENP-E, and this interaction is modulated during mitosis. Combined, the studies indicate that KIF18A is essential for normal chromosome congression during cell division and that the absence of KIF18A function causes severe defects in microtubule dynamics, spindle integrity, and checkpoint activation, leading to germinal cell aplasia in mice.


Electromyogenic Artifacts and Electroencephalographic Inferences Revisited. Recent years have witnessed a renewed interest in using oscillatory brain electrical activity to understand the neural bases of cognition and emotion. Electrical signals originating from pericranial muscles represent a profound threat to the validity of such research. Recently, McMenamin et al (2010) examined whether independent component analysis (ICA) provides a sensitive and specific means of correcting electromyogenic (EMG) artifacts. This report sparked the accompanying commentary (Olbrich, Jödicke, Sander, Himmerich & Hegerl, in press), and here we revisit the question of how EMG can alter inferences drawn from the EEG and what can be done to minimize its pernicious effects. Accordingly, we briefly summarize salient features of the EMG problem and review recent research investigating the utility of ICA for correcting EMG and other artifacts. We then directly address the key concerns articulated by Olbrich and provide a critique of their efforts at validating ICA. We conclude by identifying key areas for future methodological work and offer some practical recommendations for intelligently addressing EMG artifact.


Ethical Conduct in Research Involving Human Beings In Brazil: Diagnosis of Research Ethics Committee. OBJECTIVE: Diagnose ethical conduct in research involving human beings in Brazil and the last 10 years of activity by the Human Research Ethics Committee of the Health Department - Federal District - CEP/SES/DF. METHODS: This work was based on a documentary research, descriptive and retrospective. It examined the database containing records of cases brought before the CEP/SES/DF, corresponding the period of June 1997 to December 2007. Results were generated in Excel program, version 2007. RESULTS: CEP/SES/DF has presented increasing number of research projects submitted to appreciation (n = 1129), composing: 90.4% approved 1.7% disapproved, 7.4% removed/filed and 0.5% excluded. Of these projects, 83% belonged to Group III, 18% multi-centered projects and 10% protocols with foreign participation. Time for approval has decreased over the years (30 to 60 days). Frequent pendencies: End of Free and Informed Consent (30%), Cover Sheet (25%), Methodology (20%), Curriculum vitae (12%), Budget (9%), and Others (4%). CONCLUSION: The assessment of the CEP/SES/DF activities, during a ten-year period has shown its commitment to the legitimacy of research ethics review and scientific production SES/DF. There were some weaknesses such as difficulty in monitoring the accompaniment of the research; interruption of works due to adverse drug reaction; gaps or errors in the protocol submitted by the researcher. These situations are the achieving targets for the elaboration of specific criteria.


Physical Activity and Adherence to Mediterranean Diet Increase Total Antioxidant Capacity: The ATTICA Study. We studied the association of physical activity and adherence to the Mediterranean diet, in total antioxidant capacity (TAC). A random sample of 1514 men and 1528 women was selected from Attica region. Physical activity was assessed with a translated version of the validated "International Physical Activity Questionnaire" (iPAQ), and dietary intake through a validated Food Frequency Questionnaire (FFQ). Adherence to the Mediterranean diet was assessed by the MedDietScore that incorporated the inherent characteristics of this diet. TAC was positively correlated with the degree of physical activity (P < .05). TAC was also positively correlated with MedDietScore (r = 0.24, P < .001). Stratified analysis by diet status revealed that the most beneficial results were observed to highly active people as compared to inactive, who also followed the Mediterranean diet (288 ± 70 μmol/L, 230 ± 50 μmol/L, resp.), after adjusting for various confounders. Increased physical activity and greater adherence to the Mediterranean diet were associated with increased total antioxidant capacity.


CpG oligodeoxynucleotides enhance the efficacy of adoptive cell transfer using tumor infiltrating lymphocytes by modifying the Th1 polarization and local infiltration of Th17 cells. Adoptive cell transfer immunotherapy using tumor infiltrating lymphocytes (TILs) was an important therapeutic strategy against tumors. But the efficacy remains limited and development of new strategies is urgent. Recent evidence suggested that CpG-ODNs might be a potent candidate for tumor immunotherapy. Here we firstly reported that CpG-ODNs could significantly enhance the antitumor efficacy of adoptively transferred TILs in vivo accompanied by enhanced activity capacity and proliferation of CD8(+) T cells and CD8(+) T cells, as well as a Th1 polarization immune response. Most importantly, we found that CpG-ODNs could significantly elevate the infiltration of Th17 cells in tumor mass, which contributed to anti-tumor efficacy of TILs in vivo. Our findings suggested that CpG ODNs could enhance the anti-tumor efficacy of adoptively transferred TILs through modifying Th1 polarization and local infiltration of Th17 cells, which might provide a clue for developing a new strategy for ACT based on TILs.


Xanthogranulomatous salpingitis associated with a large uterine leiomyoma. A case of xanthogranulomatous salpingitis (XGS) associated with a large uterine leiomyoma in a 50-year-old woman is presented. Xanthogranulomatous inflammation is an uncommon form of chronic inflammation that is destructive to affected organs. It is characterized by the presence of lipid-filled macrophages with admixed lymphocytes, plasma cells, and neutrophils. A review of the literature revealed that most patients with XGS have a clinical history of long-standing pelvic inflammatory disease (PID) or, less often, endometriosis. We report a case lacking a history of either PID or endometriosis but with a concurrent large uterine leiomyoma. Although the exact etiology in this case was not clear, the leiomyoma may have played a contributory role in pathogenesis.


Total laparoscopic conservative surgery for an intramural ectopic pregnancy. A 38-year-old woman, gravida 3, para 1 with a history of a left salpingectomy for an ectopic pregnancy was admitted for treatment of a presumed ectopic pregnancy. Transvaginal sonography revealed an ill-defined gestational sac and fetal heart beat within the fundal myometrium adjacent to the left cornua. Laparoscopy was performed for a suspected left cornual pregnancy or intramural pregnancy. A cystic mass 3 cm in diameter was visible within the fundal myometrium. Total laparoscopic removal of the gestational sac was performed, and the uterus was preserved. Pathologic evaluation of the excised mass demonstrated chorionic villi involving the myometrium. In the literature, only one other case describing the laparoscopic removal of an intramural pregnancy has been reported. However, in the prior report, the patient still required hysterectomy after conservative surgery. Therefore, this is the first report of the successful treatment of an intramural pregnancy exclusively with laparoscopy.


The role of the IL-12 cytokine family in directing T-cell responses in oral candidosis. Candida albicans is an opportunistic fungal pathogen that normally exists as a harmless commensal in humans. In instances where host debilitation occurs, Candida can cause a range of clinical infections, and whilst these are primarily superficial, effecting mucosal membranes, systemic infections can develop in severely immunocompromised individuals. The mechanism of host immunity during commensal carriage of C. albicans has been intensively studied. In this paper, we present the most recent information concerning host recognition of C. albicans leading to cytokine production and the subsequent T-cell responses generated in response to C. albicans. Particular focus is given to the role of the IL-12 cytokine family including IL-12, IL-23, IL-27, and IL-35, in host immunity to Candida. CD4(+) T-cells are considered crucial in the regulation of immunity and inflammation. In this regard, the role of Th1/2, helper cells, together with the recently identified Th17 and Treg cells in candidosis will be discussed. Understanding the detailed mechanisms that underlie host immunity to Candida not only will be of benefit in terms of the infections caused by this organism but could also be exploited in the development of therapeutic interventions for other diseases.


Long-Term Gynecological Outcomes in Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. Background. Our knowledge on long-term outcome in CAH remains incomplete. Methods. In a prospective study (33 CAH patients, 33 age-matched controls), reproductive outcomes, self-rating of genital appearance and function, and sexuality were correlated to degree of initial virilisation, genotype, and surgery. Results. Patients had larger median clitoral lengths (10.0 mm [range 2-30] versus 3.5 [2-8], P < .001), shorter vaginal length (121 mm [100-155] versus 128 [112-153], P = .12), lower uterine volumes (29.1 ml [7.5-56.7] versus 47.4 [15.9-177.5], P = .009), and higher ovarian volumes (4.4 ml [1.3-10.8] versus 2.8 [0.6-10.8], P = .09) than controls. Satisfaction with genital appearance was lower and negatively correlated to degree of initial virilisation (r(s) = ≤-0.39, P ≤ .05). More patients had never had intercourse (P = .001), and age at 1st intercourse was higher (18 yrs versus 16 yrs, P = .02). Conclusion. Despite overall acceptable cosmetic results, reproductive outcomes were suboptimal, supporting that multidisciplinary teams should be involved in adult follow up of CAH patients.


Functional Promiscuity of Homologues of the Bacterial ArsA ATPases. The ArsA ATPase of E. coli plays an essential role in arsenic detoxification. Published evidence implicates ArsA in the energization of As(III) efflux via the formation of an oxyanion-translocating complex with ArsB. In addition, eukaryotic ArsA homologues have several recognized functions unrelated to arsenic resistance. By aligning ArsA homologues, constructing phylogenetic trees, examining ArsA encoding operons, and estimating the probable coevolution of these homologues with putative transporters and auxiliary proteins unrelated to ArsB, we provide evidence for new functions for ArsA homologues. They may play roles in carbon starvation, gas vesicle biogenesis, and arsenic resistance. The results lead to the proposal that ArsA homologues energize four distinct and nonhomologous transporters, ArsB, ArsP, CstA, and Acr3.


Gadolinium Enhanced MR Coronary Vessel Wall Imaging at 3.0 Tesla. Purpose. We evaluated the influence of the time between low-dose gadolinium (Gd) contrast administration and coronary vessel wall enhancement (LGE) detected by 3T magnetic resonance imaging (MRI) in healthy subjects and patients with coronary artery disease (CAD). Materials and Methods. Four healthy subjects (4 men, mean age 29 ± 3 years and eleven CAD patients (6 women, mean age 61 ± 10 years) were studied on a commercial 3.0 Tesla (T) whole-body MR imaging system (Achieva 3.0 T; Philips, Best, The Netherlands). T1-weighted inversion-recovery coronary magnetic resonance imaging (MRI) was repeated up to 75 minutes after administration of low-dose Gadolinium (Gd) (0.1 mmol/kg Gd-DTPA). Results. LGE was seen in none of the healthy subjects, however in all of the CAD patients. In CAD patients, fifty-six of 62 (90.3%) segments showed LGE of the coronary artery vessel wall at time-interval 1 after contrast. At time-interval 2, 34 of 42 (81.0%) and at time-interval 3, 29 of 39 evaluable segments (74.4%) were enhanced. Conclusion. In this work, we demonstrate LGE of the coronary artery vessel wall using 3.0 T MRI after a single, low-dose Gd contrast injection in CAD patients but not in healthy subjects. In the majority of the evaluated coronary segments in CAD patients, LGE of the coronary vessel wall was already detectable 30-45 minutes after administration of the contrast agent.


Newly developed fully covered metal stent for unresectable malignant biliary stricture. We herein report two patients with unresectable malignant biliary stricture who underwent stenting with a newly developed fully-covered metal stent. In the first case of lower-middle bile duct cancer, a stent was placed through the stenosis. In the second case of middle bile duct stricture due to lymph node metastases from gallbladder cancer, a stent was placed in the bile duct across the stenosis. No procedure-related complications were observed. Unevenness of the outer surface and a low shortening ratio are expected to lessen the occurrence of complications characteristic of covered metal stents such as stent migration and bile duct kinking.


Adhesion of Pathogenic Bacteria to Food Contact Surfaces: Influence of pH of Culture. The adhesion of Aeromonas hydrophila, Escherichia coli O157:H7, Salmonella Enteritidis, and Staphylococcus aureus to hydrophobic and hydrophilic surfaces in cultures with different pHs (6, 7, and 8) was studied. The results indicated that the type of material had no effect on the attachment capacity of microorganisms, while environmental pH influenced the adhesion of A. hydrophila, E. coli, and S. aureus to both solid substrates. The attachment of S. Enteritidis (P > .05) was not affected by the type of substrate or the culture pH, whereas E. coli displayed the weakest affinity for both polystyrene and glass surfaces. No correlation was established between the physicochemical properties of the materials, or the bacterial and the rate of bacterial adhesion, except for S. aureus. Photomicrographs have shown that surfaces were contaminated by small clusters of S. Enteritidis while S. aureus invaded the food contact surfaces in the form of small chains or cell aggregates.


Genotoxicity revaluation of three commercial nitroheterocyclic drugs: nifurtimox, benznidazole, and metronidazole. Nitroheterocyclic compounds are widely used as therapeutic agents against a variety of protozoan and bacterial infections. However, the literature on these compounds, suspected of being carcinogens, is widely controversial. In this study, cytotoxic and genotoxic potential of three drugs, Nifurtimox (NFX), Benznidazole (BNZ), and Metronidazole (MTZ) was re-evaluated by different assays. Only NFX reduces survival rate in actively proliferating cells. The compounds are more active for base-pair substitution than frameshift induction in Salmonella; NFX and BNZ are more mutagenic than MTZ; they are widely dependent from nitroreduction whereas microsomal fraction S9 weakly affects the mutagenic potential. Comet assay detects BNZ- and NFX-induced DNA damage at doses in the range of therapeutically treated patient plasma concentration; BNZ seems to mainly act through ROS generation whereas a dose-dependent mechanism of DNA damaging is suggested for NFX. The lack of effects on mammalian cells for MTZ is confirmed also in MN assay whereas MN induction is observed for NFX and BNZ. The effects of MTZ, that shows comparatively low reduction potential, seem to be strictly dependent on anaerobic/hypoxic conditions. Both NFX and BNZ may not only lead to cellular damage of the infective agent but also interact with the DNA of mammalian cells.


Roles of beta2- and beta3-adrenoceptor polymorphisms in hypertension and metabolic syndrome. Hypertension, diabetes mellitus (especially type 2 diabetes mellitus), metabolic syndrome and obesity are rapidly growing public health problems. Sympathetic nerve activation is observed in obesity, hypertension and diabetes mellitus, which have strong genetic as well as environmental determinants. Reduced energy expenditure and resting metabolic rate are predictive of weight gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The thermogenic effects of catecholamines in obesity have been mainly mediated via the β2- and β3-adrenergic receptors in humans. Further, β2-adrenoceptors importantly influence vascular reactivity and may regulate blood pressure. Genetic polymorphistns of the β-adrenoceptor gene have been shown to alter the function of several adrenoceptor subtypes and thus to modify the response to catecholamine. β2-adrenoceptor polymorphisms (Arg16Gly, Gln27Glu, and Thr164Ile) have been studied in relation to hypertension. Genetic variations in the β3-adrenoceptor (i.e. Try64Arg variant) are also associated with both obesity and hypertension. However, the precise relationships of the polymorphisms of β2- and β3-adrenoceptor genes with sympathetic nervous system activity, hypertension, and metabolic syndrome have not been fully clarified. This paper will discuss the current topics involving the influence of the sympathetic nervous system and β2- and β3- adrenoceptor polymorphisms in hypertension and metabolic syndrome.


Multimodality imaging of chronic ischemia. Although ischemic cardiomyopathy is commonly caused by chronic obstructive coronary disease, the mechanism of the cause is still under investigation. We present echocardiographic strain, magnetic resonance, and histology findings in a chronic ischemia model in preclinical study. This case illustrates the features of multimodality imaging in chronic obstructive coronary disease and gives us great insight into understanding the mechanism of ischemic cardiomyopathy.


Surface lipids as multifunctional mediators of skin responses to environmental stimuli. Skin surface lipid (SSL) film is a mixture of sebum and keratinocyte membrane lipids, protecting skin from environment. Its composition is unique for the high percentage of long chain fatty acids, and of the polyterpenoid squalene, absent in other human tissues, and in non-human Primates sebum. Here, the still incomplete body of information on SSL as mediators of external chemical, physical, and microbial signals and stressors is revised, focusing on the central event of the continuous oxidative modification induced by the metabolic activity of residential and pathological microbial flora, natural or iatrogenic UV irradiation, exposure to chemicals and cosmetics. Once alpha-tocopherol and ubiquinol-10 antioxidant defences of SSL are overcome, oxidation of squalene and cholesterol gives rise to reactive by-products penetrating deeper into skin layers, to mediate local defensive inflammatory, photo-protective, immune reactions or, at higher concentrations, inducing local but also systemic immune depression, ultimately implicating skin cancerogenesis. Qualitative modifications of SSL represent a pathogenetic sign of diagnostic value in dermatological disorders involving altered sebum production, like pytiriasis versicolor, acne, atopic or seborrheic dermatitis, as well as photo-aging. Achievements of nutriceutical interventions aimed at restoring normal SSL composition and homeostasis are discussed, as feasible therapeutic goals and major means of photo-protection.


Consensus in Guidelines for Evaluation of DSD by the Texas Children's Hospital Multidisciplinary Gender Medicine Team. The Gender Medicine Team (GMT), comprised of members with expertise in endocrinology, ethics, genetics, gynecology, pediatric surgery, psychology, and urology, at Texas Children's Hospital and Baylor College of Medicine formed a task force to formulate a consensus statement on practice guidelines for managing disorders of sexual differentiation (DSD) and for making sex assignments. The GMT task force reviewed published evidence and incorporated findings from clinical experience. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess the quality of evidence presented in the literature for establishing evidence-based guidelines. The task force presents a consensus statement regarding specific diagnostic and therapeutic issues in the management of individuals who present with DSD. The consensus statement includes recommendations for (1) laboratory workup, (2) acute management, (3) sex assignment in an ethical framework that includes education and involvement of the parents, and (4) surgical management.


Inhibitory effect of chinese propolis on phosphatidylcholine-specific phospholipase C activity in vascular endothelial cells. To understand the mechanisms underlying the anti-inflammatory action of Chinese propolis, we investigated its effect on the activity of phosphatidylcholine-specific phospholipase C (PC-PLC) that plays critical roles in control of vascular endothelial cell (VEC) function and inflammatory responses. Furthermore, p53 and reactive oxygen species (ROS) levels and mitochondrial membrane potential (Δψm) were investigated. Our data indicated that treatment of Chinese propolis 6.25 and 12.5 μg/ml for 12 hours increased VEC viability obviously. Exposure to Chinese propolis 6.25, 12.5, and 25 μg/ml for 6 and 12 hours significantly decreased PC-PLC activity and p53 level, and ROS levels were depressed by Chinese propolis 12.5 μg/ml and 25 μg/ml dramatically. The Δψm of VECs was not affected by Chinese propolis at low concentration but disrupted by the propolis at 25 μg/ml significantly, which indicated that Chinese propolis depressed PC-PLC activity and the levels of p53 and ROS in VECs but disrupted Δψm at a high concentration.


Animal models of typical heterotopic ossification. Heterotopic ossification (HO) is the formation of marrow-containing bone outside of the normal skeleton. Acquired HO following traumatic events is a common and costly clinical complication. In contrast, hereditary HO is rarer, progressive, and life-threatening. Substantial effort has been directed towards understanding the mechanisms underlying HO and finding efficient treatments. However, one crucial limiting factor has been the lack of relevant animal models. This article reviews the major currently available animal models, summarizes some of the insights gained from these studies, and discusses the potential future challenges and directions in HO research.


Causes and mechanisms of intrauterine hypoxia and its impact on the fetal cardiovascular system: a review. Until today the role of oxygen in the development of the fetus remains controversially discussed. It is still believed that lack of oxygen in utero might be responsible for some of the known congenital cardiovascular malformations. Over the last two decades detailed research has given us new insights and a better understanding of embryogenesis and fetal growth. But most importantly it has repeatedly demonstrated that oxygen only plays a minor role in the early intrauterine development. After organogenesis has taken place hypoxia becomes more important during the second and third trimester of pregnancy when fetal growth occurs. This review will briefly adress causes and mechanisms leading to intrauterine hypoxia and their impact on the fetal cardiovascular system.


The availability of a recombinant anti-SNAP antibody in VHH format amplifies the application flexibility of SNAP-tagged proteins. Antibodies are indispensable reagents in basic research, and those raised against tags constitute a useful tool for the evaluation of the biochemistry and biology of novel proteins. In this paper, we describe the isolation and characterization of a single-domain recombinant antibody (VHH) specific for the SNAP-tag, using Twist2 as a test-protein. The antibody was efficient in western blot, immunoprecipitation, immunopurification, and immunofluorescence. The sequence corresponding to the anti-SNAP has been subcloned for large-scale expression in vectors that allow its fusion to either a 6xHis-tag or the Fc domain of rabbit IgG2 taking advantage of a new plasmid that was specifically designed for VHH antibodies. The two different fusion antibodies were compared in immunopurification and immunofluorescence experiments, and the recombinant protein SNAP-Twist2 was accurately identified by the anti-SNAP Fc-VHH construct in the nuclear/nucleolar subcellular compartment. Furthermore, such localization was confirmed by direct Twist2 identification by means of anti-Twisit2 VHH antibodies recovered after panning of the same naïve phage display library used to isolate the anti-SNAP binders. Our successful localization of Twist2 protein using the SNAP-tag-based approach and the anti-Twist2-specific recombinant single-domain antibodies opens new research possibilities in this field.


Reproductive technologies and genomic selection in cattle. The recent development of genomic selection induces dramatic changes in the way genetic selection schemes are to be conducted. This review describes the new context and corresponding needs for genomic based selection schemes and how reproductive technologies can be used to meet those needs. Information brought by reproductive physiology will provide new markers and new improved phenotypes that will increase the efficiency of selection schemes for reproductive traits. In this context, the value of the reproductive techniques including assisted embryo based reproductive technologies (Multiple Ovaluation Embryo Transfer and Ovum pick up associated to in vitro Fertilization) is also revisited. The interest of embryo typing is discussed. The recent results obtained with this emerging technology which are compatible with the use of the last generation of chips for genotype analysis may lead to very promising applications for the breeding industry. The combined use of several embryo based reproductive technologies will probably be more important in the near future to satisfy the needs of genomic selection for increasing the number of candidates and to preserve at the same time genetic variability.


Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver. Thiazolidinediones are a class of Peroxisome Proliferator Activated Receptor γ (PPARγ) agonists that reduce insulin resistance in type 2 diabetic patients. Although no detectable hepatic toxicity has been evidenced in animal studies during preclinical trials, these molecules have nevertheless induced hepatic adverse effects in some treated patients. The mechanism(s) of hepatotoxicity remains equivocal. Several studies have been conducted using PCR analysis and microarray technology to identify possible target genes and here we review the data obtained from various in vivo and in vitro experimental models. Although PPARγ is expressed at a much lower level in liver than in adipose tissue, PPARγ agonists exert various PPARγ-dependent effects in liver in addition to PPARγ-independent effects. Differences in effects are dependent on the choice of agonist and experimental conditions in rodent animal studies and in rodent and human liver cell cultures. These effects are much more pronounced in obese and diabetic liver. Moreover, our own recent studies have shown major interindividual variability in the response of primary human hepatocyte populations to troglitazone treatment, supporting the occurrence of hepatotoxicity in only some individuals.


Orthodontic Bracket Manufacturing Tolerances and Dimensional Differences between Select Self-Ligating Brackets. In all manufacturing processes there are tolerances; however, orthodontic bracket manufacturers seldom state the slot dimensional tolerances. This experiment develops a novel method of analyzing slot profile dimensions using photographs of the slot. Five points are selected along each wall, and lines are fitted to define a trapezoidal slot shape. This investigation measures slot height at the slot's top and bottom, angles between walls, slot taper, and the linearity of each wall. Slot dimensions for 30 upper right central incisor self-ligating stainless steel brackets from three manufacturers were evaluated. Speed brackets have a slot height 2% smaller than the nominal 0.559 mm size and have a slightly convergent taper. In-Ovation brackets have a divergent taper at an average angle of 1.47 degrees. In-Ovation is closest to the nominal value of slot height at the slot base and has the smallest manufacturing tolerances. Damon Q brackets are the most rectangular in shape, with nearly 90-degree corners between the slot bottom and walls. Damon slot height is on average 3% oversized.


The Relationship between the Transforming Growth Factor β1 T29C Gene Polymorphism and Left Ventricular Geometry and Function in Hypertensive Subjects. The distribution of the T29C TGFβ1 gene polymorphism was analyzed in 198 hypertensives with left ventricular hypertrophy (LVH) and in 235 hypertensives without LVH. Circulating TGFβ1 levels, procollagen type III levels, microalbuminuria, and left ventricular geometry and function were evaluated in all the hypertensives with LVH subgrouped according to T29C TGFβ1 gene polymorphism. Circulating TGFβ1 was evaluated by ELISA technique, procollagen type III by a specific radioimmunoassay, microalbuminuria by radioimmunoassay, and left ventricular geometry and function by echocardiography. All groups were comparable for gender, age, and sex. Regarding T29C TGFβ1 gene polymorphism, prevalence of TC or CC genotypes was significantly (P < .05) higher in hypertensives with LVH than hypertensives without LVH TC and CC LVH hypertensives were characterized by a higher prevalence of subjects with microalbuminuria (P < .05 TC and CC versus TT), by increased levels of TGFβ1, procollagen type III, urinary albumin excretion, LVM, LVM/h(2.7), and lower values of left ventricular ejection fraction (P < .05 TC and CC versus TT). Our data suggest that T29C TGFβ1 gene polymorphism was associated with clinical characteristics adequate to recognize a subset of LVH hypertensives with a higher severity of hypertension.


Gene/Environment interaction in atherosclerosis: an example of clinical medicine as seen from the evolutionary perspective. Evolutionary medicine is the application of evolution theory to understanding health and disease. It provides a complementary scientific approach to the present mechanistic explanations that dominate medical science, and particularly medical education. The chronic multifactorial disease of atherosclerosis clearly illustrates the Darwinian paradigm. Recent research, combining the effects of genes and environment, has provided surprising clues to the pathogenesis of this major public health problem. This example makes a strong case for recognizing evolution biology as a basic science for medicine.


Genome-wide association study of coronary artery disease. Coronary artery disease (CAD) is a multifactorial disease with environmental and genetic determinants. The genetic determinants of CAD have previously been explored by the candidate gene approach. Recently, the data from the International HapMap Project and the development of dense genotyping chips have enabled us to perform genome-wide association studies (GWAS) on a large number of subjects without bias towards any particular candidate genes. In 2007, three chip-based GWAS simultaneously revealed the significant association between common variants on chromosome 9p21 and CAD. This association was replicated among other ethnic groups and also in a meta-analysis. Further investigations have detected several other candidate loci associated with CAD. The chip-based GWAS approach has identified novel and unbiased genetic determinants of CAD and these insights provide the important direction to better understand the pathogenesis of CAD and to develop new and improved preventive measures and treatments for CAD.


Advances in diagnosis of respiratory virus infections. The diagnosis of respiratory virus infections has evolved substantially in recent years, with the emergence of new pathogens and the development of novel detection methods. While recent advances have improved the sensitivity and turn-around time of diagnostic tests for respiratory viruses, they have also raised important issues such as cost, and the clinical significance of detecting multiple viruses in a single specimen by molecular methods. This article reviews recent advances in specimen collection and detection methods for diagnosis of respiratory virus infections, and discusses the performance characteristics and limitations of these methods.


Noninvasive detection of left-ventricular systolic dysfunction by acoustic cardiography in atrial fibrillation. Objectives. Assessment of left ventricular (LV) systolic function in patients with atrial fibrillation can be difficult. Acoustic cardiography provides several parameters for quantifying LV systolic function. We evaluated the ability of acoustic cardiography to detect LV systolic dysfunction in patients with and without atrial fibrillation. Design. We studied 194 patients who underwent acoustic cardiography and cardiac catheterization including measurement of angiographic ejection fraction (EF) and maximum LV dP/dt. LV systolic dysfunction was defined as LV maximum dP/dt <1600 mmHg/s. Acoustic cardiographic parameters included electromechanical activation time (EMAT) and the systolic dysfunction index (SDI). Results. Acoustic cardiography detected systolic dysfunction with high specificity and moderate sensitivity with similar performance to EF (sensitivity/specificity without afib: EMAT 30/96, SDI 40/90, EF at 35% 30/96; sensitivity/specificity with afib: EMAT 64/82, SDI 59/100, EF at 35% 45/82). Conclusions. Acoustic cardiography can be used for diagnosis of LV systolic dysfunction in atrial fibrillation.


Vascular alterations and sexual function in systemic sclerosis. Sexual dysfunction is common in systemic sclerosis (SSc). Male erectile dysfunction (MED) has been reported in around 80% of subjects and more than half of female patients fulfill criteria for diagnosis as female sexual arousal Disorder (FSAD). While some evidence supports a role for cavernosal fibrosis, abundant data suggest that MED is yet another clinical feature of SSc related to vasculopathy. The contribution of vasculopathy to the more complex issues of female sexual dysfunction is less clear. Inhibitors of Type V phosphodiesterase are effective in men with MED secondary to SSc. Limited study in women suggests inconsistent effects on behavior (frequency) but not on measures related to perfusion. Sexual activity is an important component of quality of life and an important domain for the caregiver to address; it is not clear that it warrants primary consideration as a consistent measure of scleroderma-related vasculopathy.


An NOS3 Haplotype is Protective against Hypertension in a Caucasian Population. The endothelial nitric oxide synthase gene (NOS3) has been implicated in the development of hypertension, although the specific role of variants and haplotypes has not been clarified. In this study, the association of three polymorphisms (promoter T786C, intronic 4a/b, and nonsynonymous G894T) was tested in a case-control sample of 230 patients with essential hypertension and 306 healthy controls. Haplotype analysis was also performed. The mutant allele a(∗) of the 4a/b polymorphism showed a protective effect against hypertension under a dominant model (odds ratio = 0.64, 95% confidence interval (0.44-0.93)), although this effect was not significant after the adjustment for covariates (P = 0.06). The estimated frequency of the haplotype composed of the T786(∗), 4a(∗), and G894(∗) alleles was significantly higher in controls (5.5%) compared to cases (2%). These results indicate that although individual NOS3 polymorphisms are not associated with hypertension, a rare haplotype of the gene might be protective against the development of hypertension.


Microscopic polyangiitis in systemic sclerosis. AAV in SSc is described from the point of view of MPA. Some of reported SSc cases with AAV are thought to exhibit the characteristic clinical manifestations of MPA, although ANCA positivity in SSc is uncommon. MPA is clinically characterized by a multisystemic disease such as RPGN, pulmonary hemorrhage, mononeuritis, and skin involvement, as well as other manifestations in conjunction with high levels of inflammatory activity such as high ESR or CRP. It is also characterized by a high frequency of MPO-ANCA, showing predominant pANCA by IIF. When rapid renal failure or RPGN with active urine sediments, pulmonary hemorrhage and/or systemic inflammatory manifestations are observed in patients with SSc having positive ANCA, the possibility of MPA should always be considered. If SSc patients with MPA have life-threatening visceral involvement such as the above clinical manifestations, the patients should be treated with induction therapy using cyclophosphamide, methotrexate, corticosteroids, or plasmapheresis, etc. according to the severity of the disease soon after the diagnosis of MPA. It is important not to overlook characteristic clinical manifestations of AAV during the course of the disease in SSc in order to diagnose MPA early.


Acne scars: pathogenesis, classification and treatment. Acne has a prevalence of over 90% among adolescents and persists into adulthood in approximately 12%-14% of cases with psychological and social implications. Possible outcomes of the inflammatory acne lesions are acne scars which, although they can be treated in a number of ways, may have a negative psychological impact on social life and relationships. The main types of acne scars are atrophic and hypertrophic scars. The pathogenesis of acne scarring is still not fully understood, but several hypotheses have been proposed. There are numerous treatments: chemical peels, dermabrasion/microdermabrasion, laser treatment, punch techniques, dermal grafting, needling and combined therapies for atrophic scars: silicone gels, intralesional steroid therapy, cryotherapy, and surgery for hypertrophic and keloidal lesions. This paper summarizes acne scar pathogenesis, classification and treatment options.


Post testicular sperm maturational changes in the bull: important role of the epididymosomes and prostasomes. After spermatogenesis, testicular spermatozoa are not able to fertilize an oocyte, they must undergo sequential maturational processes. Part of these essential processes occurs during the transit of the spermatozoa through the male reproductive tract. Since the sperm become silent in terms of translation and transcription at the testicular level, all the maturational changes that take place on them are dependent on the interaction of spermatozoa with epididymal and accessory gland fluids. During the last decades, reproductive biotechnologies applied to bovine species have advanced significantly. The knowledge of the bull reproductive physiology is really important for the improvement of these techniques and the development of new ones. This paper focuses on the importance of the sperm interaction with the male reproductive fluids to acquire the fertilizing ability, with special attention to the role of the membranous vesicles present in those fluids and the recent mechanisms of protein acquisition during sperm maturation.


Pediatric sedation: a global challenge.

Pediatric sedation: a global challenge. Pediatric sedation is a challenge which spans all continents and has grown to encompass specialties outside of anesthesia, radiology and emergency medicine. All sedatives are not universally available and local and national regulations often limit the sedation practice to specific agents and those with specific credentials. Some specialties have established certification and credentials for sedation delivery whereas most have not. Some of the relevant sedation guidelines and recommendations of specialty organizations worldwide will be explored. The challenge facing sedation care providers moving forward in the 21st century will be to determine how to apply the local, regional and national guidelines to the individual sedation practices. A greater challenge, perhaps impossible, will be to determine whether the sedation community can come together worldwide to develop standards, guidelines and recommendations for safe sedation practice.


Bilateral serous retinal detachments associated with accelerated hypertensive choroidopathy. Purpose. We report a case of hypertensive choroidopathy with bilateral serous retinal detachments. Patient. A 50-year-old man underwent bilateral serous retinal detachments. Retinal arteriolar narrowing, vascular tortuosity, and arteriovenous nicking were identified in both eyes. The blood pressure was 206/125 mmHg. The patient was diagnosed with bilateral hypertensive choroidopathy and treated with oral antihypertensive treatment. Results and discussion. One month after antihypertensive treatment, the serous retinal detachments resolved and the visual acuity improved. A patient with those findings should be considered as having hypertensive choroidopathy and treated as soon as possible.


Scleroderma renal crisis: a pathology perspective. Scleroderma renal crisis (SRC) is an infrequent but serious complication of systemic sclerosis (SSc). It is associated with increased vascular permeability, activation of coagulation cascade, and renin secretion, which may lead to the acute renal failure typically associated with accelerated hypertension. The histologic picture of SRC is that of a thrombotic microangiopathy process with prominent small vessel involvement manifesting as myxoid intimal changes, thrombi, onion skin lesions, and/or fibrointimal sclerosis. Renal biopsies play an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in SSc patients, helping to predict the clinical outcome and optimizing patient management. Kidney transplantation may be the only treatment option available for a subset of SRC patients who develop end-stage renal failure despite aggressive angiotensin-converting enzyme inhibitor therapy. However, the posttransplant outcome for SSc patients is currently suboptimal compared to the general renal transplant population.


Prevalence, Awareness, Treatment, and Control of Hypertension in Romania: Results of the SEPHAR Study. East European countries have reported high prevalence of Arterial Hypertension (AHT). In order to investigate the data for Romania, we firstly performed a national survey-the Study for the Evaluation of Prevalence of Hypertension and Cardiovascular Risk in Adult Population in Romania (SEPHAR). A representative population was selected using stratified proportional sampling, including 2017 adult subjects, ≥18 years old. The general prevalence of AHT was 44,92%, higher in men (50,17%) than in women (41,11%) (P < .0001) and predominant in rural areas (49,47%) in comparison to the urban ones (41,58%) (P < .02). AHT awareness attended 44,26%, rising with age, significantly lower in men (34,58%) than in women (52,8%) (P < .0006). We have found a 38,85% proportion of treated hypertensive persons, worse for men (30,11%) then for women (46,56%) (P < .003). The rate of AHT control was 19,88%, with no significant differences between gender. In conclusion, we estimated for Romania a high prevalence of AHT, a level of awareness and treatment lower than in many European countries and a rate of treatment control at the inferior limit of the European average. Males, characterized by a higher prevalence of AHT, were also less aware and less treated than women.


Endosonography-guided biliary drainage with one-step placement of a newly developed fully covered metal stent followed by duodenal stenting for pancreatic head cancer. An 83-year-old man was admitted to our department, presenting with jaundice, fever, and nausea. CT revealed a pancreatic head tumor with duodenal invasion. Endoscopic transpapillary biliary drainage was unsuccessful due to stenosis at the second portion of the duodenum and tumor invasion to the papilla of Vater. Using a convex linear array echoendoscope, a fully-covered metal stent was placed across the puncture tract to bridge the duodenum and the bile duct. After improvement of jaundice, a duodenal metal stent was placed across the stricture of the duodenum. No procedure-related complications occurred. Neither migration nor obstruction of the two stents was observed during the three months followup period. Combination of ESBD using a fully covered metal stent and duodenal stenting is a feasible technique and possibly a less invasive treatment option for malignant biliary and duodenal obstruction compared to surgery.


Penile involvement in Systemic Sclerosis: New Diagnostic and Therapeutic Aspects. Systemic Sclerosis (SSc) is a connective tissue disorder featuring vascular alterations and an immunological activation leading to a progressive and widespread fibrosis of several organs such as the skin, lung, gastrointestinal tract, heart, and kidney. Men with SSc are at increased risk of developing erectile dysfunction (ED) because of the evolution of early microvascular tissutal damage into corporeal fibrosis. The entity of penile vascular damage in SSc patients has been demonstrated by using Duplex ultrasonography and functional infra-red imaging and it is now clear that this is a true clinical entity invariably occurring irrespective of age and disease duration and constituting the ''sclerodermic penis". Once-daily phosphodiesterase type-5 (PDE5) inhibitors improve both sexual function and vascular measures of cavernous arteries by improving surrogate markers of endothelial dysfunction, that is, plasma endothelin-1 and adrenomedullin levels, which may play a potential role in preventing progression of penile fibrosis and ED. Also, the beneficial effect of long-term PDE5i add-on therapy to SSc therapy in the treatment of Raynaud's phenomenon is described.


Interleukin-6 as a potential therapeutic target for pulmonary arterial hypertension. Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biologic activities in immune regulation, hematopoiesis, inflammation, and oncogenesis. Recent accumulating evidence indicates a pathologic role for IL-6 in promoting proliferation of both smooth muscle and endothelial cells in the pulmonary arterioles, resulting in development of pulmonary arterial hypertension (PAH). Here, we describe a patient with mixed connective tissue disease and severe, refractory PAH. Her functional activity and hemodynamic parameters dramatically responded to tocilizumab, a humanized monoclonal antibody to human IL-6 receptor, which was aimed at treating multicentric Castleman's disease. It appears that IL-6 blockade may hold promise as an adjunct drug in treatment of PAH in idiopathic form as well as in association with connective tissue disease.


Quercetin and Bornyl Acetate Regulate T-Lymphocyte Subsets and INF-γ/IL-4 Ratio In Utero in Pregnant Mice. The objective of this study is to investigate the antiabortive effects of Quercetin and Bornvl Acetate and their immunological modulation at maternal-fetal interface. Lipopolysaccharide (LPS) was injected via tail vein to induce abortion in mice which received Quercetin and Bornvl Acetate at days 4-7 of gestation. Uterine CD4+/CD8+ T lymphocytes and IFN-γ/IL-4 of each group (n = 10) were detected by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The ratio of CD4+/CD8+ increased significantly (P < .01) in the uterus of LPS-induced abortion mice. In the Quercetin and Bornvl Acetate pretreated mice followed by LPS administration, the ratio of CD4+/CD8+ dropped to 0.562 ± 0.021, lower than that of LPS-abortion group (P < .01). The mean value of IFN-γ/IL-4 in LPS-treated mice was 0.310 ± 0.066, higher than that of Quercetin and Bornyl Acetate group. The results indicate that Quercetin and Bornyl Acetate have an antiabortive effect through modulation of immunological balance at maternal-fetal interface.


Suppression of ongoing experimental arthritis by a chinese herbal formula (huo-luo-xiao-ling dan) involves changes in antigen-induced immunological and biochemical mediators of inflammation. Rheumatoid arthritis (RA) is one of the major autoimmune diseases of global prevalence. The use of the anti-inflammatory drugs for the treatment of RA is associated with severe adverse reactions and toxicity. This limitation has necessitated the search for novel therapeutic products. We report here a traditional Chinese medicine-based herbal formula, Huo luo xiao ling dan (HLXL), which has potent antiarthritic activity as validated in the rat adjuvant-induced arthritis (AA) model. HLXL (2.3 g/Kg) was fed to Lewis (RT.1(1)) rats daily by gavage beginning at the onset of arthritis and then continued through the observation period. HLXL inhibited the severity of ongoing AA. This suppression of arthritis was associated with significant alterations in the T cell proliferative and cytokine responses as well as the antibody response against the disease-related antigen, mycobacterial heat-shock protein 65 (Bhsp65). There was a reduction in the level of the proinflammatory cytokines IL-17 and IL-1β but enhancement of the anti-inflammatory cytokine IL-10 level. In addition, there was inhibition of both the anti-Bhsp65 antibody response and the serum level of nitric oxide. Thus, HLXL is a promising CAM modality for further testing in RA patients.


Hypoglycemic and Hepatoprotective Activity of Fermented Fruit Juice of Morinda citrifolia (Noni) in Diabetic Rats. Morinda citrifolia is a medicinal plant used to treat diabetes and liver diseases. The fermented fruit juice of the M. Citrifolia (optical density = 1.25) was used to study the hypoglycemic and hepatoprotective properties in diabetes-induced rats. The rats were randomly distributed into 4 groups (control, diabetic experimental, diabetic standard, and diabetic untreated) of 6 each. Diabetes was induced by administering Streptozotocin (50 mg/kg body weight). Fasting blood glucose, body mass, liver tissue glycogen content, and the extent of liver degeneration were assessed. Diabetic experimental animals were treated with M. citrifolia juice (2 ml/kg, twice a day) and diabetic standard with reference hypoglycemic drug, glibenclamide orally for 20 days. Both the groups exhibited a significant reduction in blood glucose level of 150 mg/dl ±15.88 and 125 mg/dl ±3.89, respectively, as compared to diabetic untreated with FBS = 360.0 mg/dl ±15.81, (P < .003). On 10th day of experiment, diabetic experimental animals exhibited a decrease in body mass (10.2 g, 5.11%) which increased significantly by the 20th day (6 g, 3.0%, P < .022). Histological study of liver tissue obtained from untreated diabetic animals revealed significant fatty degeneration as compared to other three groups. The data of this study proved the hypoglycemic and hepatoprotective activity of M. citrifolia.


Use of homeopathy in pediatric oncology in Germany. Homeopathy is a frequently used complementary and alternative medicine (CAM) treatment. We present results comparing responses of homeopathy users (HUs) and users of other forms of CAM (NHUs) in pediatric oncology (PO) in Germany. Differences between these two groups (usage, associated demographic characteristics, previous experience with CAM) are investigated. 186 (45.2%) of the 367 CAM users were exposed to homeopathy. The treatment duration amounted to a median of 601 days for HUs and 282 days for NHUs. Parents with p (127; 76.5%) also used homeopathy for their child's cancer. Nonmedical practitioners played a considerably greater role as source of information than did treating physician. In the majority HUs received their prescriptions from nonmedical practitioners (56%; 29.4% of NHUs). HUs communicate more frequently with their physicians about the CAM-use (77.7% versus 65.2%) and recommend CAM more often than NHUs (94% versus 85.6%). Homeopathy is the most frequently used CAM treatment in PO in Germany. HUs sustain treatment and therapies considerably longer than NHUs. Most families who had used homeopathy before their child was diagnosed with cancer also used homeopathy for the treatment of their child's cancer. Compared to other CAM treatments, patient satisfaction with homeopathy appears to be very high.


Retrosternal percutaneous tracheostomy: an approach for predictably impossible classic tracheostomy. Percutaneous tracheostomy is a routine procedure in intensive care units. In cases of very low position of the larynx, cervical spine deformation, morbid obesity, or neck tumor, performance of the classic tracheostomy is inapplicable. Retrosternal approach to tracheostomy in such 20 patients is herein reported. After preoperative neck computerized tomography to define the neck anatomy, a small suprasternal incision followed by a short retrosternal tissue dissection to expose the trachea was done; the trachea was then catheterized at the level of the 2nd ring in the usual tracheostomy manner. The immediate and late (≥6 months) outcomes were similar to that of the standard tracheostomy. Thus, percutaneous retrosternal tracheostomy is safe in patients with abnormal positioning of the trachea or neck constitution. It is a bedside applicable technique, that, however, requires caution to avoid hazardous vascular complications.


Leptospirosis: An Unusual Cause of ARDS. Severe leptospirosis usually associates shock, jaundice, renal failure, and thrombocytopenia. Massive hemoptysis due to diffuse alveolar haemorrhage may rarely occur leading to an acute respiratory failure and multiple organ failure. We present the case of an acute respiratory distress syndrome caused by a severe leptospirosis. The severity of the respiratory failure contrasted with the absence of significant liver or renal dysfunction. Bedside open lung biopsy was only consistent with a postinfectious BOOP. The diagnosis was retrospective when the niece of the patient presented with similar inaugural symptoms ten days later after being scratched by a wild rat which was considered by our patient as a pet.


Antidiabetic Potentiality of the Aqueous-Methanolic Extract of Seed of Swietenia mahagoni (L.) Jacq. in Streptozotocin-Induced Diabetic Male Albino Rat: A Correlative and Evidence-Based Approach with Antioxidative and Antihyperlipidemic Activities. Antidiabetic, antioxidative, and antihyperlipidemic activities of aqueous-methanolic (2 : 3) extract of Swietenia mahagoni (L.) Jacq. (family Meliaceae) seed studied in streptozotocin-induced diabetic rats. Feeding with seed extract (25 mg 0.25 mL distilled water(-1)100 gm b.w.(-1)rat(-1) day(-1)) for 21 days to diabetic rat lowered the blood glucose level as well as the glycogen level in liver. Moreover, activities of antioxidant enzymes like catalase, peroxidase, and levels of the products of free radicals like conjugated diene and thiobarbituric acid reactive substances in liver, kidney, and skeletal muscles were corrected towards the control after this extract treatment in this model. Furthermore, the seed extract corrected the levels of serum urea, uric acid, creatinine, cholesterol, triglyceride, and lipoproteins towards the control level in this experimental diabetic model. The results indicated the potentiality of the extract of S. mahagoni seed for the correction of diabetes and its related complications like oxidative stress and hyperlipidemia. The extract may be a good candidate for developing a safety, tolerable, and promising neutraceutical treatment for the management of diabetes.


Gene Expression and Serum Cytokine Profiling of Low Stage CLL Identify WNT/PCP, Flt-3L/Flt-3 and CXCL9/CXCR3 as Regulators of Cell Proliferation, Survival and Migration. Gene expression profiling (GEP) of 8 stage 0/I untreated Chronic Lymphocytic Leukemia (CLL) patients showed over-expression of Frizzled 3 (FZD3)/ROR-1 receptor tyrosine kinase (RTK), FLT-3 RTK and CXCR3 G-protein coupled receptor (GPCR). RT-PCR of 24 genes in 21 patients of the WNT pathway corroborated the GEP. Transforming growth factorβ, fibromodulin, TGFβRIII and SMAD2 are also over-expressed by GEP. Serum cytokine profiling of 26 low stage patients showed elevation of IFNγ, CSF3, Flt-3L and insulin-like growth factor binding protein 4. In order to ascertain why CLL cells grow poorly in culture, a GEP of 4 CLL patients cells at 0 hr and 24 hr in culture demonstrated over expression of CXCL5, CCL2 and CXCL3, that may recruit immune cells for survival. Treatment with thalidomide, an immunomodulatory agent, showed elevation of CCL5 by GEP but was not cytotoxic to CLL cells. Our data suggest an interplay of several oncogenic pathways, cytokines and immune cells that promote a survival program in CLL.


Epidemiology, prognosis, and evolution of management of septic shock in a French intensive care unit: a five years survey. Purpose. To evaluate the epidemiology, prognosis, and management of septic shock patients hospitalized in our intensive care unit (ICU). Materiel and Methods. Five-year monocenter observational study including 320 patients. Results. ICU mortality was 54.4%. Independent mortality risk factors were mechanical ventilation (OR = 4.97), Simplify Acute Physiology Score (SAPS) II > 60 (OR = 4.28), chronic alcoholism (OR = 3.38), age >65 years (OR = 2.65), prothrombin ratio <40% (OR = 2.37), and PaO(2)/FiO(2) ratio <150 (OR = 1.91). These six mortality risk factors recovered allow screening immediately septic shock patients with a high mortality risk. Morbidity improved with time (diminution of septic shock complications, increase of the number of days alive free from mechanical ventilation and vasopressors on day 28), concomitant to an evolution of the management (earlier institution of all replacement and medical therapies and more initial volume expansion). There was no difference in mortality. Conclusion. Our study confirms a high mortality rate in septic shock patients despite a new approach of treatment.


Inhibitory Effects of Terminalia catappa on UVB-Induced Photodamage in Fibroblast Cell Line. This study investigated whether Terminalia catappa L. hydrophilic extract (TCLW) prevents photoaging in human dermal fibroblasts after exposure to UVB radiation. TCLW exhibited DPPH free radical scavenging activity and protected erythrocytes against AAPH-induced hemolysis. In the gelatin digestion assay, the rates of collagenase inhibition by TCL methanol extract, TCLW, and its hydrolysates were greater than 100% at the concentration of 1 mg/mL. We found that serial dilutions of TCLW (10-500 μg/mL) inhibited collagenase activity in a dose-dependent manner (82.3% to 101.0%). However, TCLW did not significantly inhibit elastase activity. In addition, TCLW inhibited MMP-1 and MMP-9 protein expression at a concentration of 25 μg/mL and inhibited MMP-3 protein expression at a concentration of 50 μg/mL. TCLW also promoted the protein expression of type I procollagen. We also found that TCLW attenuated the expression of MMP-1, -3, and -9 by inhibiting the phosphorylation of ERK, JNK, and p38. These findings suggest that TCLW increases the production of type I procollagen by inhibiting the activity of MMP-1, -3 and -9, and, therefore, has potential use in anti-aging cosmetics.


Advent of a Link between Ayurveda and Modern Health Science: The Proceedings of the First International Congress on Ayurveda, "Ayurveda: The Meaning of Life-Awareness, Environment, and Health" March 21-22, 2009, Milan, Italy. The First International Congress on Ayurveda was held in Milan, Italy in March 2009 and it has been the first scientific event of this kind in western world. This groundbreaking international congress was devoted to human being as the product of interactions between Awareness, Environment and Health, subjects that the West tends to consider separate and independent, but that are believed deeply connected in Ayurveda, whose interdependence defines "The Meaning of Life". The Congress established a bridge between indian and western philosophy, scientific and biomedical thinking in order to expand knowledge and healthcare. Main attention and address of the invited speakers was on the concept of "relationships" that, connecting living beings with environment, shape Nature itself. This concept is central in Ayurveda but is also common to other western scientific disciplines such as quantum physics and epigenetics that, in the four Sessions of the Congress, were represented by eminent experts. The importance of this event was underlined by the attendance of more than 400 participants and by noteworthy institutional endorsements, that added a significative political dimension of high social impact due to the topical period for CAM acceptance and integration in Europe.


Selective decontamination of the digestive tract reduces pneumonia and mortality. Selective decontamination of the digestive tract (SDD) has been subject of numerous randomized controlled trials in critically ill patients. Almost all clinical trials showed SDD to prevent pneumonia. Nevertheless, SDD has remained a controversial strategy. One reason for why clinicians remained reluctant to implement SDD into daily practice could be that mortality was reduced in only 2 trials. Another reason could be the heterogeneity of trials of SDD. Indeed, many different prophylactic antimicrobial regimes were tested, and dissimilar diagnostic criteria for pneumonia were applied amongst the trials. This heterogeneity impeded interpretation and comparison of trial results. Two other hampering factors for implementation of SDD have been concerns over the risk of antimicrobial resistance and fear for escalation of costs associated with the use of prophylactic antimicrobials. This paper describes the concept of SDD, summarizes the results of published trials of SDD in mixed medical-surgical intensive care units, and rationalizes the risk of antimicrobial resistance and rise of costs associated with this potentially life-saving preventive strategy.


Bone Loss Rate May Interact with Other Risk Factors for Fractures among Elderly Women: A 15-Year Population-Based Study. Aim was to investigate fracture risk (FR) according to bone loss (BL) rate. A random sample of 1652 women aged 53.5 years was measured with dual X-ray absorptiometry in femoral neck in 1989 and 1994 and divided into tertiles of annual BL rate: high >0.84%, moderate 0.13%-0.84%, and low <0.13%. Low trauma energy fractures during following 10 years were recorded. There were no differences in FR between BL tertiles in Cox regression model. Factors predicting lower FR in Cox model were in high tertile: high T-score (HR 0.71; 95% CI 0.54-0.93, P = .012), no sister's fracture (HR 0.35; 0.19-0.64, P = .001), no mother's fracture (HR 0.52; 0.31-0.88, P = .015), in moderate tertile: high T-score (HR 0.69;0.53-0.91, P = .008) and good grip strength (HR 0.98; 0.97-0.99, P = .022). In low tertile there were no predictors for FR. BL predicted FR in women with mother's fracture in univariate and multivariate model (OR 2.6; 1.15-5.7, P = .021) but with sister's fracture this was observed only in multivariate model (OR 2.66; 1.09-6.7, P = .039). Accordingly, the risk factors for postmenopausal fractures, especially mother's fracture, may interact with BL.


Superparamagnetic bifunctional bisphosphonates nanoparticles: a potential MRI contrast agent for osteoporosis therapy and diagnostic. A bone targeting nanosystem is reported here which combined magnetic contrast agent for Magnetic Resonance Imaging (MRI) and a therapeutic agent (bisphosphonates) into one drug delivery system. This new targeting nanoplatform consists of superparamagnetic γFe(2)O(3) nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs) molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI contrast agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRI T2(∗) contrast agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63) show that γFe(2)O(3)@di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system.


Acupuncture on the Endometrial Morphology, the Serum Estradiol and Progesterone Levels, and the Expression of Endometrial Leukaemia-inhibitor Factor and Osteopontin in Rats. Although it is well known that acupuncture has beneficial effects on a variety of medical conditions especially in pain relief, nausea, and vomiting, it remains controversial whether it has positive impact on the female reproduction. The present study aimed to evaluate whether the following endometrial receptivity factors: the endometrial morphology, the hormone concentrations, and the protein expression of endometrial leukaemia-inhibitory factor (LIF) and osteopontin (OPN) could be improved by the acupuncture in clomiphene citrate(CC)-induced rat model during implantation period. Results showed that, compared with the CC group, glandular development advanced, the serum estradiol levels decreased significantly, and the glandular area and endometrial LIF and OPN expression were significantly higher in acupuncture group. There were no significant differences in serum progesterone levels, endometrial thickness, and stromal area between groups. These results suggest that acupuncture can improve certain aspects of endometrial receptivity in CC-induced rat model during implantation period, which might result in endometrial state better to female reproduction.


Vertebroplasty and Kyphoplasty Can Restore Normal Spine Mechanics following Osteoporotic Vertebral Fracture. Osteoporotic vertebral fractures often lead to pain and disability. They can be successfully treated, and possibly prevented, by injecting cement into the vertebral body, a procedure known as vertebroplasty. Kyphoplasty is similar, except that an inflatable balloon is used to restore vertebral body height before cement is injected. These techniques are growing rapidly in popularity, and a great deal of recent research, reviewed in this paper, has examined their ability to restore normal mechanical function to fractured vertebrae. Fracture reduces the height and stiffness of a vertebral body, causing the spine to assume a kyphotic deformity, and transferring load bearing to the neural arch. Vertebroplasty and kyphoplasty are equally able to restore vertebral stiffness, and restore load sharing towards normal values, although kyphoplasty is better at restoring vertebral body height. Future research should optimise these techniques to individual patients in order to maximise their beneficial effects, while minimising the problems of cement leakage and adjacent level fracture.


Geographic variation in osteoporotic hip fracture incidence: the growing importance of asian influences in coming decades. Studies over the last few decades have demonstrated geographic variation in the incidence of hip fracture across continents and among different parts of the same region. This paper studies the epidemiology of hip fracture worldwide, with special emphasis on the geographic variation among Asian countries. Using the Pubmed database, keywords that were employed included hip fracture, incidence rate, geographic variation, osteoporosis, and epidemiology. Articles were chosen based on the basis of (1) focus: studies that were said to specifically focus on geographic variation in hip fracture from different continents with a focus on Asia; (2) language: studies that were in English; (3) methods: studies that used statistical tests to examine hip fracture incidence rates. The highest hip fracture rates are seen in Scandinavian countries and the US and the lowest in African countries. Fracture rates are intermediate in Asian populations. Among different ethnic populations, the highest fracture rates are seen in Caucasians and the lowest in blacks. There is also a north-south gradient, particularly in Europe, where more hip fractures occur in North Europe compared to the South.


Prevalence of dietary supplement use in patients with proven or suspected cardiovascular disease. Systematic search of bibliographic databases was conducted to describe the prevalence of dietary supplement use in cardiac patients. Included for review were studies that investigated supplement use in people with cardiovascular risk factors or proven cardiovascular disease. Databases searched were Medline, EMBASE, CINAHL, AMED, Meditext, H&S and IPA. Over five hundred articles were retrieved and twenty studies met the criteria for this review. Dietary supplements were taken by a median 36% (interquartile range: 26-42%) of cardiac patients; 36% (IQR 18-43%) reported taking a vitamin/mineral supplement and 12% (IQR 7-21%) used herbal supplements. Many users indicated that supplements were taken specifically for heart health and 16-64% of users reported using supplements alongside prescription medications. However 39-95% of treating physicians were unaware of patients' supplement use. Dietary supplement use in patients with cardiovascular disease appears common, as does the concurrent use of supplements with prescription medicines. This information is often not communicated to doctors and treating physicians may need to be more proactive in asking about supplement use.


Osteoporosis-related simultaneous four joints fractures and dislocation after a seizure: a case report. A case of steroid-induced osteoporosis-related multiple fractures and dislocations are described after a seizure is reported. Patient had two years history of steroid use with no supplement or antiresorptive therapy. There was a delay in the diagnosis which affected an otherwise good outcome in such situations. It is recommended that patients on steroid should be given calcium, vitamin D, and an antiresorptive. Furthermore, a meticulous clinical examination is required in patients who are on steroids and suffer epileptic seizures to rule out skeletal injury.


Calcaneal BMD Obtained by Dual X-Ray and Laser Predicts Future Hip Fractures-A Prospective Study on 4 398 Swedish Women. The predictive value of dual X-ray and laser (DXL) calcaneal BMD (BMD(DXL)) on hip fractures was prospectively studied in 4,398 females aged 55 to 99 years. The average follow-up period was 3 years and 11 months with a total of 17,270 person years. Fractures were identified from the national patient register. After inclusion, 130 females sustained a hip fracture. The age adjusted hazard ratio for T-score <-2.5 versus >-2.5 was 2.64. Of all patients who sustained a hip fracture 78% had a T-score of -2.5 or below. The annual hip fracture rate was 0.26% at T-scores ≥-2, but 1.5% at T-scores ≤-2.5. The area under curve for the model including calcaneal BMD(DXL), follow-up time, and age to prospectively predict hip fractures was 0.84. Conclusions. Calcaneal BMD(DXL) obtained by DXL Calscan predicts hip fractures and may therefore be suitable for diagnosing osteoporosis and for predicting fracture risk.


Is childhood obesity associated with bone density and strength in adulthood? Associations between childhood obesity and adult bone traits were assessed among 62 obese premenopausal women, of which 12 had been obese since childhood (ObC), and 50 had gained excess weight in adulthood (ObA). Body composition and bone mineral content (BMC) of the total body, spine, and proximal femur were assessed with DXA. Total cross-sectional area and cortical (diaphyseal CoD) and trabecular (epiphyseal TrD) bone density of the radius and tibia were measured with pQCT. Compared to ObA-group, ObC-group was 5.2 cm taller having 2.5 and 3.5 kg more lean and fat mass, respectively. Depending on the statistical adjustment, ObC-group had 5-10% greater TrD both in tibia and in radius. The remaining bone traits did not significantly differ between the groups. Current preliminary observations bring up an interesting question whether childhood obesity can result in denser trabecular bone in adulthood. However, prudence must be exercised in the statistical adjustment.


Sclerostin.

Sclerostin. The striking clinical benefits of intermittent parathyroid hormone in osteoporosis have begun a new era of skeletal anabolic agents. One potential new agent is monoclonal antibody to sclerostin, a potent inhibitor of osteoblastogenesis.


The significance of soy protein and soy bioactive compounds in the prophylaxis and treatment of osteoporosis. Osteoporosis is defined as a progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Although bone mass and quality is mainly determined genetically, many other factors, including lifestyle and nutrition also have an impact on bone health. It has been suggested that dietary protein intake may be a risk factor for osteoporosis, and high-protein diets are associated with increased bone loss. Many scientists have examined the relationship between types of protein and urinary calcium excretion, and found that although animal protein was associated with increased urinary calcium excretion, soy protein was not. There is sufficient evidence suggesting soy isoflavones may have potential benefits for bone. Soy protein with naturally occurring phytoestrogens, mainly isoflavones protect against bone loss and synthetic soy ipriflavone in some studies has been shown to favorably affect, but a cause and effect relationship has not been established between the consumption of ipriflavone and maintenance of bone mineral density in post-menopausal women. Therefore it is too early to recommend it as a supplement for this group of women.


Scientific basis for the potential use of melatonin in bone diseases: osteoporosis and adolescent idiopathic scoliosis. The objective of this paper was to analyze the data supporting the possible role of melatonin on bone metabolism and its repercussion in the etiology and treatment of bone pathologies such as the osteoporosis and the adolescent idiopathic scoliosis (AIS). Melatonin may prevent bone degradation and promote bone formation through mechanisms involving both melatonin receptor-mediated and receptor-independent actions. The three principal mechanisms of melatonin effects on bone function could be: (a) the promotion of the osteoblast differentiation and activity; (b) an increase in the osteoprotegerin expression by osteoblasts, thereby preventing the differentiation of osteoclasts; (c) scavenging of free radicals generated by osteoclast activity and responsible for bone resorption. A variety of in vitro and in vivo experimental studies, although with some controversial results, point toward a possible role of melatonin deficits in the etiology of osteoporosis and AIS and open a new field related to the possible therapeutic use of melatonin in these bone diseases.


Ewing's Sarcoma and Second Malignancies. Ewing's sarcoma (ES) is a rare tumor that is most common in children and young adults. Late effects of ES therapy include second cancers, a tragic outcome for survivors of such a young age. This paper will explore the frequencies and types of malignancies that occur after ES. Additionally, it will review how second malignancies have changed with the shift in treatment from high-dose radiation to chemotherapy regimens including alkylators and epipodophyllotoxins. The risk of additional cancers in ES survivors will also be compared to survivors of other childhood cancers. Finally, the possible genetic contribution to ES and second malignancies will be discussed.


Development of a multicommutated flow system with chemiluminometric detection for quantification of gentamicin in pharmaceuticals. A new flow procedure based on multicommutation with chemiluminometric detection was developed to quantify gentamicin sulphate in pharmaceutical formulations. This approach is based on gentamicin's ability to inhibit the chemiluminometric reaction between luminol and hypochlorite in alkaline medium, causing a decrease in the analytical signal. The inhibition of the analytical signal is proportional to the concentration of gentamicin sulphate, within a linear range of 1 to 4 μg mL(-1) with a coefficient variation <3%. A sample throughput of 55 samples h(-1) was obtained. The developed method is sensitive, simple, with low reagent consumption, reproducible, and inexpensive, and when applied to the analysis of pharmaceutical formulations (eye drops and injections) it gave results with RSD between 1.10 and 4.40%.


Discovery of a Novel Chemical Class of mGlu(5) Allosteric Ligands with Distinct Modes of Pharmacology. We previously discovered a positive allosteric modulator (PAM) of the metabotropic glutamate receptor subtype 5 (mGlu(5)) termed 4 N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-hydroxybenzamide (CPPHA) that elicits receptor activation through a novel allosteric site on mGlu(5), distinct from the classical mGlu(5) negative allosteric modulator (NAM) MPEP allosteric site. However, a shallow structure-activity relationship (SAR), poor physiochemical properties, and weak PAM activity at rat mGlu(5) limited the utility of CPPHA to explore allosteric activation of mGlu(5) at a non-MPEP site. Thus, we performed a functional high-throughput screen (HTS) and identified a novel mGlu(5) PAM benzamide scaffold, exemplified by VU0001850 (EC(50) = 1.3 μM, 106% Glu(max)) and VU0040237 (EC(50) = 350 nM, 84% Glu Max). An iterative parallel synthesis approach delivered 22 analogues, optimized mGlu(5) PAM activity to afford VU0357121 (EC(50) = 33 nM, 92% Glu(max)), and also revealed the first non-MPEP site neutral allosteric ligand (VU0365396). Like CPPHA, PAMs within this class do not appear to bind at the MPEP allosteric site based on radioligand binding studies. Moreover, mutagenesis studies indicate that VU0357121 and related analogues bind to a yet uncharacterized allosteric site on mGlu(5), distinct from CPPHA, yet share a functional interaction with the MPEP site.


Radiotherapy for soft tissue sarcoma of the proximal lower extremity. Soft-tissue sarcoma (STS) is a histopathologically diverse group of tumors accounting for approximately 10,000 new malignancies in the US each year. The proximal lower extremity is the most common site for STS, accounting for approximately one-third of all cases. Coordinated multimodality management in the form of surgery and radiation is often critical to local control, limb preservation, and functional outcome. Based on a review of currently available Medline literature and professional experience, this paper provides an overview of the treatment of STS of the lower extremity with a particular focus on the modern role of radiotherapy.


Airbag pneumonitis.

Airbag pneumonitis. The widespread and mandatory use of airbags has resulted in various patterns of injuries and complications unique to their use. Airbags have been implicated in a spectrum of pulmonary conditions ranging from exacerbation of asthma, reactive airway diseases to new onset asthma. We report a case of inhalational chemical pneumonitis that developed after exposure to the airbag fumes.


Forebrain ischemia triggers GABAergic system degeneration in substantia nigra at chronic stages in rats. The long-term consequences of forebrain ischemia include delayed Parkinson's syndrome. This study revealed delayed neurodegeneration in the substantia nigra 8 weeks after 12.5 minutes of global ischemia in rat brain. Following neuronal loss of 30-40% in central and dorsolateral striatum at day 3, neuronal damage in the substantia nigra (SN) was assessed at 4-8 weeks using immunohistochemistry for glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), and calretinin (CR). At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)-significantly decreased. CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01). Movement coordination was impaired at day 56, as evaluated using beam-walking test (time-to-traverse 5.6 ± 1.2 sec versus 11.8 ± 5.4 sec; sham versus ischemia, p < .05, n = 5, and 7, resp.). Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.


Anaesthesia for emergency caesarean section in a patient with large anterior mediastinal tumour presenting as intrathoracic airway compression and superior vena cava obstruction. Anterior mediastinal mass is an uncommon pathology that presents significant anaesthetic challenges because of cardiopulmonary compromise. We present a case that presented in the third trimester of pregnancy with severe breathlessness, orthopnoea, and symptoms of superior vena cava obstruction. The patient had emergency Caesarean section under epidural anaesthesia with a good outcome. The paper discusses the relevant perioperative considerations for this complex scenario and reviews reports of similar conditions.


Pathobiologic markers of the ewing sarcoma family of tumors: state of the art and prediction of behaviour. Over the past three decades, the outcome of Ewing sarcoma family tumor (ESFT) patients who are nonmetastatic at presentation has improved considerably. The prognosis of patients with metastatic disease at the time of diagnosis and recurrence after therapy remains dismal. Drug-resistant disease at diagnosis or at relapse remains a major cause of mortality among patients diagnosed with ESFT. In order to improve the outcome for patients with potential relapse, there is an urgent need to find reliable markers that either predict tumor behaviour at diagnosis or identify therapeutic molecular targets at the time of recurrence. An improved understanding of the cell of origin and the molecular pathways that regulate tumorigenicity in ESFT should aid us in the search for novel therapies for ESFT. The purpose of this paper is thus to outline current concepts of sarcomagenesis in ESFT and to discuss ESFT patterns of differentiation and molecular markers that might affect prognosis or direct future therapeutic development.


Porcine cysticercosis and risk factors in the gambia and senegal. During a stratified cross-sectional survey, 1705 pigs were sampled from 279 randomly selected households, 63 randomly selected communities and villages, from four study areas in The Gambia and Senegal during the period October 2007 to January 2008. Porcine cysticercosis prevalence detected by tongue inspection at animal level per study area ranged from 0.1% to 1.0%. Using an antigen-detection ELISA the seroprevalence of cysticercosis at both community/village and animal levels for the four selected study areas is: Western region 80.0% (95%CI: 52.4%-93.6%) and 4.8% (95%CI: 3.4%-6.5%), Bignona 86.7% (95%CI: 59.8%-96.6%) and 8.9% (95%CI: 5.0%-15.5%), Kolda 82.4% (95%CI: 46.8%-96.1%) and 13.2% (95%CI: 10.8%-16.0%), and Ziguinchor 81.3% (95%CI: 43.5%-96.1%) and 6.4% (95%CI: 4.0%-10.1%), respectively. No risk factors for cysticercosis were found significant in this study. This study proved that porcine cysticercosis is endemic and distributed widely in the study areas though its incidence might be suppressed by the generalised use of toilets and latrines in the study areas.


Promoter Polymorphism of RGS2 Gene Is Associated with Change of Blood Pressure in Subjects with Antihypertensive Treatment: The Azelnidipine and Temocapril in Hypertensive Patients with Type 2 Diabetes Study. We performed a prospective study to examine the genetic effect on the response to a calcium (Ca) channel blocker, azelnidipine and an ACE inhibitor, temocapril treatment in patients with hypertension, as a part of the prior clinical trial, the Azelnidipine and Temocapril in Hypertensive Patients with Type 2 Diabetes Study (ATTEST). Methods and Results. All subjects who gave informed consent for genetic research were divided into two groups: the subjects treated with azelnidipine or temocapril, for 52 weeks. We selected 18 susceptible genes for hypertension and determined their genotypes using TaqMan PCR method. RNA samples were extracted from peripheral blood, and quantitative real time PCR for all genes was performed using TaqMan method. One of the polymorphisms of the RGS2 gene was extracted as being able to influence the effect of these treatments to reduce BP. At eight weeks, BP change showed a significant interaction between the A-638G polymorphism of Regulator of G protein signaling-2 (RGS2) gene and treatment with azelnidipine or temocapril. There was no gene whose expression was associated with BP phenotypes or the polymorphisms of each gene. Conclusions. A-638G polymorphism of the RGS-2 gene could be a predictive factor for therapeutic performance of Ca channel blockers.


Lung cancer risk and genetic polymorphisms in DNA repair pathways: a meta-analysis. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. We conducted a meta-analysis of epidemiologic studies on the association between genetic polymorphisms in both base excision repair and nucleotide excision repair pathways, and lung cancer. We found xeroderma pigmentosum complementation group A (XPA) G23A (odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.61-0.94), 8-oxoguanine DNA glycosylase 1 (OGG1) Ser326Cys (OR = 1.22, 95% CI = 1.02-1.45), and excision repair cross-complementing group 2 (ERCC2) Lys751Gln (OR = 1.27, 95% CI = 1.10-1.46) polymorphisms were associated with lung cancer risk. Considering the data available, it can be conjectured that if there is any risk association between a single SNP and lung cancer, the risk fluctuation will probably be minimal. Advances in the identification of new polymorphisms and in high-throughput genotyping techniques will facilitate the analysis of multiple genes in multiple DNA repair pathways. Therefore, it is likely that the defining feature of future epidemiologic studies will be the simultaneous analysis of large samples of cases and controls.


Maxillofacial materials reinforced with various concentrations of polyhedral silsesquioxanes. This study evaluates two mechanical properties, tensile strength and tear strength, of maxillofacial materials reinforced with functional polyhedral silsesquioxane (POSS) nanoparticles at 0.0, 0.5, 1.0, 2.0, and 5.0% (mass/mass) loading. Adding POSS was found to significantly affect the overall tensile strength and extensibility of the maxillofacial material. Significant differences were found in mean peak load (p = .050) and extension before failure (p = .050), respectively, between concentrations of 0% and 5%. For tear resistance, a significant difference was observed in mean load (p = .002) between concentrations of 1% and 5%. Significant differences were also observed in extension before failure between concentrations of 0% and 1% (p = .002) and between 0% and 2% (p = .002). Increased resistance to tensile or shearing stresses could lead to greater clinical longevity. The following results suggest that functional nanoparticles can be used to improve properties without compromising clinical handling.