Naive CD4+ cells from cord blood can generate competent Th effector cells.
Umbilical cord blood (UCB) cells have been increasingly used as a source of hematopoietic stem cells for allogeneic transplantation. Previous reports suggest that the low risk of graft-versus-host disease in patients that received cord blood cells seems related to the distinctive nature of cord blood T cells. To analyze the maturation of CD4+CD45RA+ cord blood cells, we performed an in vitro differentiation assay to compare the generation of Th effector cells strictly from UCB and adult peripheral blood (APB) CD4+CD45RA+ cells. During the maturation into effector cells, UCB and APB cells acquired a comparable activation level determined by the expression pattern of CD69, CD40L, OX40 and CD62L as well as PD1 and CTLA-4 molecules. Moreover, the expression of CD45RO isoform was induced in most activated effector cells from both UCB and APB. OKT3-restimulated effector cells generated from naive UCB expressed higher levels of CD25 coinciding with the secretion of higher amounts of IL-2. Effector cells from both origins consisted of heterogeneous populations with similar frequencies of Th1 and Th2 cytokine producing cells, secreting equivalent levels of IL-4, IL-5 and IFNgamma. Although, higher levels of IL-10 were detected in the cytokine mRNA profile and in the supernatants of OKT3-restimulated UCB effector cells, blocking endogenous IL-10 with anti-IL-10 mAbs enhanced significantly the proliferative response of UCB as well as APB effector cells (P < 0.05). These results indicated that Th effector cells generated from naive UCB cells were intrinsically as competent as naive APB to respond to TCR-mediated stimulation. In addition, UCB effector cells produced higher IL-10 but its inhibitory effect on proliferation may be partially compensated by the higher production of IL-2 and enhanced expression of CD25.


Phylogenetic relationships and ancestral areas of the bustards (Gruiformes: Otididae), inferred from mitochondrial DNA and nuclear intron sequences.
The taxonomy of the bustards is poorly understood phylogenetically and has not been extensively evaluated using molecular methods. We sequenced part of the mitochondrial cytochrome b gene, the control region (central domain II), and an intron-exon crossing fragment of the nuclear chromo-helicase-DNA binding gene (CHD1) in 27 bustard taxa (including multiple subspecies) representing 11 genera and four gruiform outgroup species. Molecular datings suggest a Miocene origin for the family. Inferred phylogenetic relationships include the following: (i) the basal polytomy consists of 10 branches (mostly consistent with traditional genera), suggesting a rapid early radiation; (ii) sister relationships between several couplets of genera include Ardeotis with Neotis, Afrotis with Eupodotis (excluding E. rueppellii), Otis with Chlamydotis, and Houbaropsis with Sypheotides; (iii) the genus Eupodotis may be polyphyletic; and (iv) the currently delimited genera Ardeotis and Neotis do not form independent monophyletic lineages. Molecular evidence for the Afro-tropical origin of the Otididae is provided.


Effect of IL-18 on IL-1beta and sIL-1RII production by human neutrophils.
In the present study we investigated the effect of interleukin 18 (IL-18) on the production of IL-1beta and soluble IL-1 receptor II (sIL-1RII) by human neutrophils. The results obtained indicate that recombinant human IL-18 (rhIL-18) induces IL-1beta and, to a lesser extent, sIL-1RII production by human neutrophil isolated from peripheral blood. However, this effect was less important than lipopolysaccharide (LPS) stimulation. Additionally, our observations suggest that IL-18 can induce priming of neutrophils for IL-1beta and, to a lesser extent, sIL-IRII production by LPS-stimulated cells. The ability of IL-18 to serve as an effective modulator for IL-1beta and its regulatory protein may have significance in the inflammatory and immune reactions mediated by IL-1beta.


Compromised Sexual Health Among Male Patients With Implantable Cardioverter Defibrillator: A Cross-Sectional Questionnaire Study.
In cardiac patients with implantable cardioverter defibrillator (ICD), sexual function is sparsely described. To determine the prevalence and distribution of sexual dysfunction, and to describe whether primary or secondary prophylactic ICD indication and antitachycardia pacing (ATP) or shock is associated with sexual function. A cross-sectional survey of men with an implanted ICD was conducted at 2 university hospitals in Denmark. Inclusion criteria were men over the age of 18 with an ICD. Exclusion criterion was no partner. Sexual function was assessed by the International Index of Erectile Function questionnaire and data on implantation indication (primary/secondary prevention) and therapy such as ATP and shock (both appropriate and inappropriate) was obtained from the Danish ICD Register. Data from 415 questionnaires were analyzed (response rate 50.2%). Patients had a mean age of 63.9±12.1 years. Erectile dysfunction (ED) was present in 70% of patients, orgasmic dysfunction was present in 57.9% of patients, 82.8% had reduced sexual desire, 85.8% had intercourse satisfaction problems, and 76.9% experienced overall satisfaction problems (non-validated metric except for ED). Patients with an ICD on primary prophylactic indication had more sexual dysfunction and ED compared with patients with an ICD on secondary prophylactic indication. ATP therapy, but not shock, was associated with more ED. Sexual dysfunction is common in patients with ICD and is not limited to ED, but also orgasmic function, desire, intercourse, and overall satisfaction are affected. Primary prophylactic ICD indication and ATP, but not shock therapy, is associated with compromised sexual function. Palm P, Zwisler A-D, Svendsen JH. Compromised Sexual Health Among Male Patients With Implantable Cardioverter Defibrillator: A Cross-Sectional Questionnaire Study. Sex Med 2019;7:169-176.


Comparison of mothers and grandmothers physical and mental health and functioning within 6 months after child NICU/PICU death.
Losing a child is devastating for parents and grandparents. Family and friends generally focus on comforting and supporting the bereaved parents, unintentionally ignoring the bereaved grandparents. Grandmothers and grandfathers often struggle with wanting to help their adult children (deceased child's parents) without usurping the parents' responsibilities and decisions regarding the deceased child. Research on mothers' and grandmothers' health at about the same time after the same child's death in the neonatal or pediatric intensive care unit is lacking. The aim of this study was to compare mothers and grandmothers on physical health, mental health, and functioning in the first 1-6 months after the same child's death in a neonatal or pediatric intensive care unit. This cross-sectional secondary analysis compared 32 mothers with 32 grandmothers of the same 32 deceased children (newborn-6 years). Grandmothers were recruited through these 32 mothers. Most grandmothers and mothers were Hispanic (25%, 34%) or Black (44%, 41%), respectively. Mothers and grandmothers separately completed questions about their Physical Health, Mental Health [depression (Beck Depression Inventory), Post-Traumatic Stress Disorder (PTSD, Impact of Events-R), grief (Hogan Grief Reaction Checklist)], and Functioning (social support [MSPSS] and Employment) since the child's/grandchild's death. Paired t-tests and Chi Square tests were used to compare grandmothers with mothers of the same deceased infant/child on their private and separate responses to study measures. Mothers had significantly more acute illnesses than grandmothers. More mothers (63%) than grandmothers (37%) were categorized as clinically depressed. More mothers (69%) than grandmothers (44%) had clinical PTSD. Mothers reported significantly higher levels of despair and detachment than grandmothers. Only 4 mothers and 2 grandmothers were in therapy at the time of interview. Grandmothers and mothers rated their ability to concentrate on their work and their level of social support similarly. Mothers had more acute illnesses, more severe depression, and a higher level of grief than grandmothers. However, few received therapy despite their high levels of depressive and PTSD symptoms.


A Study of the Use of Psychopharmacologic Agents by Acutely Medically Ill Older Adults.
This retrospective study sought to investigate issues related to the safety of psychopharmacological agents used by acutely medically ill hospitalized older adults. It explored if there were any associations between commonly prescribed psychiatric medications that medically ill hospitalized older adults received and adverse events. It also sought to compare the safety of antidepressants, sedative/hypnotics, and antipsychotics, when used as a standing (on a preset schedule) and as needed pro re nata (PRN) basis. The study found that psychopharmacological agents are frequently prescribed for medically ill hospitalized older adults. No statistically significant difference was found as far as safety was concerned. The number of PRN medications that were used, and the total number of medications was associated with increased risk of transfer within the hospital to a higher level of care or transfer upon discharge to long-term-care/rehabilitation or hospice. Overall, the use of psychopharmacological agents did not appear to be related to serious adverse events.


Supplemental oxygen reduces the incidence of postoperative nausea and vomiting.
Postoperative nausea and vomiting (PONV) are unpleasent for patients and increase the risk of aspiration pneumonia. PONV is the leading cause of unexpected admission following planned day surgery. Despite new anaesthetic drugs and antiemetics, the incidence of PONV remains high. The incidence of PONV depends numerous factors including age, gender, obesity, anxiety, gastroparesis, history of motion sickness, previous PONV, and the duration and type of surgery. Anaesthesia related factors include premedication, ventilation techniques, and postoperative pain management. Recently, the intraoperative inspired oxygen concentration was identified as a factor that influences PONV. Among the three studies that evaluated intraoperative supplemental O2 for prevention of PONV, two found that it halves PONV while the third failed to identify any benefit. Since supplemental O2 is inexpensive and essentially risk-free, it appears preferable to pharmacologic anti-emetics for prevention of PONV in abdominal surgery.


A Bayesian generalized log-normal model to dynamically evaluate the distribution of pesticide residues in soil associated with population health risks.
Exploring better models for evaluating the distribution of pesticide residues in soil and sediment is necessary to assess and avoid population health risk. Frequentist philosophy and probability are widely used in many studies to apply a log-normal distribution associated with the maximum likelihood estimation, which assumes fixed parameters and relies on a large sample size for long-run frequency. However, frequentist probability might not be suitable for analyzing pesticide residue distribution, whose parameters are affected by many complex factors and should be treated as unfixed. This study aimed to implement a Bayesian generalized log-normal (GLN) model to better understand the distribution of pesticide residues in soil and quantify population risks. The Bayesian GLN model, including location, scale, and shape parameters, was applied for the first time to dynamically evaluate pesticide residue distribution in soil and sediments. In addition, a comprehensive human health risk assessment of exposure to lindane via soil was conducted using the lifetime cancer risk for carcinogenic effect, margin of exposure for non-carcinogenic effect, and disability-adjusted life year for health damage. The Bayesian posterior analysis results indicated that the distribution of the concentration of some pesticide was better fitted to a log-Laplace (e.g., the mode value of shape parameter for lindane is 1.079) or showed mixtures of distributions within the family of log-normal distributions (e.g., the mode value of shape parameter for p,p'-DDE is 2.395), which can better explain the long-tail phenomenon of pesticide residue distribution and dynamically evaluate distribution models. For lindane, the 95% uncertainty bounds on the 95th percentile computed from 95% highest probability density regions (credible intervals) of three parameters by using the Bayesian p-box method were [2.063, 1558.609] ng/g, which is several orders of magnitude larger than the computed frequentist 95% confidence interval of [4.690, 8.095] ng/g and indicates that the population could have cancer risk concerns. These uncertainty analysis results from the Bayesian GLN approach indicated a larger variation of Lindane soil residues, which might reflect the complex and unpredictable mechanism of pesticide residue distribution including both unfixed models and distribution parameters. In summary, Bayesian GLN model is more flexible for the dynamic evaluation of pesticide soil residue distribution, retains posteriors for future data analysis, and could better quantify the uncertainties in population health risks. Therefore, this study can provide a novel and dynamical perspective of pesticide residue distribution and help better quantify health risks.


Influence of Nanoclay Dispersion Methods on the Mechanical Behavior of E-Glass/Epoxy Nanocomposites.
Common dispersion methods such as ultrasonic sonication, planetary centrifugal mixing and magnetic dispersion have been used extensively to achieve moderate exfoliation of nanoparticles in polymer matrix. In this study, the effect of adding three roll milling to these three dispersion methods for nanoclay dispersion into epoxy matrix was investigated. A combination of each of these mixing methods with three roll milling showed varying results relative to the unmodified polymer laminate. A significant exfoliation of the nanoparticles in the polymer structure was obtained by dispersing the nanoclay combining three roll milling to magnetic and planetary centrifugal mixing methods. This exfoliation promoted a stronger interfacial bond between the matrix and the fiber, which increased the final properties of the E-glass/epoxy nanocomposite. However, a combination of ultrasound sonication and three roll milling on the other hand, resulted in poor clay exfoliation; the sonication process degraded the polymer network, which adversely affected the nanocomposite final properties relative to the unmodified E-glass/epoxy polymer.


Effects of the neonatal sex steroid environment on growth hormone-releasing hormone and somatostatin gene expression.
The growth hormone (GH) secretory pattern changes significantly throughout development in both male and female rats, becoming markedly sexually dimorphic after pubertal onset. This observation suggests that pubertal sex steroids play a role in the manifestation of this phenomenon. The neonatal steroid environment has also been shown to be intricately involved in the generation of the final adult GH secretory pattern, but the mechanisms underlying this effect remain unknown. We have addressed the question as to whether the developmental changes in the GH secretory pattern are correlated with changes in the hypothalamic neuropeptides that regulate its release from the anterior pituitary, i.e., somatostatin (SS) and growth hormone-releasing hormone (GHRH). The effects of neonatal testosterone and adult testosterone treatments on these two neuropeptide systems have also been studied. We have found that the synthetic capacity, as reflected in relative messenger RNA (mRNA) levels, of both SS and GHRH neurons changes throughout development in both male and female rats. These mRNA levels are also sexually dimorphic at certain times during maturation and, at least in the adult male, can be modulated by changes in testosterone levels. In support of the hypothesis that sex steroids play a role in the organization of the developing hypothalamus, we have shown that both estradiol and testosterone promote the survival of hypothalamic neurons in vitro. Preliminary in vivo studies indicate that the neonatal sex steroid environment may influence the number of GHRH neurons that are found in the adult brain, as well as their sensitivity to adult steroids.(ABSTRACT TRUNCATED AT 250 WORDS)


Immobilization hypercalcaemia in patients on regular haemodialysis.
Immobilization of normal people causes reabsorption of calcium from bone, a small rise in serum ionized calcium, and, rarely, frank hypercalcaemia. The hazard is increased when patients with renal osteodystrophy are immobilized because of pathological fractures.


Modulation of Surface-Catalyzed Secondary Nucleation during Amyloid Fibrillation of Hen Egg White Lysozyme by Two Common Surfactants.
Amyloid fibrillation by hen egg white lysozyme (HEWL) under the influences of two common surfactants, sodium dodecyl sulfate (SDS) and Triton X-100 (TX-100), was investigated with atomic force microscopy (AFM) and Fourier transform infrared (FTIR) spectroscopy. Detailed AFM investigations indicated that both SDS and TX-100 were able to induce some significant morphological changes of HEWL amyloid fibrils. Both SDS and TX-100 could induce a morphological change which was characterized with alternating fibril regions with increased thicknesses along the fibril axis. In addition, TX-100 was also able to induce a morphological change which was characterized with fibril branching. In contrast, the positively charged cetyltrimethylammonium bromide displayed no such effect as compared with the negatively charged SDS and the nonionic TX-100. These intriguing modulation effects of SDS and TX-100 on amyloid fibrillation were hypothesized to be due to surfactant-induced surface-catalyzed secondary nucleation owing to the noncovalent interaction between the surfactants and HEWL. The proposed hypothesis was further supported by FTIR spectroscopic investigation, which demonstrated the formation of a SDS-amyloid fibril complex and TX-100-amyloid fibril complex. Detailed FTIR analysis suggested that the tail group of SDS associated with amyloid fibrils is more disordered similar to that of SDS in aqueous solution, while the headgroup of SDS appears to interact with amyloid fibrils strongly similar to that of SDS in the solid state, and the ether groups of TX-100 associated with amyloid fibrils experienced a different microenvironment as compared with that of neat TX-100. Additional control experiments with FTIR spectroscopy revealed that the interactions of SDS/TX-100 with HEWL amyloid fibrils were different from those of SDS/TX-100 with HEWL amorphous aggregates. In addition, the β-sheet structures of the HEWL amyloid fibrils were found to be increased due to the influences of SDS and TX-100. Our work provides new insight into the modulation effects of surfactants on amyloid fibrillation.


Carbonic anhydrase VI in the mouse nasal gland.
Western blotting analysis of mouse nasal tissue using a specific anti-mouse secreted carbonic anhydrase (CA VI) antibody has shown that CA VI is present in this tissue. A single immunoreactive band of 42 kD was observed, as has been found previously for salivary tissues. RT-PCR analysis has shown that nasal mucosa expressed CA VI mRNA. By immunohistochemistry (IHC), CA VI was observed in acinar cells, in duct contents of the anterior gland of the nasal septum, and in the lateral nasal gland. The Bowman's gland, the posterior gland of the nasal septum, and the maxillary sinus gland were negative. Immunoreactivity was also observed in the mucus covering the respiratory and olfactory mucosa and in the lumen of the nasolacrimal duct. In contrast, an anti-rat CA II antibody (that crossreacts with the mouse enzyme) stained only known CA II-positive cells and an occasional olfactory receptor neuron. These results indicate that CA VI is produced by the nasal gland and is secreted over the nasal mucosa. By reversible hydration of CO(2), CA VI is presumed to play a role in mucosal functions such as CO(2) sensation and acid-base balance. It may also play a role in olfactory function as a growth factor in maturation of the olfactory epithelial cells.


Functional expression of H1-histaminergic receptors in Xenopus laevis oocytes injected with bovine adrenal medullary mRNA.
We prepared poly (A)+ mRNA from bovine adrenal medulla and electrophysiologically examined the expression of H1-histaminergic receptors in Xenopus laevis oocytes. Histamine dose-dependently induced inward currents in oocytes injected with the mRNA, but not in those injected with water or the non-injected oocytes. This response was also induced by H1-agonists and antagonized by H1-antagonists, while both an H2-agonist and an antagonist had no effect. These results clearly demonstrate that H1-histaminergic receptors are functionally expressed in oocytes injected with exogenous mRNA.


Cancer Immunotherapy: Silencing Intracellular Negative Immune Regulators of Dendritic Cells.
Dendritic cells (DCs) are capable of activating adaptive immune responses, or inducing immune suppression or tolerance. In the tumor microenvironment, the function of DCs is polarized into immune suppression that attenuates the effect of T cells, promoting differentiation of regulatory T cells and supporting tumor progression. Therefore, blocking negative immune regulators in DCs is considered a strategy of cancer immunotherapy. Antibodies can target molecules on the cell surface, but not intracellular molecules of DCs. The delivery of short-hairpin RNAs (shRNA) and small-interfering RNAs (siRNA) should be a strategy to silence specific intracellular targets in DCs. This review provides an overview of the known negative immune regulators of DCs. Moreover, a combination of shRNA/siRNA and DC vaccines, DNA vaccines in animal models, and clinical trials are also discussed.


Retroperitoneal germ cell tumors: a clinical study of 12 patients.
The aim of the study was to examine the clinical presentation, method(s) of treatment, complications, and results in newborns and infants with retroperitoneal germ cell tumors (GCTs). A retrospective chart review of all patients treated between 1974 and 2002 for GCT located in the retroperitoneum in 2 institutions identified 12 patients with histologically proven retroperitoneal GCT. Vital data concerning pregnancy and delivery were analyzed. Age at diagnosis and symptoms were recorded, as well as possibly associated anomalies. Data concerning surgical treatment, perioperative and postoperative complications, histological staging, and final outcome were all analyzed. In 3 patients, the diagnosis had been made antenatally between 31 and 35 weeks of gestation. In 1 patient, the diagnosis was made at birth, and in 8 later in life (ages 3, 5, 7, 8, 8, 11, 18, and 24 months). Symptoms in these 8 boys and 4 girls were abdominal distension and a palpable upper abdominal mass, right-sided in 5, left-sided in 5, and central in 2; the tumor was usually big. Associated anomalies were noted in 4 patients and were chromosomal in 3 (Down syndrome in 2 and Klinefelter syndrome in 1). One baby died of uncontrollable bleeding during an emergency operation immediately after traumatic birth. The other 11 infants survived. Four other patients showed serious perioperative complications (1 caval vein tear, 1 choledochal tear, 1 cyst rupture, and 1 esophagogastric tear) which were managed without further consequences. Histologically, 4 tumors were mature teratomas, 6 were immature teratomas (grade I in 4, grade II in 1, and grade II-III in 1), and 2 were malignant yolk sac tumors (YSTs). The patients with YSTs underwent surgical biopsy, followed by chemotherapy and excision of the remaining tumor and of the metastases. No adjuvant treatment was administered in the patients with benign disease. Nine survivors with benign tumor are disease-free between 1 and 30 years after surgery. Two patients with YST have now been in remission for 6 and 5 years, respectively. Both this study and the literature review performed testify to the extreme rarity of GCTs in the retroperitoneum. Surgical removal of the tumors appeared to be hazardous because of the extent of the tumor, the displacement and elongation of adjacent structures and organs, and/or the adhesion of the tumor to surrounding tissues; this resulted in several perioperative complications. The long-term results are good, however, with 9 of 10 patients with benign tumors in good health after a mean follow-up of 12 years, and with the 2 patients with YST in remission for 6 and 5 years, respectively.


Autoimmune disease and silicone breast implants.
An association between crystalline silica and immune disease has long been recognized. However, despite ongoing case reports of systemic autoimmune disease in silicone implant recipients, the available data has not been sufficient to prove or disprove a causal relationship. Silicone has been shown to "bleed" from the implants and can migrate to distant sites. There is evidence of cellular and humoral immune responses to silicone in vivo, but the role of these responses in the development of connective tissue disorders has not been determined. Further studies are necessary to elucidate the role of silicone, if any, in the pathogenesis of autoimmune connective tissue disease. Meanwhile, the implant population needs to be closely monitored; their clinical management should be based on a case by case evaluation.


DNA damage, cellular senescence and organismal ageing: causal or correlative?
Cellular senescence has long been used as a cellular model for understanding mechanisms underlying the ageing process. Compelling evidence obtained in recent years demonstrate that DNA damage is a common mediator for both replicative senescence, which is triggered by telomere shortening, and premature cellular senescence induced by various stressors such as oncogenic stress and oxidative stress. Extensive observations suggest that DNA damage accumulates with age and that this may be due to an increase in production of reactive oxygen species (ROS) and a decline in DNA repair capacity with age. Mutation or disrupted expression of genes that increase DNA damage often result in premature ageing. In contrast, interventions that enhance resistance to oxidative stress and attenuate DNA damage contribute towards longevity. This evidence suggests that genomic instability plays a causative role in the ageing process. However, conflicting findings exist which indicate that ROS production and oxidative damage levels of macromolecules including DNA do not always correlate with lifespan in model animals. Here we review the recent advances in addressing the role of DNA damage in cellular senescence and organismal ageing.


On the nature and reduction of plaque-mimicking flow artifacts in black blood MRI of the carotid bifurcation.
Cardiac-gated black blood MRI of the carotid artery bifurcation in normal human subjects shows signal within the lumen suggesting wall thickening or atherosclerotic plaque. This signal was believed to be artifactual, arising from complex flow patterns present at the carotid bifurcation. Computer simulation of the hemodynamics and black blood multislice image acquisition in a model of the carotid bifurcation showed that these artifacts arise from spins recovering their signal within the slow, recirculating flow of the carotid bulb. The computed hemodynamics also suggested that these artifacts could be minimized or eliminated entirely by gating the acquisition of slices in the most artifact-prone region of the carotid bulb within a 250-ms window after peak systole. Application of these predictions to studies of normal volunteers showed that, in most cases, these flow artifacts in black blood MRI can be eliminated simply by altering the phase of the cardiac cycle to which the image acquisition is gated. The observation that the size and placement of the saturation slabs had little effect on these artifacts suggested that, in those cases in which recirculation persists throughout the cardiac cycle, either inversion-recovery or presaturation within the bulb itself would be required to suppress them.


Congenital perilymphatic fistula: a prospective study in infants and children.
A 3-year prospective study of 244 children (aged 5 months to 17 years) with sensorineural hearing loss of unknown cause revealed that 57 children (23%) had radiographic evidence of abnormalities of the temporal bone, detected by computed tomography scan, and/or progression of sensorineural hearing loss. Of these 57 children, 42 (74%) underwent surgical exploration, with 15 children (26%) of this subgroup demonstrating active congenital perilymphatic fistula. The prevalence of congenital perilymphatic fistula in a large, closely monitored population of children with unexplained sensorineural hearing loss appears to be at least 6% (15 of 244 children). The incidence may be higher because some congenital perilymphatic fistulae may leak intermittently and not be observed during middle ear surgery. Therefore, in children with suspected sensorineural hearing loss, early and frequent audiological evaluations should be made to rule out progressive/fluctuating sensorineural hearing loss. These children should also have radiographic imaging of their temporal bone by computed tomography scan. The use of both methods is the best indicator for congenital perilymphatic fistula.


Heterogeneity of colloidal particle networks analyzed by means of Minkowski functionals.
The heterogeneity and large scale connectivity of colloidal particle networks, which are generated by Brownian dynamics simulations, is examined. This is achieved by employing integral geometric measures in the form of the Minkowski functionals or quermassintegrals. It is found that these measures in conjunction with the parallel-body technique amount to a powerful tool to characterize the structure, going beyond the information contained in the pair-correlation function. The development of heterogeneities during network formation as well as their dependence on the volume fraction and the interaction potential is studied. In particular, it is found that slow coagulation enhances the heterogeneity of the network compared to fast coagulation.


MRI findings in movement disorders and associated sleep disturbances.
One of the most useful tools for identifying sleep disturbances is neuroimaging, especially magnetic resonance imaging (MRI). This review research was to look at the role of MRI findings in movement disorders and sleep disturbances. This review collects all MRI data on movement disorders and sleep disruptions. Between 2000 and 2022, PubMed and Google Scholar were utilized to find original English publications and reviews. According to the inclusion and exclusion criteria, around 100 publications were included. We only looked at research that explored MRI modality together with movement problems, sleep disorders, and brain area involvement. Most of the information focuses on movement irregularities and sleep interruptions. Movement disorders such as Parkinson's disease (PD), Huntington's disease (HD), neuromuscular diseases, rapid eye movement (REM) sleep behavior movement disorder (RBD), cerebellar movement disorders, and brainstem movement disorders are assessed using MRI-based neuroimaging techniques. Some of the brain areas were associated with disorders in movement abnormalities and related sleep disturbances. This review found that many people with mobility disorders also have sleep problems. Some brain areas' malfunctions may cause motor and sleep issues. Neuroimaging helps us understand the sleep difficulties associated with movement disorders by examining the structural and functional implications of movement disorders and sleep disturbances.


MS title: Catalytic oxidation and removal of arsenite in the presence of Fe ions and zero-valent Al metals.
Arsenic immobilization in acid mine drainage (AMD) is required prior to its discharge to safeguard aquatic organisms. Zero-valent aluminum (ZVAl) such as aluminum beverage cans (AlBC) was used to induce the oxidation of As(III) to As(V) and enhance the subsequent As removal from an artificially prepared AMD. While indiscernible As(III) oxidation was found in aerated ZVAl systems, the addition of 0.10-0.55mM Fe(II) or Fe(III) into the AMD significantly promoted the As(V) production. Reactions between Fe(II) and H2O2, which was produced through an oxidative reaction of ZVAl with dissolved oxygen, generated OH radicals. Such OH radicals subsequently induced the As(III) oxidation. Over the course of the Fenton like reaction, ZVAl not only directly generated the H2O2, but indirectly enhanced the OH radical production by replenishing Fe(II). Arsenite oxidation in the aerated ZVAl/Fe and AlBC/Fe systems followed zero- and first-order kinetics. Differences in the kinetic reactions of ZVAl and AlBC with respect to As(III) oxidation were attributed to higher productive efficiency of the oxidant in the AlBC systems. After the completion of As(III) oxidation, As(V) could be removed simultaneously with Al(III) and Fe(III) by increasing solution's pH to 6 to produce Al/Fe hydroxides as As(V) scavengers or to form Al/Fe/As co-precipitates.


Development of a de novo cerebral arteriovenous malformation in a child with sickle cell disease and moyamoya arteriopathy. Case report.
The authors report the unique case of a 6-year-old African-American girl with sickle cell disease (SCD) and an associated moyamoya arteriopathy who developed a de novo arteriovenous malformation (AVM) of the cerebral circulation. Based on preoperative cerebral angiography, computerized tomography angiography, and magnetic resonance imaging, the incidentally discovered lesion was originally thought to be a direct arteriovenous fistula with an associated varix. At surgery, however, a 1.5-cm AVM was identified adjacent to the deep surface of the varix, and it was successfully resected. The diagnosis of cerebral AVM was then confirmed histopathologically. Based on a review of the literature, no published correlation between cerebral AVMs and SCD exists. In addition to reporting this case, the authors provide a description of AVM pathogenesis, with particular emphasis on acquired AVMs of the cerebral circulation.


Time-based distribution of Staphylococcus saprophyticus pulsed field gel-electrophoresis clusters in community-acquired urinary tract infections.
The epidemiology of urinary tract infections (UTI) by Staphylococcus saprophyticus has not been fully characterised and strain typing methods have not been validated for this agent. To evaluate whether epidemiological relationships exist between clusters of pulsed field gel-electrophoresis (PFGE) genotypes of S. saprophyticus from community-acquired UTI, a cross-sectional surveillance study was conducted in the city of Rio de Janeiro, Brazil. In total, 32 (16%) female patients attending two walk-in clinics were culture-positive for S. saprophyticus. Five PFGE clusters were defined and evaluated against epidemiological data. The PFGE clusters were grouped in time, suggesting the existence of community point sources of S. saprophyticus. From these point sources, S. saprophyticus strains may spread among individuals.


Hospitalization due to drug use did not change after a decade of the Psychiatric Reform.
To investigate whether the psychiatric hospitalization rates due to use of psychoactive substances and average time of hospitalization suffered any changes after the first decade of effective implementation of the psychiatric reform in Brazil. This article examines the evolution of hospitalizations due to disorders arising from the use of alcohol or other substances in the state of Santa Catarina, Southern Brazil, from 2000 to 2012. This is an ecological, time-series study, which uses data from admissions obtained by the Informatics Service of the Brazilian Unified Health System. Hospitalization rates by 100,000 inhabitants and average time of occupancy of beds were estimated. Coefficients of variation of these rates were estimated by Poisson Regression. The total and male hospitalization rates did not vary (p = 0.056 and p = 0.244, respectively). We observed an increase of 3.0% for the female sex (p = 0.049). We did not observe any significant variation for occupancy time of beds. The deployment of services triggered by the Brazilian psychiatric reform was not accompanied by a reduction of hospitalization rates or mean occupancy time of hospitalized patients during this first decade of implementation of the reform.


Opinions of elderly people on treatment for end-stage renal disease.
As more people survive into old age, a greater number are becoming eligible for dialysis treatment for end-stage renal failure. In the UK the elderly have previously been excluded from treatment programmes, and continuing financial constraints are unlikely to improve this situation. There are few data on the views of elderly subjects on renal replacement treatment. We have, therefore, explored the views of elderly subjects in this study. 50 subjects were selected from hospital geriatric wards and nursing homes. A short clinical vignette about a 75-year-old patient with renal failure was presented, and the subjects were asked to give their opinion on choices made by the patient to different treatment options. The subjects were then asked what choice they would make if in the same situation. They were asked what level of symptoms they would tolerate and for their views on cost and treatment allocation. Important contributors to quality of life were also determined for each subject using visual analogue scales. 84% of the subjects would choose dialysis treatment, and 78% of all elderly would attend hospital as necessary, if their symptoms could be relieved. 54% of the in-patient elderly and 83.3% of nursing home elderly even when physically disabled and living in a nursing home would want dialysis for end-stage renal failure. 74% of all elderly preferred to have home dialysis treatment. Only 36% of the subjects thought cost was important when allocating dialysis to the elderly. Being independent and free from major symptoms was regarded as important for a good quality of life. In this survey, elderly subjects wanted dialysis treatment. Neither age nor cost were considered important determinants for resource allocation. Symptom relief and maintaining independence were considered the main goals of treatment.


Scyllo-inositol: Transverse relaxation time constant at 3 T and concentration changes associated with aging and alcohol use.
The goals of this study were to measure the apparent transverse relaxation time constant, T2 , of scyllo-inositol (sIns) in young and older healthy adults' brains and to investigate the effect of alcohol usage on sIns in young and older healthy adults' brains, using proton magnetic resonance spectroscopy (MRS) at 3 T. Twenty-nine young adults (age 21 ± 1 years) and 24 older adults (age 74 ± 3 years) participated in this study. MRS data were acquired from two brain regions (the occipital cortex and posterior cingulate cortex) at 3 T. The T2 of sIns was measured using a localization by adiabatic selective refocusing (LASER) sequence at various echo times, while the sIns concentrations were measured using a short-echo-time stimulated echo acquisition mode (STEAM) sequence. A trend towards lower T2 relaxation values of sIns in older adults was observed, although these were not significant. sIns concentration was higher with age in both brain regions and was significantly higher in the young when considering alcohol consumption of more than two drinks per week. This study shows that differences in sIns can be found in two distinct regions of the brain across two age groups, potentially reflecting normal aging. In addition, it is important to take into account alcohol consumption when reporting the sIns level in the brain.


Possibilities for preventive treatment in rheumatoid arthritis? Lessons from experimental animal models of arthritis: a systematic literature review and meta-analysis.
Current research in rheumatoid arthritis focuses on preclinical disease phases as it is hypothesised that early preclinical treatment might prevent progression to full-blown disease. Since performance of studies in prearthritis phases in humans is challenging, animal models offer an opportunity to evaluate preventive treatments. We performed a systematic literature review and summarised treatment effects during different stages of arthritis development in animal models. Eight medical literature databases were systematically searched. Studies were selected if they reported effects of synthetic or biological disease-modifying antirheumatic drugs in animal models of arthritis (collagen-induced arthritis and adjuvant-induced arthritis) on arthritis severity, as measured with arthritis severity scores, paw swelling or paw volume. Quality was assessed using an 11-item checklist. Study characteristics were extracted and effect sizes obtained in high-quality studies were summarised in meta-analyses. Studies were categorised into three groups: prophylactic (prior to generation of autoantibody response), prearthritis (after induction of autoantibody response) and therapeutic intervention (after arthritis development). Out of 1415 screened articles, 22 studies (including n=712 animals) were eligible of good quality and included in meta-analyses. Prophylactic (16 experiments, n=312 animals) and prearthritis treatment (9 experiments, n=156 animals) both were associated with a reduction of arthritis severity (p<0.001 and p=0.005, respectively). Stratified analyses for different antirheumatic drugs initiated in the prearthritis phase suggested higher efficacy of methotrexate than of anti-tumour necrosis factor. Data of experimental studies in animal models of arthritis suggest that prophylactic and prearthritis treatment strategies are effective and hint at differences in efficacy between antirheumatic drugs.


Chimeric receptors as a tool for luminescent measurement of biological activities of steroid hormones.
Some applications of chimeric cellular models are presented to study the biological activities of steroid hormones. We have used several chimeric constructs encoding the DNA binding domain of Gal4 yeast protein fused to the hormone binding domain of various steroid receptors (MR, PR, GR and ER). Interactions of these chimeric receptors with a 17-mer DNA sequence, specific for Gal-4, control expression of the firefly luciferase as a reporter gene. Stable transfected cell lines expressing the firefly luciferase under the control of different steroids were established and an efficient and easy sub-cloning was allowed with the help of an imaging system using a single-photon-counting camera. In the cell lines obtained, the bioluminescent response can be easily measured and thus used to measure specific biological activities of steroid agonists or antagonists. We observed that the responses are effector-concentration-dependent and their biological activities will be compared to those of native receptors.


[Aortic root replacement using an allograft for active infective endocarditis with periannular abscess: single center experience].
Results of aortic root replacement using an allograft for active infective endocarditis in the aortic position and periannular abscess were studied. Aortic root replacement using a cryopreserved aortic allograft was performed 13 times in 12 patients (9 men, 3 women, mean age 52.8 years) at Saitama Medical School. Allografts were obtained from the Tokyo University Tissue Bank. Infection affected the prosthetic valve in 6 patients and the native valve in 7. Causative organisms were Staphylococci in 7 patients, Streptococci in 2, and unknown in 4. New York Heart Association functional class was II in 2 patients, III in 3, and IV in 8. Six patients required inotropic support. Four were mechanically ventilated. Two were in a state of profound shock. Four had multiple organ failure. Surgery was conducted under hypothermic cardiopulmonary bypass and cardioplegic arrest. Allograft was sewn into place by monofilament continuous sutures. Carrel patch technique was used for coronary artery reconstruction. Five patients underwent concomitant procedures (replacement of the ascending aorta in 2 patients, coronary artery bypass grafting in 1, mitral valve repair in 1, pulmonary artery reconstruction in 1). Duration of surgery, cardiopulmonary bypass, and aortic clamping were 507 +/- 154, 307 +/- 111, and 189 +/- 49 min, respectively. Two patients required intraaortic balloon pumping, and one required percutaneous cardiopulmonary support. Two patients in a state of shock died(hospital mortality: 15.4%). Duration of mechanical ventilation was 2.9 +/- 3.7 days. Intensive care unit stay was 4.6 +/- 5.5 days, and hospital stay was 61 +/- 26 days. One patient died of cancer 18 months later. One patient required reoperation 11 months later. Including operative death cases, cumulative survival at 2 years was 66.5% and freedom from cardiac events was 72.7%. Aortic root replacement with an allograft yielded acceptable clinical results.


Involvement of a CrmA-insensitive ICE/Ced-3-like protease in ceramide-induced apoptosis.
Ceramide has emerged as a novel lipid mediator of tumor necrosis factor (TNF)-induced apoptosis. However, the signals involved in this response are unknown. The present study demonstrates that ceramide-induced internucleosomal DNA cleavage is temporally associated with proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) and protein kinase C (PKC) delta. Overexpression of baculovirus protein p35 blocked ceramide-induced DNA fragmentation and proteolytic activity, whereas overexpression of cowpox virus protein CrmA had no effect on these events. By contrast, TNF-induced DNA cleavage and proteolytic activity was inhibited by CrmA as well as p35. These results indicate that ceramide-induced apoptosis involves the activation of a CrmA-insensitive protease that is distinct from that induced by TNF.


Muxeres en Acción: The Power of Community Cultural Wealth in Latinas Organizing for Health Equity.
Community psychology, despite its commitment to social justice, is prone to engage in deficit-based perspectives that do not appropriately capture the strengths of Latinx communities. Given these limitations, we use a Community Cultural Wealth (CCW) (Yosso, 2005) framework to describe how muxeres, Latina women who identify as promotoras, madres, and mamás, leveraged their political power and culturally informed leadership to improve the health and well-being of their communities. We highlight instances from our fieldwork, witnessing the agency of muxeres en acción for health equity. We offer three case studies to describe how we approached our collaborations with three groups of muxeres situated in different geographic locations in the state of California. The first case study discusses how immigrant muxeres who identify as promotoras (e.g., health workers) in the Central Valley developed their research skills through a promotora model that allowed them to build the capacity to advocate for the well-being of their communities. The second example offers reflections from a Community-Based Participatory Action Research (CBPAR) project with a group of Mexican immigrant madres in a gentrified community in San José. Lastly, the third case study describes how a group of mamás in the East Side of Los Angeles addressed issues of educational inequities. Together, these case studies illustrate muxeres' advocacy for their health and well-being. Because women in general, and muxeres in particular, are considered gatekeepers of culture and tradition within their families, it is crucial that community psychologists ground their work in ethically and culturally appropriate frameworks that highlight the power of muxeres.


Venous ulceration, fibrinogen and fibrinolysis.
The effect of long and short-term venous hypertension upon lymph fibrinogen concentrations was studied in an attempt to explain the peri-capillary deposition of fibrin reported in patients with post-phlebitic syndromes. The clearance of radioactive fibrinogen/thrombin clots from the subcutaneous tissues of rats and human volunteers was also studied. Both long- and short-term venous hypertension were found to increase fibrinogen transport across the interstitial space by more than 600%. Not only was there evidence of fibrinolytic activity in the lymph but after long-term venous hypertension alpha 2 antiplasmin activity was also detectable. Skin biopsies from the venous hypertensive ankles showed deposition of interstitial fibrin. The clearance of radioactive fibrinogen/thrombin clots from the subcutaneous tissues of the rat was found to be delayed if the rats were given epsilon amino caproic acid but it could not be increased with stanozolol. In human subjects it was found that patients with lipodermatosclerosis had delayed clot clearance and retarded blood fibrinolytic activity when compared with normal volunteers and patients with uncomplicated varicose veins. The principle cause why tall men are more subject to ulcers than short men, Dr Young conceived to be then length of the column of blood in their veins; which by its pressure, renders the legs less able to recover when hurt by any violence.


Identifying Environmental and Social Factors Predisposing to Pathological Gambling Combining Standard Logistic Regression and Logic Learning Machine.
Identifying potential risk factors for problem gambling (PG) is of primary importance for planning preventive and therapeutic interventions. We illustrate a new approach based on the combination of standard logistic regression and an innovative method of supervised data mining (Logic Learning Machine or LLM). Data were taken from a pilot cross-sectional study to identify subjects with PG behaviour, assessed by two internationally validated scales (SOGS and Lie/Bet). Information was obtained from 251 gamblers recruited in six betting establishments. Data on socio-demographic characteristics, lifestyle and cognitive-related factors, and type, place and frequency of preferred gambling were obtained by a self-administered questionnaire. The following variables associated with PG were identified: instant gratification games, alcohol abuse, cognitive distortion, illegal behaviours and having started gambling with a relative or a friend. Furthermore, the combination of LLM and LR indicated the presence of two different types of PG, namely: (a) daily gamblers, more prone to illegal behaviour, with poor money management skills and who started gambling at an early age, and (b) non-daily gamblers, characterised by superstitious beliefs and a higher preference for immediate reward games. Finally, instant gratification games were strongly associated with the number of games usually played. Studies on gamblers habitually frequently betting shops are rare. The finding of different types of PG by habitual gamblers deserves further analysis in larger studies. Advanced data mining algorithms, like LLM, are powerful tools and potentially useful in identifying risk factors for PG.


Chromosome studies in couples with repeated spontaneous abortions.
Karyotypes were prepared from peripheral blood leukocytes in 77 couples in whom there was no apparent cause for recurrent spontaneous abortion. In addition to conventional staining, chromosomes were stained by the new technics for Q-, G-, or C-banding. Translocations were found in 5 of 154 persons (3.25% or 1:31 individuals). The frequency of translocations in the general adult population is 0.4% (1:255). Two translocations were apparent only with the new technics for banding. The incidence of chromosomal microanomalies was 7.79% (2.6% in the general population). Karyotyping of couples with recurrent abortion is recommended, with use of the new staining technics.


Monte Carlo analysis of uncertainty attached to microbial pollutant degradation rates.
Prediction of bioremediation performance relies on models of microbial activity that are typically fitted to few data, which can lead to large errors in parameter estimates and uncertain prediction of reaction rates and degradation times. This paper presents a Monte Carlo approach to propagate the uncertainty about model parameters and error component through the Michaelis-Menten equation, yielding a probability distribution for both pollutant degradation rate and time for cleanup to some prescribed level. The procedure is illustrated using data related to the degradation kinetics of halogenated hydrocarbons by Methylomicrobium album BG8. It is shown that the assumption of homoscedasticity of the error variance in the Michaelis-Menten model is usually inappropriate, and analytical expressions are derived to account for the dependence of the error variance on the concentration of substrate. Depending on the substrate, the addition of formate might have a significant impact on the expected degradation rates and times, and the proposed approach allows one to test statistically such an impact for various substrate concentrations.


Automated Classification and Removal of EEG Artifacts With SVM and Wavelet-ICA.
Brain electrical activity recordings by electroencephalography (EEG) are often contaminated with signal artifacts. Procedures for automated removal of EEG artifacts are frequently sought for clinical diagnostics and brain-computer interface applications. In recent years, a combination of independent component analysis (ICA) and discrete wavelet transform has been introduced as standard technique for EEG artifact removal. However, in performing the wavelet-ICA procedure, visual inspection or arbitrary thresholding may be required for identifying artifactual components in the EEG signal. We now propose a novel approach for identifying artifactual components separated by wavelet-ICA using a pretrained support vector machine (SVM). Our method presents a robust and extendable system that enables fully automated identification and removal of artifacts from EEG signals, without applying any arbitrary thresholding. Using test data contaminated by eye blink artifacts, we show that our method performed better in identifying artifactual components than did existing thresholding methods. Furthermore, wavelet-ICA in conjunction with SVM successfully removed target artifacts, while largely retaining the EEG source signals of interest. We propose a set of features including kurtosis, variance, Shannon's entropy, and range of amplitude as training and test data of SVM to identify eye blink artifacts in EEG signals. This combinatorial method is also extendable to accommodate multiple types of artifacts present in multichannel EEG. We envision future research to explore other descriptive features corresponding to other types of artifactual components.


Unravelling the regulatory structure of biochemical networks using stimulus response experiments and large-scale model selection.
To unravel the complex in vivo regulatory interdependences of biochemical networks, experiments with the living organism are absolutely necessary. Stimulus response experiments (SREs) have become increasingly popular in recent years. The response of metabolite concentrations from all major parts of the central metabolism is monitored over time by modem analytical methods, producing several thousand data points. SREs are applied to determine enzyme kinetic parameters and to find unknown enzyme regulatory mechanisms. Owing to the complex regulatory structure of metabolic networks and the amount of measured data, the evaluation of an SRE has to be extensively supported by modelling. If the enzyme regulatory mechanisms are part of the investigation, a large number of models with different enzyme kinetics have to be tested for their ability to reproduce the observed behaviour. In this contribution, a systematic model-building process for data-driven exploratory modelling is introduced with the aim of discovering essential features of the biological system. The process is based on data pre-processing, correlation-based hypothesis generation, automatic model family generation, large-scale model selection and statistical analysis of the best-fitting models followed by an extraction of common features. It is illustrated by the example of the aromatic amino acid synthesis pathway in Escherichia coli.


Structure-function relationships in rat brain stem subnucleus interpolaris. VIII. Cortical inputs.
1. Spinal trigeminal (SpV) subnucleus interpolaris (SpVi) receives inputs from trigeminal (V) first- and second-order neurons, monoamine-containing brain stem nuclei, and somatosensory cortex. Prior studies suggest that SpVi receptive-field (RF) properties cannot be predicted solely on the basis of primary afferent inputs. To assess the cortico-V projection and its role in SpVi RFs, anatomic and electrophysiological experiments were conducted. 2. Phaseolus vulgaris leucoagglutinin (PHA-L) or wheat-germ-agglutinized horseradish peroxidase (WGA-HRP) were used as anterograde tracers to study cortico-V axons in 24 normal adult rats. Injections into SI barrel cortex-labeled pyramidal fibers that decussated at all levels of the V brain stem complex, though crossing fibers were most numerous in the pyramidal decussation and pons. A small number of axons projected to ipsilateral V brain stem subnuclei. PHA-L-labeled pyramidal fibers did not give rise to collaterals in their descent through the pons and medulla. 3. Heaviest terminal labeling occurred contralaterally and in the maxillary portion of caudalis laminae III-V. Moderately dense reaction product was seen in ventral portions of all other contralateral V brain stem subnuclei, as well as in laminae I and II of caudalis. Subnucleus oralis contained the least amount of label contralateral to the injection site. Ipsilateral projections were weak and most dense in principalis. 4. Cortico-V projections were topographic between matching whisker representations. Axons most commonly had longitudinal orientations and stringy shapes. Terminal boutons occurred at the ends of short collateral branches. Many of these collaterals were derived from axons that ascended through caudal V brian stem subnuclei after crossing in the lower medulla. 5. Cortico-V labeling was heavier in septal regions between single whisker representations. This "honeycomb-like" termination pattern was most pronounced in contralateral caudalis and SpVi and ipsilateral principalis. 6. In 13 other adult rats, right SI cortex was aspirated followed by single-unit recordings in left SpVi under pentobarbital sodium anesthesia. In 9 of these, chronic effects were evaluated by recording the responses of 346 left SpVi cells 4-55 days after the lesion. In the remaining four rats, acute effects were analyzed by recording the responses of 190 SpVi cells on the day of the lesion.(ABSTRACT TRUNCATED AT 400 WORDS)


Growth and carcass composition of broilers fed sunflower oil and olive oil.
Sunflower and olive oils were fed at the same dietary inclusion levels to male broilers as a means of varying the dietary linoleic acid concentration while maintaining similar concentrations of total fat and total unsaturated fatty acids. The type of oil and the dietary supplementation level influenced growth rate, food utilisation and carcass composition. Birds grew faster and utilised food more efficiently when fed the sunflower oil and had higher concentrations of body fat. Increasing the level of supplementation with either oil decreased body fat content. The different responses to the two oils were not related to differences in dietary amino acid balance, ME: protein ratios or rates of food passage through the digestive tract.


Novel technologies in cfDNA analysis and potential utility in clinic.
The profiling of plasma cell-free DNA (cfDNA) is becoming a valuable tool rapidly for tumor diagnosis, monitoring and prognosis. Diverse plasma cfDNA technologies have been in routine or emerging use, including analyses of mutations, copy number alterations, gene fusions and DNA methylation. Recently, new technologies in cfDNA analysis have been developed in laboratories, and potentially reflect the status of epigenetic modification, the immune microenvironment and the microbiome in tumor tissues. In this review, the authors discuss the principles, methods and effects of the current cfDNA assays and provide an overview of studies that may inform clinical applications in the near future.


Highly Efficient Multiple-Anchored Fluorescent Probe for the Detection of Aniline Vapor Based on Synergistic Effect: Chemical Reaction and PET.
A multiple-anchored fluorescent probe ((((hexane-1,6-diylbis(2,7-bis(4-formyl)-phenyl)-9H-fluorine-9,9-diyl))-bis(hexane-6,1-diyl))-bis(9H-carbazole-9,3,6-triyl))-tetrakis(benzene-4,1-diyl))-tetraformyl-(8FP-2F) with eight aldehyde groups was designed and synthesized. The molecule has four branches and highly twisted structure. Furthermore, it tends to self-assemble into nanospheres, which is beneficial for gaseous analyte penetration and high fluorescence quantum efficiency. Among gaseous analytes, detection of aniline vapor is extraordinarily important in the control of environmental issues and human diseases. Herein, 8FP-2F was introduced to detect aniline vapor with distinguished sensitivity and selectivity via simple Schiff base reaction at room temperature. After exposure to saturate aniline vapor, the 89% fluorescence of 8FP-2F was quenched in 50 s and the detection limit was as low as 3 ppb. Further study showed the suitable HOMO/LUMO energy levels and matched orbital symmetry between probe and aniline molecules ensured chemical reaction and PET process work together. The synergistic effect resulted in a significant sensing performance and fluorescence quenching toward aniline vapor. Moreover, the multiple active sites structure of 8FP-2F means it could be applied for constructing many interesting structures and highly efficient organic optoelectronic functional materials.


["Wrapping therapy" for hepatocellular carcinomas with collateral feeders].
A new treatment method to intercept collaterals with silicone rubber sheeting, called "wrapping therapy", was used for 18 patients with advanced hepatocellular carcinomas having collateral feeders from other organs surrounding the liver. Chemoembolization in 17 of the 18 patients in whom it had been conducted more than once, had proven ineffective. Obvious collateral feeders (parasitic branches) to the tumors were recognized on hepatic angiograms in two-thirds of the patients. This procedure was followed by regional chemotherapy and/or chemoembolization. The 3- and 4-year survival rates of the patients after "wrapping therapy" were 54% and 54%, respectively. This therapy is worth using for hepatocellular carcinomas uncontrolled by arterial therapy because of development of collateral feeders.


Antimicrobial agents in urinary tract infections in patients with spinal cord injury.
Because of the rapid introduction and active marketing of newer antimicrobial agents for urinary tract infections, it is important to evaluate newer antibiotics critically. Critical evaluation should be based on published reports, spectrum of action, and, very importantly, cost. Newer agents should be compared with known effective agents on the basis of hospital antimicrobial sensitivity tests. Simple, uncomplicated urinary tract infections caused by community-acquired multiple drug-sensitive uropathogens can be treated with almost any currently available antimicrobial agent. In these situations, a low-morbidity, low-cost agent with limited dosage should be chosen. In general, a 3-day course of trimethoprim-sulfamethoxazole, nitrofurantoin, a first-generation cephalosporin, a penicillin agent, or in some cases a fluoroquinolone will be both medically and cost effective. For complicated urinary tract infections, more selectivity must be exercised in choosing an appropriate antibacterial agent. In these situations, it is necessary to initiate appropriate diagnostic studies to identify causes and to treat those complications appropriately. The choice of antibiotics must be based on culture results. Initial empiric treatment should be carried out with a broad-spectrum agent of low morbidity. In these complicated infections, fluoroquinolones may be effective with low expected morbidity.


Pharmacogenomics courses in pharmacy school curricula.
Aim: The appropriate use and integration of pharmacogenetic (PGx) testing will pivot on provider preparation and training. Pharmacists have been recognized as one of the key providers in the delivery of PGx testing and as such, professional organizations have recommended inclusion of PGx content in pharmacy curricula. Methods: We reviewed the curriculum of 132 US pharmacy schools for information about PGx courses. Results: A total of 70 core curriculum courses were identified. 55 (42%) pharmacy schools included at least one PGx course as part of the core curriculum, and ten (8%) schools that offered a PGx course elective. Conclusion: While many pharmacy schools have responded to the accreditation standards to include PGx, less than half of the schools have developed a standalone course.


Cost-effectiveness of dolutegravir/abacavir/lamivudine in HIV-1 treatment-Naive (TN) patients in France.
To evaluate the cost-effectiveness of an integrase inhibitor (INI), dolutegravir (DTG), in combination with abacavir (ABC)/lamivudine (3TC) in France, in treatment-naive (TN) HIV adult patients. The ARAMIS microsimulation Markov model, evaluates costs and effects of DTG vs. first-line ARVs options including INIs (raltegravir, elvitegravir/c), protease inhibitors (PIs) (darunavir/r, atazanavir/r, lopinavir/r), non-nucleoside reverse transcriptase inhibitors (efavirenz and rilpivirine). Efficacy and safety data were derived from phase III studies and network meta-analysis. Treatment algorithms were based on French guidelines and experts opinion. Costs included routine HIV and opportunistic infection care, and death. The model showed the fixed-dose combination DTG/ABC/3TC was more effective than all other recommended regimens: patients stayed longer on first-line, and lived longer and healthier. With the exception of EFV, DTG/ABC/3TC was more efficacious and less costly compared to all strategies. The cost per QALY gained (ICER) for DTG compared to EFV was €6,939. DTG/ABC/3TC was more efficacious and less costly compared to INIs and PIs in all deterministic sensitivity analyses. DTG/ABC/3TC was cost-effective in the management of HIV TN patients in France. These results are mainly explained by its lower price compared to other INIs and PIs, DTG's superior efficacy and high barrier to resistance.


Potential for Hospital Based Corneal Retreival in Hassan District Hospital.
In developing countries, corneal diseases are the second leading cause of blindness. This corneal blindness can be treated through corneal transplantation. Though the present infrastructure is strong enough to increase keratoplasty numbers at a required rate, India has largest corneal blind population in the world. So a constant supply of high quality donor corneal tissue is the key factor for reduction of prevalence of corneal blindness. Considering the magnitude of corneal blindness and shortage of donor cornea, there is a huge gap in the demand and supply. To study the potential for hospital based retrieval of donor corneal tissue in Hassan district hospital after analysing the indicated and contraindicated causes of deaths, so that hospital corneal retrieval program in Hassan district hospital can be planned. The cross-sectional, retrospective and record-based study included all hospital deaths with age group more than two years occurred during one year period (January 2014 to December 2014). Data regarding demographic profile, cause of death, treatment given and presence of any systemic diseases were collected. The causes of deaths which are contraindicated for the retrieval of corneas were analysed and noted. The contraindications were based on the NPCB guidelines for standard of eye banking in India 2009. Out of 855 deaths, number of deaths in males (565) was greater than females (290). Numbers of deaths were highest between 41-60 years age group (343). Deaths due to HIV, septicaemia, meningitis, encephalitis, disseminated malignancies were contraindicated for corneal retrieval. Corneas could be retrieved from 736 deaths out of 855. Potential for corneal retrieval in a period of one year in Hassan District hospital was 86%. Hospital corneal retrieval program has got a great potential to bridge the gap between the need for the cornea and actually collected corneas which will contribute enormously in eliminating corneal blindness. In present study there was 86% potential for corneal retrieval among the hospital deaths.


AGA Clinical Practice Update on the Role of Artificial Intelligence in Colon Polyp Diagnosis and Management: Commentary.
The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to review the available evidence and provide expert commentary on the current landscape of artificial intelligence in the evaluation and management of colorectal polyps. This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. This Expert Commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors who are experienced endoscopists with expertise in the field of artificial intelligence and colorectal polyps.


A proposal for a national health care identifier.
This paper describes a proposed standard for the creation of a national health care identifier being developed under the auspices of the ASTM. The standard includes the desired properties of such an identifier and a description of existing identifier schemes. It includes a proposed identifier scheme, descriptions of how the proposed scheme would function, and an evaluation of how well the proposed scheme meets the properties outlined in the standards document. This paper provides a partial summary of the material contained in the proposed standard.


The effect of organophosphorus compounds on serum pseudocholinesterase levels in a group of industrial workers.
This paper presents the findings of a study of serum pseudocholinesterase activity in a group of 36 industrial workers chronically exposed to organophosphorus (OP) compounds. The mean pseudocholinesterase level of the workers was significantly lower than that of 36 other workers without a history of similar exposure. Although there was a high incidence of clinical features suggestive of OP compound toxicity in the exposed workers, no significant correlation between serum pseudocholinesterase levels and clinical symptoms and signs was found. Six exposed workers, found to have low serum pseudocholinesterase levels, were transferred for 6 months to work areas which did not involve OP exposure, whereupon their levels rose significantly back to the normal range.


Evaluation of alpha-adrenoceptor agonistic activity of RDS-127 (2-di-n-propylamino-4,7-dimethoxyindane) in rabbit and rat aortae.
The alpha-adrenergic activity of a dopamine receptor agonist, 2-di-n-propylamino-4,7-dimethoxyindane (RDS-127), has been studied on isolated rabbit and rat aortic strips. In both tissues, RDS-127 produced concentration-dependent contractions and its potency was not significantly different from that of phenylephrine. RDS-127-induced contractions were antagonized competitively by both prazosin and phentolamine in rabbit aortic strips, but the antagonists were noncompetitive in rat aortic strips.


Transcriptional response of Rhodococcus aetherivorans I24 to polychlorinated biphenyl-contaminated sediments.
We used a microarray targeting 3,524 genes to assess the transcriptional response of the actinomycete Rhodococcus aetherivorans I24 in minimal medium supplemented with various substrates (e.g., PCBs) and in both PCB-contaminated and non-contaminated sediment slurries. Relative to the reference condition (minimal medium supplemented with glucose), 408 genes were upregulated in the various treatments. In medium and in sediment, PCBs elicited the upregulation of a common set of 100 genes, including gene-encoding chaperones (groEL), a superoxide dismutase (sodA), alkyl hydroperoxide reductase protein C (ahpC), and a catalase/peroxidase (katG). Analysis of the R. aetherivorans I24 genome sequence identified orthologs of many of the genes in the canonical biphenyl pathway, but very few of these genes were upregulated in response to PCBs or biphenyl. This study is one of the first to use microarrays to assess the transcriptional response of a soil bacterium to a pollutant under conditions that more closely resemble the natural environment. Our results indicate that the transcriptional response of R. aetherivorans I24 to PCBs, in both medium and sediment, is primarily directed towards reducing oxidative stress, rather than catabolism.


Protective effects of PGE2 on diet-induced acute pancreatitis in mice.
Prostaglandins have been noted to have a "protective" effect against gastrointestinal mucosal injury induced by a wide variety of agents although possible protective effects of prostaglandins on injury to other tissues have not been reported. We have tested the effect of prostaglandin E2 (PGE2) on acute experimental pancreatitis induced by feeding young female mice a choline-deficient ethionine-supplemented (CDE) diet for 24 hr. Administration of 0.05--0.20 microgram PGE2/g body wt 1 hr before and 4 hr after institution of the CDE diet lowered the mortality rate of diet-induced pancreatitis from 56% to 31%. Larger and smaller doses of PGE2 were without effect. Administration of PGE2 (0.10 microgram/g body weight) diminished the rise in in-vitro LDH discharge and the increase in "free" Cathepsin D activity which occur during diet-induced pancreatitis. Similarly, PGE2 (0.10 microgram/g body wt) diminished the magnitude of the increase in in-vitro protein discharge and the elevated concentrations of trypsinogen and chymotrypsinogen in pancreas fragments taken from mice given the CDE diet. These findings indicate the PGE2 has a protective effect against CDE diet-induced acute experimental pancreatitis. The Cathespin D and LDH changes noted during CDE diet-induced pancreatitis suggest that this diet may decrease membrane integrity and thus allow these enzymes to leak out of the lysosomes and acinar cell, respectively, during pancreatitis. Although the basis for the protective effect of PGE2 remains unclear, our observations suggest that the prostaglandin may act to reduce the alteration in membrane integrity which occurs during CDE-diet induced pancreatitis.


Dynamic properties of the tight junction barrier.
A principal role of tight junctions is to seal the apical intercellular space and limit paracellular flux of ions and molecules. Despite the fact that tight junctions form heavily cross-linked structures, functional studies have fostered the hypothesis that the tight junction barrier is dynamic and defined by opening and closing events. However, it has been impossible to directly measure tight junction barrier function with sufficient resolution to detect such events. Nevertheless, recent electrophysiological and sieving studies have provided tremendous insight into the presence of at least two pathways of trans-tight junction flux: a high-capacity ion-selective "pore" pathway and a low-capacity "leak" pathway that allows the passage of macromolecules. Furthermore, it is now known that the tight junction molecular structure is highly dynamic and that dynamics are correlated with barrier function. Taken together, these data support a dynamic model of tight junction conductance and suggest that regulation of tight junction openings and closings may provide sensitive means of barrier regulation.


Heart disease and associated risk factors among Hawaiians: culturally responsive strategies.
The incidence of heart disease is disproportionately large among the Hawaiian population. This article discusses the prevalence of heart disease and associated risk factors among Hawaiians and identifies barriers to health care, including accessibility and the acceptability of services to this population. Case examples are provided. Culturally responsive strategies to address these problems are described, and implications for social work are discussed.


Comparative analysis of two-component signal transduction systems of Bacillus cereus, Bacillus thuringiensis and Bacillus anthracis.
Members of the Bacillus cereus group are ubiquitously present in the environment and can adapt to a wide range of environmental fluctuations. In bacteria, these adaptive responses are generally mediated by two-component signal transduction systems (TCSs), which consist of a histidine kinase (HK) and its cognate response regulator (RR). With the use of in silico techniques, a complete set of HKs and RRs was recovered from eight completely sequenced B. cereus group genomes. By applying a bidirectional best-hits method combined with gene neighbourhood analysis, a footprint of these proteins was made. Around 40 HK-RR gene pairs were detected in each member of the B. cereus group. In addition, each member contained many HK and RR genes not encoded in pairs ("orphans"). Classification of HKs and RRs based on their enzymic domains together with the analysis of two neighbour-joining trees of these domains revealed putative interaction partners for most of the "orphans". Putative biological functions, including involvement in virulence and host-microbe interactions, were predicted for the B. cereus group HKs and RRs by comparing them with those of B. subtilis and other micro-organisms. Remarkably, B. anthracis appeared to lack specific HKs and RRs and was found to contain many truncated, putatively non-functional, HK and RR genes. It is hypothesized that specialization of B. anthracis as a pathogen could have reduced the range of environmental stimuli to which it is exposed. This may have rendered some of its TCSs obsolete, ultimately resulting in the deletion of some HK and RR genes.


[Hemostasis and ultrasonic shears for thyroid surgery].
Hemostasis and coagulation are vital during thyroidectomy. The gland is highly vascularised and any lack in the control of thyroid vessels has immediate consequence in terms of morbidity. General principles of coagulation are reminded and the use of ultrasonic dissector is presented as an attractive alternative. A comparative study performed in 2000 and more recent data confirm the advantage of the new device in terms of operative time saving.


Eating and body image disturbances in male-to-female and female-to-male transsexuals.
The aim of the study was to discover whether persons with Gender Identity Disorder (GID) differed from controls of both sexes and from persons with eating disorders in terms of the degree of eating and body image disturbance, self-esteem, and depression. A total of 88 self-identified male-to-female transsexuals (MtF), 43 female-to-male transsexuals (FtM), 62 females with an eating disorder, 56 male controls, and 116 female controls completed the Eating Disorder Examination Questionnaire, Eating Disorder Inventory, Body Checking Questionnaire, Drive for Muscularity Scale, Rosenberg Self-Esteem Scale, and Beck Depression Inventory. MtF showed higher scores on restrained eating, eating concerns, weight concerns, shape concerns, drive for thinness, bulimia, body dissatisfaction, and body checking compared to male controls, and concerning some variables also compared to female controls. FtM displayed a higher degree of restrained eating, weight concerns, shape concerns, body dissatisfaction, and body checking compared to male controls. Furthermore, participants with GID showed higher depression scores than did controls, whereas no differences concerning drive for muscularity and self-esteem were found. Between MtF and FtM, the only significant difference emerged for body checking, with MtF displaying higher scores. Although it was shown that on these variables the values for persons with GID were lower than for those with eating disorders, these data lead us to speculate that persons with GID might be at a higher risk of eating disturbances. Therefore, the implementation of prevention programs might help persons with GID to avoid developing a clinically relevant eating disorder.


Direct transition to long-acting risperidone--analysis of long-term efficacy.
This report presents data from the extension phase of a 6-month trial that evaluated the efficacy of risperidone long-acting injectable (RLAI) in stable psychotic patients requiring a treatment change. Patients continued to receive RLAI every 2 weeks for a maximum of 12 months from study entry. Symptoms were assessed using the PANSS after 1, 3, 6, 9 and 12 months of treatment (or treatment endpoint). Remission of severity criteria were defined as < or =3 points in all PANSS items suggested by the Remission in Schizophrenia Working Group.715 patients (63% male) entered the extension phase and 508 completed the 12-month study. The mean PANSS total score at Day 0 was 74.9+/-22.7. This was significantly reduced after 1 month (67.7 +/-22.3, p< or =0.001), with continued improvements over the 12 months of the study until treatment endpoint (59.7+/-21.9). Significant improvements from Day 0 to endpoint were also seen in the scores for all PANSS subscales and symptom factors. The proportion of patients who met the PANSS severity criteria for remission increased from 29% at Day 0 to 60% at endpoint, and the proportion of patients who met these criteria for < or = 6 months increased from 24% at Month 6 to 45% at endpoint. Treatment with RLAI for up to 12 months provided significant and sustained improvements in symptom control in patients with schizophrenia. These improvements may help patients to achieve and remain in remission.


Biliary inflammatory pseudotumor: imaging features in seven patients.
Hepatic biliary pseudotumor is a benign, rare, and poorly understood tumor that is typically diagnosed after aggressive surgical intervention. The purpose of this report is to describe the clinical and imaging features of this tumor in seven patients. Although secondary clinical features may rarely suggest inflammatory pseudotumor, the typical presenting symptom--painless obstructive jaundice--is indicative of malignancy. The imaging appearance of hepatic hilar biliary pseudotumor is also indistinguishable from that of cholangiocarcinoma.


[Laser-tissue interactions in urology].
The laser-tissue interaction is a complex phenomenon which is usually classified into 4 distinct mechanisms: electro-mechanical action, photoablative action, thermal action and photochemical action. Fragmentation of calculi by means of a pulsed dye laser is a good example of the electro-mechanical action. The thermal action can induce coagulation and/or volatilisation of tissues. Treatments of bladder tumors, urethral strictures and more recently benign prostatic hypertrophy are based on the laser terminal action.


Comparative study of the structural and vibroelectronic properties of porphyrin and its derivatives.
Density functional theory (DFT and time-dependent-DFT (TD-DFT) were employed to investigate the vibroelectronic structural properties of porphyrin and some derivatives: unsubstituted porphyrin (TPyr), meso-tetraphenylporphyrin (TPP), meso-tetrakis(p-sulfonatophenyl)porphyrin (TSPP), protonated-TPyr (H2TPyr), deuterated-H2TPyr (D4TPyr), protonated-TPP (H2TPP) and deuterated-H2TPP (D4TPP), protonated TSPP (H2TSPP), deuterated-H2TSPP (D4TSPP), dicationic TSPP (H6TSPP) and deuterated-H6TSPP (D8TSPP). The possible internal conversion (IC) and intersystem crossing (ISC) processes of these compounds were investigated. Finally, the relaxed ground state potential energy surface (PES) (S0), and singlet (Sn, n = 1-24) and triplet (Tn) excited state PESs of the TSPP molecule were calculated as function of the dihedral angle (Cα-Cm-Cϕ-C(ph)) rotation. The results of the calculations indicated that while the meso-substitutions caused a significant shift in frequencies when the meso-carbons within the parent-porphine (or TPyr) are involved in the vibrational motion of molecules; the protonation of the N atoms at the porphine/porphyrin core causes a significant blue shift when the H on the N atoms within the pyrroline are dominantly involved in the vibrational motions. The deuteration of N atoms not only caused a red-shift in the frequencies of the corresponding peaks below 1600 cm(-1), but also produced new vibrational modes of frequencies in the 2565-2595 cm(-1) range caused by the N-D bond stretching. Similarly, the deuteration of O atoms within the sulfonato groups (-SO3(-)) exhibited a new peak at around 2642 cm(-1) due to O-D bond stretching. The measured Raman spectrum of the H2TSPP is assigned based on the predicted Raman spectra of the compounds studied here and measured Raman spectrum of the TPP (from our previous work). The IR spectrum is assigned based on our calculations and measured IR spectra obtained from the literature. The results of the TD-DFT calculations did not only indicate that the meso-substitution and protonation of the porphyrin bring about a significant read shift in the electronic transitions; but also provided a strong evidence for the IC from the Soret band to Q-bands beside possibility of the ISC process; its existence depend on the other excited state process such as much faster vibrational relaxation; the IC and etc. The ground state PES curve (S0) of the ionic TSPP exhibited two minima at the dihedral angle (Cα-Cm-Cϕ-C) of about 66° (corresponds to the lowest ground state) and 110° (corresponds to next energetically stable state or the local minima). The energy deference between these two minima is 0.0132 eV (or 106 cm(-1)) and the highest potential energy barrier when undergoing from the lowest ground state to this local state is only 0.0219 eV (177 cm(-1); which is compatible with the thermal energy (kT) at 298 K is 207.2 cm(-1).


Update on medical treatment for Cushing's disease.
Cushing's disease (CD) is the most common cause of endogenous Cushing's syndrome (CS). The goal of treatment is to rapidly control cortisol excess and achieve long-term remission, to reverse the clinical features and reduce long-term complications associated with increased mortality. While pituitary surgery remains first line therapy, pituitary radiotherapy and bilateral adrenalectomy have traditionally been seen as second-line therapies for persistent hypercortisolism. Medical therapy is now recognized to play a key role in the control of cortisol excess. In this review, all currently available medical therapies are summarized, and novel medical therapies in phase 3 clinical trials, such as osilodrostat and levoketoconazole are discussed, with an emphasis on indications, efficacy and safety. Emerging data suggests increased efficacy and better tolerability with these novel therapies and combination treatment strategies, and potentially increases the therapeutic options for treatment of CD. New insights into the pathophysiology of CD are highlighted, along with potential therapeutic applications. Future treatments on the horizon such as R-roscovitine, retinoic acid, epidermal growth factor receptor inhibitors and somatostatin-dopamine chimeric compounds are also described, with a focus on potential clinical utility.


Nuclear and cytoplasmic distribution of cellular myb protein in human haematopoietic cells evidenced by monoclonal antibody.
A monoclonal antibody was used for analysing the expression of the cellular myb (c-myb) protein in a variety of established human tumor cell lines and its decrease after induction of differentiation. Differentiated resting human T-cells and B-cells do not express detectable amounts of c-myb protein. However, upon mitogenic stimulation in vitro T-cells exhibit strong expression of the c-myb protein as demonstrated by immunocytochemical staining and indirect immunoprecipitation. In contrast to the transformed T-lymphoblastic cell line Molt-4, where c-myb protein is a nuclear antigen, it was found in proliferating normal T-cells almost exclusively distributed in the cytoplasm. Screening of a total of 70 fresh human malignant lymphomas by immunohistochemical staining indicates the presence of the c-myb protein primarily in non-Hodgkin's lymphomas with a large growth fraction, i.e. precursor cell-derived lymphoblastic lymphomas of B-cell type and T-cell type (9/10, 3/4, respectively) and anaplastic large cell Ki-1 lymphomas (5/9), which originate from activated lymphoid cells. The c-myb protein was located predominantly in the nucleus and in some cases additionally in the cytoplasm. The different subcellular locations suggest a dual functional role. While nuclear localisation is exhibited by transformed haematopoietic cells, cytoplasmic localisation appears to be characteristic for proliferating normal T-cells and points to a second property of the c-myb protein other than interaction with DNA.


The possible contribution of a general glycosphingolipid transporter, GM2 activator protein, to atherosclerosis.
We previously found that oxidized low-density lipoprotein (LDL) elevated the expression of mRNA of GalNAcbeta1-4[NeuNAcalpha2-3]Galbeta1-4Glc-Cer (GM2) ganglioside activator protein, in human monocyte-derived macrophages. Recently, GM2 activator protein has become known as a general glycosphingolipid transporter as well as a specific cofactor for the hydrolysis of GM2 ganglioside by lysosomal beta-hexosaminidase A. Accumulation of glycosphingolipids has been observed in the serum or aorta of atherosclerotic model animals and humans. The proliferation of aortic smooth muscle cells, elevation of LDL uptake by macrophages, interfering LDL clearance by the liver, and enhancement of platelet adhesion to collagen have been proposed as the underlying mechanisms of glycosphingolipid-mediated atherogenesis. The GM2 activator protein can bind, solubilize and transport a broad spectrum of lipid molecules, indicating that GM2 activator protein may function as a general intra- and inter-cellular lipid transport protein. Collectively, elevated levels of GM2 activator protein in the aorta may be another feature of human atherosclerosis.


Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group.
The management of recurrent ovarian cancer remains controversial. Single-agent topotecan is an established treatment option, and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine. Women with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were randomly assigned to topotecan monotherapy 1.25 mg/m(2)/d, topotecan 1.0 mg/m(2) plus oral etoposide 50 mg/d, or topotecan 0.5 mg/m(2)/d plus gemcitabine 800 mg/m(2) on day 1 and 600 mg/m(2) on day 8 every 3 weeks. Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months, respectively. The primary end point was overall survival. Secondary end points included progression-free survival, objective response rates, toxicity, and quality of life (as measured by the European Organisation for Research and Treatment of Cancer [EORTC] 30-item Quality-of-Life Questionnaire). The trial enrolled 502 patients with a mean age of 60.5 years (+/- 10.2 years), 208 of whom were platinum resistant. Median overall survival was 17.2 months (95% CI, 13.5 to 21.9 months) with topotecan, 17.8 months (95% CI, 13.7 to 20.0 months) with topotecan plus etoposide (log-rank P = .7647), and 15.2 months (95% CI, 11.3 to 20.9 months) with topotecan plus gemcitabine (log-rank P = .2344). Platinum-sensitive patients lived significantly longer than platinum-refractory patients (21.9 v 10.6 months). The median progression-free survival was 7.0, 7.8, and 6.3 months, respectively. Objective response rates were 27.8%, 36.1%, and 31.6%, respectively. Patients under combined treatment were at higher risk of severe thrombocytopenia. Nonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer.


Composition and contents of fatty acids and amino acids in the mycelia of Lentinula edodes.
With the global shortages of animal protein foods, mycoprotein as a low-cost alternative source of protein by its high-protein and low-fat content has become a development trend. Lentinula edodes (L. edodes) is a healthy food with high protein and low fiber. This work evaluated the nutritional value of L. edodes mycelia, and determined the composition and contents of fatty acids and amino acids. Eleven saturated fatty acids (SFAs) and 12 unsaturated fatty acids (UFAs) were detected in the mycelia of L. edodes. The UFA content accounted for 75.7% and 73.1% of the total fatty acid content in the mycelia of strains 18 and 18N44, respectively. Linoleic acid was the major polyunsaturated fatty acid (PUFA) in the mycelia, accounting for 91.0% and 86.3% of the UFAs, respectively. The mycelia of the two strains contained 17 types of amino acids, and the essential amino acids were sufficient (357.92 ± 0.42 and 398.38 ± 4.52 mg/g pro, respectively), both close to the WHO/FAO reference protein pattern value. The most abundant essential amino acid was Lys, and the limiting amino acids were Met + Cys and Ile, respectively. The SRC values in the mycelia of the two strains were 68.07 and 54.86, and the EAAI values were 67.70 and 74.42, respectively, both being close to those of ovalbumin. It is concluded that L. edodes mycelia are rich in easily absorbed high-quality proteins and PUFAs, and can be used as a source for meat analog required by vegetarians. This study provides a scientific basis for the further utilization of mycelial resources.


Peroxiredoxin 1 interacts with androgen receptor and enhances its transactivation.
Although hypoxia is accepted as an important microenvironmental factor influencing tumor progression and treatment response, it is usually regarded as a static global phenomenon. Consequently, less attention is given to the impact of dynamic changes in tumor oxygenation in regulating the behavior of cancer cells. Androgen receptor (AR) signaling plays a critical role in prostate cancer. We previously reported that hypoxia/reoxygenation, an in vitro condition used to mimic an unstable oxygenation climate in a tumor, stimulates AR activation. In the present study, we showed that peroxiredoxin 1 (Prx1), a member of the peroxiredoxin protein family, acts as a key mediator in this process. We found that the aggressive LN3, C4-2, and C4-2B prostate cancer cell lines derived from LNCaP possess constitutively elevated Prx1 compared with parental cells, and display greater AR activation in response to hypoxia/reoxygenation. Although the cell survival-enhancing property of Prx1 has traditionally been attributed to its antioxidant activity, the reactive oxygen species-scavenging activity of Prx1 was not essential for AR stimulation because Prx1 itself was oxidized and inactivated by hypoxia/reoxygenation. Increased AR transactivation was observed when wild-type Prx1 or mutant Prx1 (C52S) lacking antioxidant activity was introduced into LNCaP cells. Reciprocal immunoprecipitation, chromatin immunoprecipitation, and in vitro pull-down assays corroborated that Prx1 interacts with AR and enhances its transactivation. We also show that Prx1 is capable of sensitizing a ligand-stimulated AR. Based on the above information, we suggest that disrupting the interaction between Prx1 and AR may serve as a fruitful new target in the management of prostate cancer.


Emergence of a febrile illness of unknown causes among the population and visitors of Upper Egypt.
This is a fictional case study for training that encourages participants to interact and apply theory into practice. A febrile illness of unknown cause that occurred in Upper Egypt in 2002 was chosen for the events. The location of Aswan was selected to define the climate, topography, and location with the characteristics that support the events. Data obtained from applied research work in Egypt was included. The case study deals with the incidence of severe cases of fever of unknown origin accompanied by neurological and intestinal symptoms, as well as a high percentage of deaths. Most of the symptoms appear in people with direct contact with farm animals especially equines and birds, or those who were near waterways, either tourism workers or tourists. Most of the infected cases or deaths have accumulated in Aswan and some in the neighbouring governorates. This case study focusses on the steps taken during an outbreak investigation, and deals with investigative challenges as well as concepts of biosafety and biosecurity.


The Role of 16S rRNA Gene Sequencing in Confirmation of Suspected Neonatal Sepsis.
Different molecular assays for the detection of bacterial DNA in the peripheral blood represented a diagnostic tool for neonatal sepsis. We targeted to evaluate the role of 16S rRNA gene sequencing to screen for bacteremia to confirm suspected neonatal sepsis (NS) and compare with risk factors and septic screen testing. Sixty-two neonates with suspected NS were enrolled. White blood cells count, I/T ratio, C-reactive protein, blood culture and 16S rRNA sequencing were performed. Blood culture was positive in 26% of cases, and PCR was positive in 26% of cases. Evaluation of PCR for the diagnosis of NS showed sensitivity 62.5%, specificity 86.9%, PPV 62.5%, NPV 86.9% and accuracy of 79.7%. 16S rRNA PCR increased the sensitivity of detecting bacterial DNA in newborns with signs of sepsis from 26 to 35.4%, and its use can be limited to cases with the most significant risk factors and positive septic screen.