Expanding the hospital nursing role: an administrative account.
In reality, role change among staff RNs is a continuous phenomenon. As medical technology increases, patient care regimes follow suit, and the staff RN is constantly called upon to apply a knowledge base in different ways and to acquire new knowledge and behaviors. The nursing administrator who keeps pace with this growth can capitalize on the phenomenon, guiding the change to see that it is progressive, that it assists the nurse in developing a more advanced nursing (as opposed to mini-physician) identity and that it does improve extant nursing practice. Undertaking a new project of this sort on the unit is likely to create a number of beneficial by-products. For example, nurse-physician rapport and communication increase as each group opens professional boundaries in defining and planning the content of role expansion. The unit's traditional operation must also be examined in the course of building in new functions. System critiques stimulate the unit's nursing manager to weed out less than optimal features of the existing nursing care delivery system. The expanded role has favorably affected nursing care at Mercy Hospital. Physicians, nurses, and most important, the patient have reaped the benefits. The nurse is able to function in a more advanced capacity, and physicians see the benefits to their patients; fewer delays in specific aspects of care delivery with a more sophisticated, higher quality of nursing care. What is exciting about this concept is that the principles could apply to virtually any RN work group that gives direct care to a homogeneous patient population.


Optical polarization properties of TPP2MnBr4 perovskite crystal adjusted by the self-trapping state.
Low-dimensional networked organic-inorganic hybrid metal halide crystal has become an emerging hotspot material due to its opportunities and advantages in the development of white-light-emitting diodes. Therefore, its photoluminescence (PL) mechanism is important. Herein, we study the PL behavior of columniform TPP2MnBr4 crystals using multi-spectroscopy. The temperature-dependent PL data show that the PL of the TPP2MnBr4 crystal originates from the recombination of a self-trapping exciton. A polarization-dependent PL test suggests that the self-trapping exciton is anisotropic, which indicates that the distribution of self-trapping states is sensitive to the orientation of the crystal axis. Space-resolved PL spectroscopy shows that the anisotropy of PL gradually weakens along the orientation of the columniform crystal, which has a longer relaxation distance than traditional light-wave-guiding behavior. Thus, anisotropy of PL can exist before it disappears in the crystal. Our results elucidate the PL mechanism of low-dimensional networked organic-inorganic hybrid metal halide crystals and provide a foundation for advanced optical polarization devices based on them.


The Apple Autophagy-Related Gene MdATG9 Confers Tolerance to Low Nitrogen in Transgenic Apple Callus.
Autophagy is an efficient degradation system for maintaining cellular homeostasis when plants are under environmental stress. ATG9 is the only integral membrane protein within the core ATG machinery that provides a membrane source for autophagosome formation. In this study, we isolated an ATG9 homologs gene in apple, MdATG9, from Malus domestica. The analysis of its sequence, subcellular localization, promoter cis-elements, and expression patterns revealed the potential function of MdATG9 in response to abiotic stressors. Overexpression of MdATG9 in apple callus conferred enhanced tolerance to nitrogen depletion stress. During the treatment, other important MdATGs were expressed at higher levels in transgenic callus than in the wild type. Furthermore, more free amino acids and increased sucrose levels were found in MdATG9-overexpression apple callus compared with the wild type in response to nitrogen starvation, and the expression levels of MdNRT1.1, MdNRT2.5, MdNIA1, and MdNIA2 were all increased higher in transgenic lines. These data suggest that, as an important autophagy gene, MdATG9 plays an important role in the maintenance of amino acids and sugars in response to nutrient starvation in apple.


Sulfobutylether-β-cyclodextrin/chitosan nanoparticles enhance the oral permeability and bioavailability of docetaxel.
The aim of this research is to develop novel chitosan nanoparticles including cyclodextrins complexes for docetaxel (DTX), evaluate the performance of nanoparticles which could enhance the oral permeability and bioavailability of DTX in vitro and in vivo. DTX/sulfobutylether-β-cyclodextrin inclusion complexes were made and it was the main ingredient to prepare the DTX/sulfobutylether-β-cyclodextrin/chitosan nanoparticles due to their promising physicochemical properties. DTX/sulfobutylether-β-cyclodextrin/chitosan nanoparticles were prepared by the ionic gelation of chitosan with tripolyphosphate in the presence of cyclodextrins. Results indicated that DTX/sulfobutylether-β-cyclodextrin inclusion complexes and docetaxel/sulfobutylether-β-cyclodextrin/chitosan nanoparticles both had good performances in the studies of release and the rat small intestinal absorption in vitro. DTX/sulfobutylether-β-cyclodextrin/chitosan nanoparticles showed preferable capability in improving the small intestinal absorption and inhibiting the efflux of DTX. In pharmacokinetics study, the DTX/sulfobutylether-β-cyclodextrin/chitosan nanoparticles increased the AUC0→t and decreased the clearance significantly, and the oral relative bioavailability of the DTX/sulfobutylether-β-cyclodextrin/chitosan nanoparticles was as high as 1447.53% compared to the pure DTX formulation. The DTX/sulfobutylether-β-cyclodextrin/chitosan nanoparticles prepared in this study have a good prospect for oral administration as an alternative of current DTX formulations.


Electrophysiologic evaluations of thymectomy in myasthenia gravis. Preliminary findings.
Electric testing was performed in 106 myasthenia gravis patients before and after transcervical thymectomy. Twenty-nine were followed for 3 to 24 months. Results were correlated with thymic pathology, duration of disease, age at operation, and follow-up clinical status. Electric improvement was significantly greater in patients without thymic germinal centers or with only rare to occasional germinal centers, in patients operated on within 1 year after onset of symptoms, and in patients under age 30. Electric improvement immediately after thymectomy heralded later clinical improvement in those patients without germinal centers or with rare to occasional germinal centers. Electric-clinical correlations were excellent in patients with longer follow-up. Serial electric testing provides an objective evaluation of the patients' clinical status post-thymectomy.


Radioisotopic method for the measurement of lipolysis in small samples of human adipose tissue.
To facilitate the study of adrenoreceptor response in small needle biopsy samples of human subcutaneous adipose tissue, we developed a dual radioisotopic technique for measuring lipolysis rate. Aliquots (20-75 mg) of adipose tissue fragments were incubated in a buffered albumin medium containing [3H]palmitate and [14C]glucose, each of high specific activity. In neutral glycerides synthesized in this system, [14C]glucose is incorporated exclusively into the glyceride-glycerol moiety and 3H appears solely in the esterified fatty acid. Alpha-2 and beta-1 adrenoreceptor activation of tissue incubated in this system does not alter rates of 14C-labeled glyceride accumulation, but does produce a respective increase or decrease in the specific activity of fatty acids esterified into newly synthesized glycerides. This alteration in esterified fatty acid specific activity is reflected in the ratio of 14C:3H in newly synthesized triglycerides extracted from the incubated adipose tissue. There is a high correlation (r = 0.90) between the 14C:3H ratio in triglycerides and the rate of lipolysis as reflected in glycerol release into the incubation medium. The degree of adrenoreceptor activation by various concentrations of lipolytic and anti-lipolytic substances can be assessed by comparing this ratio in stimulated tissue to that characterizing unstimulated tissue or the incubation medium. This technique permits the study of very small, unweighed tissue biopsy fragments, the only limitation on sensitivity being the specific activity of the medium glucose and palmitate. It is, therefore, useful for serial examinations of adipose tissue adrenoreceptor dose-response characteristics under a variety of clinical circumstances.


Structural analysis of missense mutations causing isolated sulfite oxidase deficiency.
The physiologically essential oxidation of sulfite to sulfate is catalyzed by the molybdoheme enzyme, sulfite oxidase. Deficiencies of this enzyme in human patients lead to severe neurological symptoms, which usually result in death in early childhood. Up to date eleven missense mutations in the gene encoding sulfite oxidase have been identified from sulfite oxidase deficient patients. The structural characterization of these mutants is now possible after the chicken sulfite oxidase gene has been synthesized chemically and due to the high homology to the human enzyme it provides a good model of human sulfite oxidase. This review focuses on the possible effects of the sulfite oxidase deficiency causing mutations based on our new structures of recombinant chicken sulfite oxidase.


In-Vitro Investigations of Nanoparticle Magnetic Thermotherapy: Adjuvant Effects and Comparison to Conventional Heating.
Thermotherapy, particularly magnetic nanoparticle hyperthermia, is a promising modality both as a direct cancer cell killing and as a radiosensitization technique for adjuvant therapy. Dextran-coated iron oxide nanoparticles were mixed with multiple tumor cell lines in solution and exposed to varying magnetic field regimes and combined with traditional external radiotherapy. Heating of cell lines by water bath in temperature patterns comparable to those achieved by nanoparticle hyperthermia was conducted to assess the relative value of nano-magnetic thermotherapy compared with conventional bulk heating techniques and data.


Chromosomal anomalies in cryptorchidism and hypospadias.
We have studied peripheral blood samples for chromosomal anomalies in 110 consecutive patients who had cryptorchidism and/or hypospadias. Of the patients 7 (6.4%) were found to have chromosomal anomalies. The incidence of chromosomal anomalies in patients with cryptorchidism only was 4/83 (4.8%), in patients with hypospadias only the incidence was 1/18 (5.6%) and in concomitant cases the incidence was 2/9 (22.2%). Of 69 patients with cryptorchidism and/or hypospadias who did not have any other congenital abnormalities, 3 patients (4.3%) were found to have sex chromosomal anomalies. However, of 41 patients associated with generalized congenital abnormalities including mental and growth retardation, we found 4 patients (9.8%) with autosomal anomalies. We conclude that most children with multiple associated abnormalities other than cryptorchidism and/or hypospadias should have chromosome analysis. Moreover, attention should be paid to sex chromosomal anomalies, even when patients with cryptorchidism and/or hypospadias do not have any associated generalized physical abnormalities.


How does glucose initiate proteolysis of yeast fructose-1,6-bisphosphatase?
Glucose-induced proteolysis of fructose-1,6-bisphosphatase (FBPase) in yeast (Funayama, S. et al. (1980) Eur. J. Biochem. 109, 61-66) is preceded by rapid phosphorylation of the enzyme (Müller, D., and Holzer, H. (1981) Biochem. Biophys. Res. Commun. 103. 926-933; Mazón, M. J. et al. (1982) J. Biol. Chem. 257, 1128-1130). The postulated sequence of events is as follows. Glucose causes a decrease of the cytosolic pH from 7.0 to about 6.5 (Purwin, C. et al. (1986) J. Biol. Chem. 261, in press). The change in pH activates adenylate cyclase which is at pH 6.5 2-3 times more active than at pH 7.0 The concentration of cAMP increases 2-5 times (Purwin, C. et al. (1982) Biochem. Biophys. Res. Commun. 107, 1482-1489) and thereby activates a protein kinase which phosphorylates FBPase (Pohlig, G., and Holzer, H. (1985) J. Biol. Chem. 260, 13818 to 13823). The phosphorylated enzyme is either proteolyzed in the cytosol or taken up into the vacuoles, the compartment where unspecific proteolysis takes place.


Prescription opioid abuse: dental perspectives.
Drug abuse and diversion of controlled substances prescribed by dentists will continue to be an important issue in the overall management of dental pain, and must be recognized by the dentist. If suggested guidelines, regulations, and laws are observed, the associated problems for the dentist and the entire dental team and their patients can be minimized. Pain control is an essential service and duty for dentists, and the appropriate selection and use of analgesics affords this service with the best safety and efficacy.


Inhibitors of protein synthesis V. Irreversible interaction of antibiotics with an initiation complex.
The initiation complex (t-complex) formed in a cell-free system (E. coli) from Ac-Phe-tRNA, poly(U) and washed ribosomes in the presence of initiation factors (ribosomal wash) and GTP, contains the Ac-Phe-tRNA bound quantitatively in a puromycin-reactive state. The t-complex is irreversibly inactivated by spiramycin with respect to its reactivity toward puromycin. The inactivated t-complex retains all of the Ac-Phe-tRNA bound, but it does not react with puromycin (2 x10-minus-3M) within 32 min at 25 degrees. In the case of another inhibitor protein synthesis, sparsomycin, the permanently "modified" t-complex not only retains all the bound Ac-Phe-tRNA but it can still react with puromycin. In the continuous presence of sparsomycin (1 x 10-minus-7M) the bound Ac-Phe-tRNA reacts quantitatively at a rate which is one-tenth the rate at which the t-complex reacts with puromycin, at low (6.25 x 10-minus-5M) or high (2 x 10-minus-3M) concentrations. These results are not in agreement with current views according to which aparsomycin binds to the ribosome reversibly at a single site with a KI in the range of 10-minus6-10-minus-7 M and according to which this stie is at the A'-site (puromycin site) of peptidyl transferase.


Photocatalytic reduction of hexavalent chromium and degradation of di-n-butyl phthalate in aqueous TiO2 suspensions under ultraviolet light irradiation.
Simultaneous photocatalytic reduction of chromium(VI) to the less toxic Cr(III) and degradation of di-n-butyl phthalate (DBP) in aqueous TiO2, suspension under ultraviolet light irradiation was investigated. The batch experiments were carried out in a photoreactor equipped with 350 nm lamps. The system containing Cr(VI) and DBP showed the synergistic photocatalytic decontamination as DBP facilitated Cr(VI) reduction, whereas Cr(VI) accelerated DBP degradation. This study demonstrated for the first time that two important environmental pollutants Cr(VI) and DBP could be eliminated simultaneously using UV/TiO2 process. The intermediate products of DBP degradation were identified by gas chromatography-mass spectrometry, and the reaction mechanism was proposed.


Improved cognition impairment by activating cannabinoid receptor type 2: Modulating CREB/BDNF expression and impeding TLR-4/NFκBp65/M1 microglia signaling pathway in D-galactose-injected ovariectomized rats.
Alzheimer's disease (AD) is characterized by an active inflammatory response induced by the brain's deposition and accumulation of amyloid-beta (Aβ). Cannabinoid receptor type 2 (CB2R) is expressed in specific brain areas, modulating functions, and pathophysiologies in CNS. Herein, we aimed to evaluate whether activation of CB2R can improve the cognitive impairment in the experimental AD-like model and determine the involved intracellular signaling pathway. Injection of D-galactose (150 mg/kg, i.p.) was performed to urge AD-like features in bilaterally ovariectomized female rats (OVC/D-gal rats) for 8-weeks. Then, AM1241, a CB2R-agonist (3 and 6 mg/kg), was injected intraperitoneally starting from the 6th week. Treatment with AM1241, significantly down-regulated; Toll-like receptor4 (TLR4), Myd88 (TLR4-adaptor protein) genes expression, and the pro-inflammatory cytokines (NFκB p65, TNF-α, IL-6, and IL-12). In contrast, it enhanced BDNF (the brain-derived neurotrophic factor) and CREB (the cyclic AMP response element-binding protein) as well as the immune-modulatory cytokines (IL-4 and IL-10) levels. Moreover, AM1241 lessened the immune-expression of GFAP, CD68, caspase-3, and NFκB p65 markers and mended the histopathological damage observed in OVC/D-gal rats by decreasing the deposition of amyloid plaques and degenerative neuronal lesions, as well as improving their recognition and learning memory in both novel object recognition and Morris water maze tests. In conclusion, activating CB2R by the selective agonist AM1241 can overrun cognitive deficits in OVC/D-gal rats through modulation of TLR4/ NFκB p65 signaling, mediated by modulating CREB/BDNF pathway, thereby can be applied as a potential therapeutic strategy in AD treatment.


Next-generation studies of mating system evolution.
The specificity of mate selection can vary from wantonly indiscriminate to extraordinarily choosy, and depends in large part on molecules expressed on the surfaces of sperm and eggs. Understanding the evolution of this specificity of gamete recognition leads to important insights into the evolution of reproductive isolation and speciation. One productive area of research has focused on genes that encode gamete recognition proteins in broadcast-spawning marine invertebrates. These gene products are relatively accessible to biochemical and cellular analyses of expression and function, and they mediate almost all of the elements of mate selection and specificity between males and females of such species. However, genetic analyses of their evolution are currently limited to a few combinations of molecules and taxa, and may miss the broader view of adaptive responses to selection on mating specificity across many genes and many types of mating systems. A transcriptomic study shows how next-generation sequencing methods and analyses could relatively easily broaden such studies to more clades, deepen those studies to include more of the interacting molecular parts that mediate gamete recognition, and eventually lead to a more complete understanding of the molecular basis for mating system variation and its evolutionary response to selection.


Methane Suppresses Microglial Activation Related to Oxidative, Inflammatory, and Apoptotic Injury during Spinal Cord Injury in Rats.
We investigated the hypothesis that methane-rich saline (MS) can be used to repair spinal cord injury (SCI) in a rat model through suppressing microglial activation related to oxidative, inflammatory, and apoptotic injury. MS was injected intraperitoneally in rats after SCI. Hematoxylin-eosin (HE) staining, oxidative stress, inflammatory parameters, and cell apoptosis were detected 72 h after SCI to determine the optimal dose. Then, we investigated the protective mechanisms and the long-term effects of MS on SCI. HE and microglial activation were observed. Neurological function was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale. MS can significantly decrease infarct area and inhibit oxidative stress, inflammation, and cell apoptosis 72 h following SCI. The MS protective effect at a dose of 20 ml/kg was better. Moreover, MS can significantly suppress microglial activation related to oxidative and inflammatory injury after SCI and improve hind limb neurological function. MS could repair SCI and reduce the release of oxidative stress, inflammatory cytokines, and cell apoptosis produced by activated microglia. MS provides a novel and promising strategy for the treatment of SCI.


Nucleophilic reactivities of carbanions in water: the unique behavior of the malodinitrile anion.
The kinetics of the reactions of nine carbanions 1a-i, each stabilized by two acyl, ester, or cyano groups, with benzhydrylium ions in water were investigated photometrically at 20 degrees C. Because the competing reactions of the benzhydrylium ions with water and hydroxide ions are generally slower, the second-order rate constants of the reactions of the benzhydrylium ions with the carbanions can be determined with high precision. The rate constants thus obtained can be described by the Ritchie equation, log(k/k(0)) = N(+) (eq 1), which allows us to calculate Ritchie N(+) parameters for a series of stabilized carbanions, for example, malonate, acetoacetate, malodinitrile, etc., and compare them with those of other n-nucleophiles in water (hydroxide, amines, azide, thiolates, etc.). Because the Ritchie relationship (eq 1) is a special case of the more general relationship log k = s(N + E) (eq 4), the reactivity parameters N and s for the carbanions 1a-i can also be calculated and compared with the nucleophilic reactivities of a large variety of n-, pi-, and sigma-nucleophiles, including reactivities of carbanions in dimethyl sulfoxide. While the acyl and ester substituted carbanions are approximately 3 orders of magnitude less reactive in water than in dimethyl sulfoxide, the malodinitrile anion (1i) shows almost the same reactivity in both solvents. Correlations between the nucleophilic reactivities of carbanions with the pK(a) values of the corresponding CH acids reveal that the malodinitrile anion (1i) is considerably more nucleophilic than was expected on the basis of its pK(a) value. This deviation is assigned to the exceptionally low Marcus intrinsic barriers of the reactions of the malodinitrile anion (1i).


Clinically unsuspected Hodgkin's lymphoma diagnosed primarily from bone marrow trephine biopsy: report of six cases.
Bone marrow may be the initial or rarely the only site of involvement in Hodgkin's lymphoma. A high index of suspicion is required to pick up the histopathological changes of Hodgkin's lesions in the bone marrow like necrosis, presence of Reed-Sternberg cell or its variant in a polymorphic background infiltrate, focal fibrosis and myxoid change especially in the absence of classical clinical picture. Bone marrow with immunohistochemistry has a valuable role in the staging and in the diagnosis of primary medullary Hodgkin's lymphoma. B-symptoms may easily masquerade as an infectious process as in all our cases the patients had fever as a presenting feature, in four of them tuberculosis was suspected clinically and two had received antitubercular therapy elsewhere. We report six human immunodeficiency virus-negative patients diagnosed over a period of 5 years in which the initial diagnosis of Hodgkin's lymphoma was suggested from bone marrow histology.


Survival and cause of death in rheumatoid arthritis: a 25-year prospective followup.
In a 25-year prospective followup of 209 patients with rheumatoid arthritis, median life expectancy was shortened by 7 years in males and by 3 years in females when compared with the general population. The surplus mortality was associated in decreasing order with the disease itself, associated respiratory, urogenital and general infections, and with upper gastrointestinal tract disease, mainly bleeding.


Is the long-term survival of patients with intracranial glioblastoma multiforme overstated?
The 5-year survival rate for intracranial glioblastoma multiforme (GBM) has remained at 4-5% for the last 30 years, in spite of multiple randomized prospective trials. The authors hypothesized, based on the literature, that even this remarkably poor survival rate is an overstatement. They investigated this hypothesis using the the Duke University Medical Center Tumor Registry. The authors reviewed all patients with the diagnosis of intracranial GBM recorded in the Duke University Medical Center Tumor Registry from the registry's inception in 1976 through 1996. This search identified a population of patients with a minimum of 5 years of follow-up. Each of the long-term survivors was assigned a code number for clinical information. The pathology slides were provided to a neuropathologist in a coded fashion so that the patients could not be identified. The neuropathologist reviewed the slides to analyze the presence or absence of nine histologic factors. A match technique was used to identify a control population of patients with GBM who were not 5-year survivors and were all deceased. The control population was compared with the study population to ascertain if there are histologic correlates associated with long-term survivorship. The authors identified 766 patients recorded by the tumor registry as having an intracranial GBM with a minimum of 5 years of follow up. Of the total population, 32 patients initially appeared to be 5-year survivors (4%). Upon review of the medical records for these 32 patients, however, the authors found only 17 patients who were truly 5-year survivors. The most common reason for miscoding was the presence of a low-grade astrocytoma that subsequently dedifferentiated into GBM. The 17 long-term survivors included 11 males and 6 females. Their mean age at diagnosis was 40.2 years. Therapy consisted of a macroscopic total resection in 4 patients (22%), a biopsy in 1 patient (6%), a subtotal resection in 10 patients (56%), and unknown extent of resection in 2 patients (11%). All patients received partial brain irradiation (mean dose, 62.6 Gy) and chemotherapy. Thirteen different single-agent or combination chemotherapy programs were used. Two patients also received I-131 monoclonal antibody therapy. Analysis of the nine histopathologic factors studied showed that intermediate fibrillary elements were more common and small anaplastic elements were less common in the long-term survivors than in the control population. Survival data on intracranial GBM, based on tumor registry data, should be interpreted cautiously. Reliable conclusions can only be drawn when such data are supplemented with clinical information and the histopathology is reviewed carefully. The group of long-term survivors in the current study were younger than the typical GBM population. Conventionally treated patients with GBM, chosen from an unselected population from a tumor registry, have a smaller chance of long-term survival than is generally believed.


Effects of Combined Endurance and Resistance Training in Women With Multiple Sclerosis: A Randomized Controlled Study.
Purpose: To test the hypothesis that combined resistance and endurance training would improve muscle strength, fatigue, depression, and quality of life in persons with MS. Methods: Twenty-seven women with MS were randomly assigned to either control (CON, n = 13) or the experimental (EXP, n = 14) group. The participants in the EXP group trained twice a week for 12 weeks, followed by 12 weeks of detraining. Both CON and EXP groups were tested before and after 12 weeks of the intervention period, as well as 12 weeks after training cessation (follow-up), where measures of muscle strength, fatigue, depression, and quality of life were evaluated. Results: There were significant changes in maximal voluntary isometric contraction (MVIC), 1RM leg extension, and 1RM chest press following the intervention period in the EXP group (P < 0.05), but not in the CON group (P > 0.05). These changes persisted after 12 weeks of detraining. Similar findings were found for fatigue, depression, and physical and mental composites of quality of life. Conclusion: These results suggest that combined exercise training, at a minimum, prevents the disease-related deterioration of muscular performance and quality of life and well-being in persons with MS.


Genotypes of Epstein-Barr virus (EBV1/EBV2) in individuals with infectious mononucleosis in the metropolitan area of Belém, Brazil, between 2005 and 2016.
Two types of Epstein Barr virus (EBV1/EBV2) have been shown to infect humans. Although their genomes are similar, the regions containing the EBNA genes differ. This study aimed to characterize the EBV genotypes of infectious mononucleosis (IM) cases in the metropolitan region of Belém, Brazil, from 2005 to 2016. A total of 8295 suspected cases with symptoms/signs of IM were investigated by infectious disease physicians at Evandro Chagas Institute, Health Care Service, from January 2005 to December 2016. Out of the total, 1645 (19.8%) samples had positive results for EBV by enzyme immunoassay and 251 (15.3%) were submitted to polymerase chain reaction (PCR) technique, using the EBNA3C region, in order to determine the type of EBV. Biochemical testing involving aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase were also performed. EBV type was identified by PCR in 30.3% (76/251) of individuals; of those, 71.1% (54/76) were classified as EBV1, 17.1% (13/76) as EBV2, and 11.8% (9/76) as EBV1 + EBV2. The main symptoms/signs observed with EBV1 infection were cervical lymphadenopathy (64.8%, 35/54), fever (63%, 34/54), headache (20.4%, 11/54), arthralgia (20.4%, 11/54), and exanthema (18.5%, 10/54). EBV2 infection was detected in all but two age groups, with an average age of 24 years. The most common signs/symptoms of EBV2 were fever (76.9%, 10/13), average duration of 18 days, and lymphadenopathy (69.2%, 9/13). In contrast, EBV1 + EBV2 coinfections were more frequent in those aged five years or less (20.0%, 2/10). The symptoms of EBV1 + EBV2 coinfection included fever (66.7%, 6/9), and cervical lymphadenopathy and headache (33.3%, 3/9) each. The mean values of hepatic enzymes according to type of EBV was significantly different (p < 0.05) in those EBV1 infected over 14 years of age. Thus, this pioneering study, using molecular methods, identified the EBV genotypes in 30.3% of the samples, with circulation of EBV1, EBV2, and EBV1 + EBV2 co-infection in cases of infectious mononucleosis in the northern region of Brazil.


Neuroproteomics and microRNAs studies in multiple sclerosis: transforming research and clinical knowledge in biomarker research.
Multiple sclerosis (MS) is a complex disease characterized by extensive phenotypic variability. Biomarkers to capture the different aspects of MS heterogeneity, and to help make a diagnosis and monitor disease progression, while providing insights into etiopathogenesis and response to treatment, are urgently needed. Omics technologies and research efforts with microRNAs have provide unparalleled opportunities for exploring altered protein profiles associated with molecular mechanisms of disease, substantially expanding the list of candidate biomarkers for MS. This review presents evidence from proteomic studies that have focused on identification of biomarkers released in biofluids as a result of the different pathophysiological processes of MS. Also discussed is the emerging role of miRNAs as complementary biomarkers related to cellular processes occurring in MS patients. Also provided is an overview of candidate biomarkers that have been proposed for elucidating pathophysiological processes and disease activity and for guiding clinical diagnosis and/or therapeutic interventions in MS.


Musculoskeletal manifestations of systemic lupus erythematosus.
The musculoskeletal system is involved in nearly all patients with SLE. Transient arthralgias or arthritis are common and, in some patients, there is a progression to rheumatoid-like nonerosive hand deformities (Jaccoud's syndrome). The major disabling type of joint disease in lupus is articular osteonecrosis, often induced by high-dose corticosteroids. Rare forms of musculoskeletal manifestations of lupus include spontaneous tendon rupture, crystalline arthropathies, subcutaneous calcifications, and inflammatory myopathy.


[Epithelium transplantation with cultivated keratinocytes].
Efforts for a skin substitute from cultured cells have been made since many years. Epidermal cells are able to proliferate in culture vessels under strictly defined culture conditions. The gained expanded epithelial layer can be used as transplant. The culture methods of Green and Eisinger are discussed. In the last couple of years in vitro expanded epithelium was used as wound coverage, especially for major burns. Autologous transplanted epithelium is accepted perfectly under optimal wound bed conditions. Reports on the acceptance of allogenic transplanted cultivated keratinocytes are contradictory, possibly so far unidentified antigens are responsible for the rejection. To optimize the skin substitute keratinocytes can be cultured on different mesenchymal substrates. Possibly epidermal appendages can be included in the future.


Novel function of MDA-9/Syntenin (SDCBP) as a regulator of survival and stemness in glioma stem cells.
Glioblastoma multiforme (GBM) is an aggressive cancer with current therapies only marginally impacting on patient survival. Glioma stem cells (GSCs), a subpopulation of highly tumorigenic cells, are considered major contributors to glioma progression and play seminal roles in therapy resistance, immune evasion and increased invasion. Despite clinical relevance, effective/selective therapeutic targeting strategies for GSCs do not exist, potentially due to the lack of a definitive understanding of key regulators of GSCs. Consequently, there is a pressing need to identify therapeutic targets and novel options to effectively target this therapy-resistant cell population. The precise roles of GSCs in governing GBM development, progression and prognosis are under intense scrutiny, but key upstream regulatory genes remain speculative. MDA-9/Syntenin (SDCBP), a scaffold protein, regulates tumor pathogenesis in multiple cancers. Highly aggressive cancers like GBM express elevated levels of MDA-9 and contain increased populations of GSCs. We now uncover a unique function of MDA-9 as a facilitator and determinant of glioma stemness and survival. Mechanistically, MDA-9 regulates multiple stemness genes (Nanog, Oct4 and Sox2) through activation of STAT3. MDA-9 controls survival of GSCs by activating the NOTCH1 pathway through phospho-Src and DLL1. Once activated, cleaved NOTCH1 regulates C-Myc expression through RBPJK, thereby facilitating GSC growth and proliferation. Knockdown of MDA-9 affects the NOTCH1/C-Myc and p-STAT3/Nanog pathways causing a loss of stemness and initiation of apoptosis in GSCs. Our data uncover a previously unidentified relationship between MDA-9 and GSCs, reinforcing relevance of this gene as a potential therapeutic target in GBM.


Academia-industry collaboration in continuing medical education: description of two approaches.
Although concerns have been raised about industry support of continuing medical education (CME), there are few published reports of academia-industry collaboration in the field. We describe and evaluate Pri-Med, a CME experience for primary care clinicians developed jointly by the Harvard Medical School (HMS) and M/C Communications. Since 1995, 19 Pri-Med conferences have been held in four cities, drawing more than 100,000 primary care clinicians. The educational core of each Pri-Med conference is a 3-day Harvard course, "Current Clinical Issues in Primary Care." Course content is determined by a faculty committee independent of any commercial influence. Revenues from multiple industry sources flow through M/C Communications to the medical school as an educational grant to support primary care education. Pri-Med also offers separate pharmaceutical company-funded symposia. Comparing the two educational approaches during four conferences, 221 HMS talks and 103 symposia were presented. The HMS course covered a wide range with 133 topics; the symposia focused on 30 topics, most of which were linked to recently approved new therapeutic products manufactured by the funders. Both the course and the symposia were highly rated by attendees. When CME presentations for primary care physicians receive direct support from industry, the range of offered topics is narrower than when programs are developed independently of such support. There appear to be no differences in the perceived quality of presentations delivered with and without such support. Our experience suggests that a firewall between program planners and providers of financial support will result in a broader array of educational subjects relevant to the field of primary care.


Interleukin-2, Ipilimumab, and Anti-PD-1: clinical management and the evolving role of immunotherapy for the treatment of patients with metastatic melanoma.
Treatment of metastatic melanoma has changed dramatically in the past 5 years with the approval of six new agents (vemurafenib, dabrafenib, trametinib, ipilimumab, pembrolizumab, and nivolumab) by the US Food and Drug Administration (FDA). This review will compare the immunotherapies recently approved by the FDA (ipilimumab, nivolumab and pembrolizumab) with the long-approved immunotherapy, interleukin-2. Additional consideration will be given to the evolving landscape, including the opportunities for combination regimens. Immunotherapies have distinct mechanisms of action and unique response kinetics that differ from conventional cytotoxic and targeted therapies, and have a range of adverse events that can be safely managed by experienced health-care providers. Data suggest immunotherapies can result in long-term survival in a proportion of patients. This dynamic and evolving field of immunotherapy for melanoma will continue to offer challenges in terms of optimal patient management for the foreseeable future.


Atypical periosteal reaction and unusual bone involvement of ameloblastoma: A case report with 8-year follow-up.
Unusual radiographic findings of intraosseous ameloblastoma have been reported and discussed. In the case discussed herein, cone-beam computed tomography (CBCT) clearly showed many radiographic features that were ambiguous on conventional radiographs, including an ill-defined periphery, extensive superficial buccal extension with minimal lingual extension, obvious bucco-crestal expansion, and multiple triangular (Codman's triangle-like) areas of periosteal reaction. Based on the above-mentioned findings, the differential diagnosis was a long-term infected benign or low-grade malignant lesion. An incisional biopsy was performed, and the histopathologic diagnosis was acanthomatous ameloblastoma. Recurrence of the lesion was clearly detected on CBCT images at 4 and 8 years after surgery. These unusual radiographic findings have never been reported to be associated with ameloblastoma, and thus may contribute to novel concepts in radiographic interpretation in the future. This report also underscores the important role played by CBCT as a comprehensive diagnostic tool and for definite confirmation of recurrence.


Endoscopic carpal tunnel release for recurrent carpal tunnel syndrome after previous open release.
Recurrent carpal tunnel syndrome from various causes has been shown to occur in up to 19% of patients. Endoscopic carpal tunnel release has been used to decompress the median nerve in carpal tunnel syndrome for many years. However, endoscopic release for recurrent carpal tunnel syndrome after previous surgical release has not been reported. Nine hands in six patients had recurrent carpal tunnel syndrome five to 20 years after previous open carpal tunnel release. All the cases were successfully treated with endoscopic release.


Identification of mycobacterial HSP70 reactive human T cell clones discriminating between M. tuberculosis and M. leprae.
M. tuberculosis reactive CD4+ T cell clones were established from a BCG vaccinated donor and tested for proliferative responses against complex mycobacterial antigens like M. tuberculosis, M. leprae, and PPD, as well as the recombinant M. tuberculosis HSP70 and HSP65 antigens from both M. tuberculosis and M. leprae. This screening permitted the identification of T cell clones specifically recognizing the mycobacterial HSP70 or HSP65 antigen. All HSP65 reactive T cell clones were cross-reactive for M. tuberculosis and M. leprae, whereas three HSP70 reactive T cell clones only recognized M. tuberculosis. In addition, HLA typing and blocking experiments with anti-HLA antibodies revealed that antigen presentation to all M. tuberculosis reactive T cell clones was restricted by HLA-DR3 molecules. We have thereby demonstrated the presence of human T cell specificities directed against the mycobacterial HSP70 antigen that are able to discriminate between M. tuberculosis and M. leprae.


Effect of laser acupuncture on monosymptomatic nocturnal enuresis in adolescent females: A randomized controlled trial.
Nocturnal enuresis (NE) is prevalent in children and adolescents and affects their social life later. Therefore, the objective of this study was to ascertain laser acupuncture (LA) therapy's effect on NE in adolescent females. Sixty adolescent females diagnosed with chronic monosymptomatic nocturnal enuresis (MNE) were randomly divided into two equal groups: The intervention group (received LA and desmopressin) and the control group (received desmopressin only) (n = 30 each). Treatment was delivered and LA was used three times a week for 12 successive weeks. Abdominal ultrasonography and voiding calendar were used to assess bladder capacity and maximum voiding volume (MVV), respectively. The frequency of bed wetness was assessed throughout the trial period in a diary. Statistically significant differences were reported in the intervention group. Bladder capacity significantly increased in the intervention group (LA and desmopressin) than in the control group. The results of this study suggest the beneficial influences of LA on MNE, despite the very poor quality of the literature's available evidence.


Studies on the formation, temporal evolution and forensic applications of camera "fingerprints".
A series of experiments was conducted by exposing negative film in brand new cameras of different make and model. The exposures were repeated at regular time intervals spread over a period of 2 years. The processed film negatives were studied under a stereomicroscope (10-40x) in transmitted illumination for the presence of the characterizing features on their four frame-edges. These features were then related to those present on the masking frame of the cameras by examining the latter in reflected light stereomicroscopy (10-40x). The purpose of the study was to determine the origin and permanence of the frame-edge-marks, and also the processes by which the marks may probably alter with time. The investigations have arrived at the following conclusions: (i) the edge-marks have originated principally from the imperfections received on the film mask from the manufacturing and also occasionally from the accumulated dirt, dust and fiber on the film mask over an extended time period. (ii) The edge profiles of the cameras have remained fixed over a considerable period of time so as to be of a valuable identification medium. (iii) The marks are found to be varying in nature even with those cameras manufactured at similar time. (iv) The influence of f/number and object distance has great effect in the recording of the frame-edge marks during exposure of the film. The above findings would serve as a useful addition to the technique of camera edge-mark comparisons.


Reducing fresh full term intrapartum stillbirths through leadership and accountability in a low-resource setting, Mpilo Central Hospital, Bulawayo, Zimbabwe.
Stillbirths are distressing to the parents and healthcare workers. Globally large numbers of babies are stillborn. A number of strategies have been implemented to try and reduce stillbirths worldwide. The objective of this study was to assess the impact of leadership and accountability changes on reducing full term intrapartum stillbirths. Leadership and accountability changes were implemented in January 2016. This retrospective cohort study was carried out to assess the impact of the changes on fresh full term intrapartum stillbirths covering the period 6 months prior to the implementation date and 12 months after the implementation date. The changes included leadership and accountability. Fresh full term stillbirths (>37 weeks gestation) occurring during the intrapartum stage of labour were analysed to see if there would be any reduction in numbers after the measures were put in place. There was a reduction in the number of fresh full term intrapartum stillbirths after the introduction of the measures. There was a statistical difference before and after implementation of the changes, 50% vs 0%, P = 0.025. There was a reduction in the time it took to perform an emergency caesarean section from a mean of 30 to 15 min by the end of the study, a 50% reduction. Clear and consistent clinical leadership and accountability can help in the global attempts to reduce stillbirth figures. Simple measures can contribute to improving perinatal outcomes.


Zoophilia in an adolescent with high-functioning autism from Sri Lanka.
Zoophilia is a rare paraphilic disorder with intense sexual urges involving animals. Autism is characterised by impairments in social communication and repetitive, restricted behaviours (RRB). Reported cases of zoophilia are limited worldwide, and zoophilia in autism is rarer. This is a case report describing this unique and relatively unrecognised association in a male adolescent from Sri Lanka. A 17-year-old boy diagnosed with autism has average intelligence and academic capabilities. He had spent increasing time at his grandparents' cattle house. First, he was found masturbating near the cows and later having penetrative intercourse with a heifer. The shocked parents first sought traditional healing in the form of 'thovil', a demonic ritual of exorcist nature. Later, clinical evaluation found intense sexual urges towards cattle, which had led to marked distress and academic impairment. Sex hormone profile was normal. The adolescent was treated with a combination of cognitive-behaviour therapy and a selective serotonin reuptake inhibitor. We postulate that his persistent social difficulties contributed to the development of a paraphilic disorder. Unlike with his RRBs, he was markedly distressed about this sexual behaviour. Further research is required to explore this rarely reported, potential association.


cDNA sequence of a new chicken embryonic rho-globin.
In order to use specific DNA probes for the study of developmentally regulated gene expression, we have prepared cDNA clones corresponding to chicken embryonic globins by inserting cDNA.mRNA hybrids into the Pst I site of the plasmid pBR322 by using poly(dG) and poly(dC) linkers. The nucleotide sequence of the insert of one clone, representing a nearly full-length copy of an embryonic beta-like globin cDNA, has been determined. The amino acid sequence of the globin encoded by this insert is identical to the sequence of embryonic rho-globin, except for four amino acid residues near the carboxy terminus. Comparison of mRNA sequences of the embryonic and adult chicken beta-globins indicates the presence of extensive deletions in the 3' untranslated region of the embryonic gene.


Cultural characteristics and fatty acid composition of Corynebacterium acnes.
A detailed study of the cultural characteristics and cellular fatty acid composition of 27 isolates of Corynebacterium acnes was performed to establish the properties by which this organism may be identified and characterized. The fatty acids were extracted directly from whole cells and examined as methyl esters by gas-liquid chromatography. Each strain possessed a similar fatty acid profile which was characterized by a large percentage of C15 branched-chain acid. Uniformity in certain biochemical reactions and cultural characteristics was also observed. All strains were catalase-positive, nonmotile, and urease-negative, reduced nitrate, liquefied gelatin, failed to hydrolyze esculin and starch, and gave a positive methyl red test. Glucose, fructose, and glycerol were fermented, but not lactose, salicin, sucrose, maltose, xylose, or arabinose. Production of hydrogen sulfide and indole, fermentation of mannitol, and hemolytic activity were variable characteristics. Two species of the genus Propionibacterium were also tested and found to be similar to C. acnes both in cultural characteristics and fatty acid composition. The results strengthen previous suggestions that C. acnes should be classified in the genus Propionibacterium.


Photocatalytic degradation of 2,4-dichlorophenoxyacetic acid and 4-chloro-2-methylphenoxyacetic acid in water by using TiO2.
The photocatalytic degradation of many chlorinated organic compounds by semiconductor particles, has been widely recognised as a promising method of water and wastewater treatment process. In the present work the photocatalytic transformation of 2,4-D and MCPA in aqueous solution with 2 g l(-1) suspended TiO2 is demonstrated. The formation of several intermediates has been observed. The photodegradation rate increases with increasing pH. The photocatalytic transformation of 2,4-D and MCPA over TiO2 in solution containing hydrogen peroxide has been also studied. H2O, accelerated significantly the reaction rate of 2, 4-D and MCPA. The partial inhibition by ethanol is attributed to the scavenging of OH radicals involved in the first step of the reaction. Finally, from these results, a mechanism is proposed. This photocatalytic method has good potential for application on a large scale.


The arrest of biological time as a bridge to engineered negligible senescence.
Biological systems can remain unchanged for several hundred years at cryogenic temperatures. In several hundred years, current rapid scientific and technical progress should lead to the ability to reverse any biological damage whose reversal is not forbidden by physical law. We therefore explore whether contemporary people facing terminal conditions might be preserved well enough today for their eventual recovery to be compatible with physical law. The ultrastructure of the brain can now be excellently preserved by vitrification, and solutions needed for vitrification can now be distributed through organs with retention of organ viability after transplantation. Current law requires a few minutes of cardiac arrest before cryopreservation of terminal patients, but dogs and cats have recovered excellent brain function after 16-60 min of complete cerebral ischemia. The arrest of biological time as a bridge to engineered negligible senescence, therefore, appears consistent with current scientific and medical knowledge.


TLR4 mediates pneumolysin-induced ATF3 expression through the JNK/p38 pathway in Streptococcus pneumoniae-infected RAW 264.7 cells.
Activating transcription factor-3 (ATF3) acts as a negative regulator of cytokine production during Gram-negative bacterial infection. A recent study reported that ATF3 provides protection from Streptococcus pneumoniae infection by activating cytokines. However, the mechanism by which S. pneumoniae induces ATF3 after infection is still unknown. In this study, we show that ATF3 was upregulated via Toll-like receptor (TLR) pathways in response to S. pneumoniae infection in vitro. Induction was mediated by TLR4 and TLR2, which are in the TLR family. The expression of ATF3 was induced by pneumolysin (PLY), a potent pneumococcal virulence factor, via the TLR4 pathway. Furthermore, ATF3 induction is mediated by p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Thus, this study reveals a potential role of PLY in modulating ATF3 expression, which is required for the regulation of immune responses against pneumococcal infection in macrophages.


Correlation of In Vivo and In Vitro Assay Results for Assessment of Free Radical Scavenging Activity of Green Tea Nutraceuticals.
Green tea (GT)-derived catechins; epigallocatechin gallate (EGCG) in particular are commonly used nutraceuticals for their free-radical scavenging activity (FRSA). The influence of photodegradation on the protective power of GT nutracenticals against oxidative stress was thoroughly explored. Photodegradation of GT extracts was carried out and monitored using orthogonal stability-indicating testing protocol; in vitro and in vivo assays. Total polyphenol content (TPC) and FRSA were determined spectrophotometrically while EGCG was selectively monitored using SPE-HPLC. In vivo assessment of photodegraded samples was investigated via measuring a number of biomarkers for hepatic oxidative stress and apoptosis (caspase-3, inducible nitric oxide synthase, nitric oxide, mitogen-activated protein kinase, glutathione, thiobarbituric acid reactive substances, nuclear factor kappa beta, and nuclear factor erythroid 2-related factor) as well as liver damage (alanine transaminase and aspartate transaminase) in serum of rats previously subjected to oxidative stress. Results showed complete degradation of EGCG in photodegraded green tea samples with no correlation with either TPC or FRSA. On the other hand, in vivo assay results revealed not only loss of activity but formation of harmful pro-oxidants. Photostability was found crucial for the protective effect of GT extract against lead acetate insult. Results confirmed that careful design of quality control protocols requires correlation of chemical assays to bioassays to verify efficacy, stability, and most importantly safety of nutraceuticals.


Evaluation of the sysmex UF-5000 fluorescence flow cytometer as a screening platform for ruling out urinary tract infections in elderly patients presenting at the Emergency Department.
In this study, we evaluated the performance of the flow cytometer-based Sysmex UF-5000 automated urine analyzer as a screening tool for ruling out urinary tract infections in elderly patients presenting at the emergency department. A total of 1119 unselected patient samples (including 544 samples from elderly patients) submitted for urine culture were included in this study. Samples were measured on UF-5000 and dipsticks and the results were compared with interpretation of culture results, which is the gold standard. We obtained a diagnostic sensitivity of 99% and specificity of 51% with a low rate of false negatives (0.2%) and a negative predictive value of 99% at 108 colony forming bacteria/L (CFB/L). A bacterial count ≥ 50x106/L or yeast like cells ≥ 25x106/L was used as the cutoff value. At this cutoff value, 30% of the urine cultures would have been redundant. This resulted in 35% false positive samples, mainly due to particle contamination or nongrowing bacteria. In comparison, at best, the dipsticks have a diagnostic sensitivity of 89%, a specificity of 52% and a negative predictive value of 92% at 108 CFB/L.


[Clinical evaluation of management of superior mediastinal metastasis from thyroid carcinoma with systemic superior mediastinal dissection via sternotomy approach: 12 cases report].
Few research of surgery for superior mediastinal metastasis from thyroid carcinoma has been reported. Previous surgical approach from neck had the problems of easy damage of nerve and vessels and the difficulty of clearance of lymph nodes. This study was designed to assess the value of systemic superior mediastinal lymph node dissection via sternotomy for superior mediastinal metastasis from differentiated thyroid carcinoma. A retrospective study was performed to analyze the clinical pathologic data as well as the outcome of 12 cases of differentiated thyroid carcinoma treated with systemic superior mediastinal lymph node dissection via sternotomy approach from April 1995 to April 2002, including 7 cases of papillary adenocarcinoma and 5 cases of medullary carcinoma. Pathologically, the incidence rates of metastasis to anteriotracheal lymph node, paratracheal lymph node, anterior superior vena cava, and anterior innominate artery lymph nodes were 55.6% (25/45), 57.1% (36/63), 42.1% (8/19) and 30% (3/10), respectively. All cases are still alive in one to seven years follow-up period. The median follow-up was 32 months. Upper mediastinal lymph nodes were recurrent in one case; distant metastasis occurred in two cases. Systemic superior mediastinal lymph node dissection via sternotomy approach can be employed in treating superior mediastinal lymph node metastasis from differentiated thyroid carcinoma due to its safety and relatively satisfactory outcome.


Characterization of a microsatellite in the promoter region of the IGF1 gene in domestic horses and other equids.
Insulin-like growth factor 1 (IGF1) regulates growth and metabolic functions in vertebrates. A dinucleotide repeat sequence located at the promoter region of the IGF1 gene has been reported in several vertebrate species and may affect the control of the transcriptional activity of this gene. The genotypes of animals from seven horse breeds were determined in order to study the potential association of allelic forms of this microsatellite with adult body size differences found in domestic horses. Among these breeds, five alleles were found. Breed-specific differences in adult body size could not be attributed to the presence or absence of any of the alleles observed. In addition, animals representing five other equid species were typed. Examples of apparent species-specific alleles were found. However, overlapping polymorphic size ranges preclude this microsatellite from being an absolute identifier for species or hybrid status in equids. The polymorphisms found at this IGF1 locus are useful for synteny and linkage mapping.


Primary T-cell CNS lymphoma presenting with leptomeningeal spread and neurolymphomatosis.
Primary CNS lymphoma (PCNSL), a rare form of non-Hodgkin lymphoma that is confined to the brain, is usually of B-cell origin. Primary leptomeningeal lymphoma, regardless of T or B-cell origin, is an unusual site of presentation. Out of 100 consecutive PCNSL patients that we have followed up in our center during the last 10 years, five had T-cell lymphoma (5%). All presented with leptomeningeal involvement as the sole manifestation and four of them presented with neuronal lymphomatosis. Presenting symptoms included signs of elevated intracranial pressure with 6th nerve palsy; headache and bilateral 3rd nerve palsy; mononeuritis multiplex and unilateral hearing loss; bilateral 7th nerve paralysis and bilateral uveitis. Because neither the CSF nor the MRI were indicative, meningeal or nerve biopsies were required for conclusive diagnosis. Four patients died 10-19 months from disease onset and one patient is alive 36 months following the diagnosis. We conclude that T-cell PCNSL can present as an isolated leptomeningeal involvement which may be associated with neurolymphomatosis affecting cranial and peripheral nerves. These manifestations mimic other neurological conditions such as pseudotumor cerebri or vasculitis. Diagnosis is difficult and, as a result, frequently delayed. This calls for early consideration of meningeal or nerve biopsy whenever CSF findings are inconclusive.


Demystifying immunotherapy in prostate cancer: understanding current and future treatment strategies.
Immunotherapy has emerged as a viable therapeutic option for patients with prostate cancer. There are multiple potential strategies that use the immune system, including therapeutic cancer vaccines that are designed to stimulate immune cells to target antigens expressed by cancer cells. Sipuleucel-T is a vaccine currently approved for the treatment of minimally symptomatic metastatic prostate cancer, whereas the vaccine PSA-TRICOM and the immune-checkpoint inhibitor ipilimumab are in phase III testing. Although there are no short-term changes in disease progression or available biomarkers to assess response, these agents appear to improve survival. One hypothesis suggests that this apparent paradox can be explained by the growth-moderating effects of these treatments, which do not cause tumor size to diminish, but rather stall or slow their growth rate over time. For this reason, the use of immunotherapy earlier in the disease process is being investigated. Another approach is to block immune-regulatory mechanisms mediated by the molecules cytotoxic T lymphocyte antigen 4 and programmed cell death protein 1. Additional future strategies will combine immunotherapy with other standard therapies, potentially enhancing the latter's clinical impact and thereby improving both time to progression and overall survival due to the combined effects of both treatments. Prospective trials are currently evaluating these hypotheses and will ultimately serve to optimize immunotherapy in the treatment of prostate cancer.


Positive and negative regulation of transcription in vitro: enhancer-binding protein AP-2 is inhibited by SV40 T antigen.
We have purified a 52 kd protein, AP-2, that binds to enhancer regions of SV40 and human metallothionein IIA (hMT IIA) and stimulates RNA synthesis from these promoters in vitro. Surprisingly, AP-2 also binds to two SV40 early promoter regions recognized by Sp1 and T antigen. Juxtaposed binding sites for AP-2 and Sp1 in the 21 bp repeats may facilitate productive interactions between the two factors. In contrast, sequence-specific binding of AP-2 to SV40 and hMT IIA DNA is inhibited by the viral repressor protein T antigen. Furthermore, T antigen inhibits AP-2-dependent transcriptional activation of the hMT IIA promoter in vitro. The inhibition is neither a direct nor an indirect result of T antigen binding to DNA, because the hMT IIA promoter lacks T antigen binding sites. Instead, sedimentation studies suggest that protein-protein interactions between AP-2 and T antigen block AP-2 binding to DNA. These findings suggest novel mechanisms for mediating positive and negative regulation of transcription.


Lymphatics in the alimentary tract of children in health and disease: study on mucosal biopsies using the monoclonal antibody d2-40.
Primary intestinal lymphangiectasia and intestinal lymphatic hypoplasia are 2 causes of protein-losing enteropathy in children and share many common clinical features. For the diagnosis of lymphatic hypoplasia on endoscopic biopsies of the intestine, i.e., based on a negative finding in a small specimen, a very sensitive and specific method for identifying lymphatics is essential. In the present study, lymphatic vessels were labelled using D2-40 immunostaining in mucosal biopsy specimens of the alimentary tract of children in whom no histologic abnormality was noted and of those who had different relatively common pediatric conditions, including inflammatory and neoplastic diseases. Using this method, lymphatic vessels were well visualized even in young infants and not destroyed by diseases. The presence of the muscularis mucosae in specimens was important for adequate assessment. In the duodenum and esophagus, lymphatics were observed in every single section; in the stomach, ileum, and colon, they were less regular and several sections were sometimes required. The extreme sensitivity of this method for demonstrating lymphatic vessels in the duodenum makes it ideal for the histologic diagnosis of intestinal lymphatic hypoplasia. In 4 patients who were considered to have this diagnosis based on clinical features, full-thickness intestinal biopsies and electron microscopy, D2-40 immunostaining confirmed the absence or marked paucity of lymphatics.


Nanoscale Relative Emission Efficiency Mapping Using Cathodoluminescence g(2) Imaging.
Cathodoluminescence (CL) imaging spectroscopy provides two-dimensional optical excitation images of photonic nanostructures with a deep-subwavelength spatial resolution. So far, CL imaging was unable to provide a direct measurement of the excitation and emission probabilities of photonic nanostructures in a spatially resolved manner. Here, we demonstrate that by mapping the cathodoluminescence autocorrelation function g(2) together with the CL spectral distribution the excitation and emission rates can be disentangled at every excitation position. We use InGaN/GaN quantum wells in GaN nanowires with diameters in the range 200-500 nm as a model system to test our new g(2) mapping methodology and find characteristic differences in excitation and emission rates both between wires and within wires. Strong differences in the average CL intensity between the wires are the result of differences in the emission efficiencies. At the highest spatial resolution, intensity variations observed within wires are the result of excitation rates that vary with the nanoscale geometry of the structures. The fact that strong spatial variations observed in the CL intensity are not only uniquely linked to variations in emission efficiency but also linked to excitation efficiency has profound implications for the interpretation of the CL data for nanostructured geometries in general.


Diabetes alert study: weight history and upper body obesity in diabetic and non-diabetic Mexican American adults.
History of adult weight gain and fat patterning is compared in Mexican American diabetics and age and sex matched non-diabetics. Diabetics differed little from non-diabetics in overall body fatness at the time of the examination. However, history of adult weight gain and current fat patterning were very different. Diabetics were heavier than non-diabetics at age 18. They subsequently gained weight faster and attained a substantially higher weight, at an earlier age, than non-diabetics. Discriminant function analysis was used to test for differences in patterning. Diabetics tend to have more trunk fat, as reflected particularly in the subscapular skinfold, and less lower extremity (leg) fat. Fat patterning in this population does not appear to be influenced by age when weight gain occurred, but is related to diabetic status, especially in women.


The measurement of reticular basement membrane and submucosal collagen in the asthmatic airway.
An increase in types III and V collagen below the bronchial epithelium of the airway is known to be responsible for apparent thickening of the reticular basement membrane (RBM) and is recognized as a characteristic feature of asthma. Wide variations exist in reported ranges of the thickness of the RBM in both asthmatic and control airways. The description of collagen deposition has been confined to the RBM with no previous reports of increased collagen deeper within the bronchial wall (i.e. submucosa), although inflammation is known to extend to deeper levels. The objective of this study was to compare different methods used to measure RBM thickness and to examine collagen deposition in deeper asthmatic bronchial submucosa. We examined bronchial mucosal biopsies from 15 asthmatic and 13 normal healthy controls to measure RBM thickness by light and electron microscopic methods on resin sections and to estimate the extent of collagen deposition in the submucosa by immunochemical staining with monoclonal antibodies to collagen subtypes on paraffin sections. Simple staining with toluidine blue on resin sections coupled with light microscopic evaluation was as accurate and less expensive than electron microscopic methods in the measurement of the thickness of RBM (mean +/- SD, light microscopy: asthma vs control, 6.01 +/- 2.09 vs 3.19 +/- 0.55 microns, P < 0.001; electron microscopy: asthma vs control, 6.09 +/- 2.19 vs 2.85 +/- 0.86 microns, P < 0.01). Using monoclonal antibodies to collagen subtypes and image analysis methods, we identified increased collagen in the submucosa in asthma (type III collagen, asthma vs control: 62 +/- 7 vs 51 +/- 9%, P < 0.05, type V collagen, asthma vs control: 60 +/- 6 vs 52 +/- 9%, P < 0.05). This study has demonstrated that the RBM may be reliably measured by light microscopic methods. This study shows for the first time that the submucosa of the asthmatic airway contains significantly more collagen than normal controls, giving rise to the possibility that airway scar formation may have greater functional implications than has been previously believed from consideration of the RBM alone.


MLGA--a rapid and cost-efficient assay for gene copy-number analysis.
Structural variation is an important cause of genetic variation. Whole genome analysis techniques can efficiently identify copy-number variable regions but there is a need for targeted methods, to verify and accurately size variable regions, and to diagnose large sample cohorts. We have developed a technique based on multiplex amplification of size-coded selectively circularized genomic fragments, which is robust, cheaper and more rapid than current multiplex targeted copy-number assays.


Helium inhalation in adolescents: characteristics of users and prevalence of use.
Although helium-related fatalities and concerns about potentially harmful effects of helium use have increased in recent years, virtually nothing is known about the epidemiology of helium inhalation in adolescents. This exploratory investigation examined the prevalence and correlates of helium inhalation in a large sample of at-risk youth. Study participants were 723 Missouri adolescents (M age = 15.5, SD = 1.2) in residential treatment for delinquent behavior. More than one-in-nine (N = 81, 11.5%) adolescents had inhaled helium with the intention of getting high, and one-third (N = 27, 34.2%) of helium users reported they actually did get high when they inhaled helium. Helium users were significantly more likely to be Caucasian, to live in rural/small town areas, and to have histories of mental illness, auditory hallucinations, and alcohol and marijuana use than nonusers. Helium users also reported significantly more current psychiatric distress, suicidality, traumatic life experiences, and antisocial attitudes, traits, and behaviors than nonusers. Helium inhalation was prevalent in this sample and many such users reported getting high while using helium. Helium users had psychosocial profiles similar to those of volatile solvent users, suggesting that they may be at substantial risk for a variety of adverse health outcomes.


Gain of function mutation in the mineralocorticoid receptor of the Brown Norway rat.
The aim of this research was to identify the molecular bases of differences in sensitivity to corticosteroid hormones between Brown Norway and Fischer 344 rats. We previously showed an apparent insensitivity to adrenalectomy in Brown Norway rats. Based on our first hypothesis of a different activity/reactivity of the mineralocorticoid signaling pathway between the two rat strains, we sequenced Brown Norway and Fischer 344 mineralocorticoid receptor cDNA and identified a tyrosine to cysteine substitution (Y73C) in the N-terminal part of the Brown Norway mineralocorticoid receptor. As a first step, this substitution gave us a means to distinguish the Brown Norway allele from the Fischer 344 at the mineralocorticoid receptor locus in an F2 population. We showed a strong genetic linkage between the mineralocorticoid receptor genotype and sensitivity to adrenalectomy. A subsequent genome-wide linkage analysis confirmed the involvement of the mineralocorticoid receptor locus and implicated other loci, including one on chromosome 4, which collectively explain a large part of the strain differences in corticosteroid receptor responses. In vitro studies further revealed that the Y73C substitution induces greater transactivation of the mineralocorticoid receptor by aldosterone, and surprisingly by progesterone as well, which could substitute for aldosterone after adrenalectomy in Brown Norway rats. We challenged this hypothesis in vivo and showed that plasma progesterone is higher in Brown Norway male rats and partially compensates for aldosterone after adrenalectomy. This work illustrates the interest of a pluristrategic approach to explore the mineralocorticoid receptor signaling pathway and its implication in the regulation of hydroelectrolytic homeostasis and blood pressure.


Histamine release from isolated and intact mast cells of rats.
The release of histamine from tissues of rats, induced by antigen, concanavalin A and dextran has been compared with that from isolated peritoneal mast cells. Whereas concanavalin A was more active than dextran in in vitro experiments, the reverse was found when the substances were injected intradermally into the skin or subcutaneously into the paw. Therefore, it is important to state the experimental conditions when comparisons of activities of histamine releasers are made.


Commercial massage tool-induced spinal epidural hematoma.
Spinal epidural hematoma (SEH), which may develop into an emergency condition, is a rare disease. Here, we present the case of a patient with SEH caused by cervical massage using a commercial massage tool. A 75-year-old man was brought to our hospital with a chief complaint of posterior neck pain during sleep. He had used a commercial massage tool before going to bed. Upon arrival, hypotension and respiratory failure were observed. His muscle strength in both the upper and lower extremities rated 0 on the manual muscle test, and sensory loss below the papillae was observed. His symptoms resolved spontaneously after 2 h. Magnetic resonance imaging suggested a spinal cord epidural hematoma at the C2/C3 to C3/C4 level. On day 6, the patient was discharged without any impairment. Fatal complications could occur by cervical massage using a commercial massage tool.


Amrinone improves survival in hemorrhagic shock.
Amrinone is a noncatecholamine inotropic agent used clinically in the management of heart failure. The purpose of this study was to determine if intravenous (i.v.) infusion of amrinone has beneficial effects during resuscitation from experimental hemorrhagic shock. Effectiveness was defined as significantly improved survival rate. Mean arterial pressure (MAP) and tissue oxygen tension (pO2) were measured to assess the physiologic effects of amrinone. Two separate randomized and blinded survival trials were conducted. In each trial, rats were randomly assigned to either a control group (n = 10) or an experimental group (n = 10). All animals were bled 27 ml/kg over 2 minutes and maintained in shock for 45 minutes before resuscitation. Resuscitation in placebo (control) animals was with 54 ml/kg (2 times the hemorrhage volume) Lactated Ringer's solution over 1 hour, whereas resuscitation in drug-treated animals was with a 0.75 mg/kg bolus amrinone over 3 minutes followed by 54 ml/kg Lactated Ringer's solution and 5 ug/kg/min infusion over 1 hour. Results were that resuscitation with amrinone significantly increased MAP, tissue pO2, and survival over resuscitation with Lactated Ringer's alone (P < 0.05). In both trials, survival rates increased by more than 66 per cent in the amrinone groups.


Inner Phases of Colloidal Hexagonal Spin Ice.
Using numerical simulations that mimic recent experiments on hexagonal colloidal ice, we show that colloidal hexagonal artificial spin ice exhibits an inner phase within its ice state that has not been observed previously. Under increasing colloid-colloid repulsion, the initially paramagnetic system crosses into a disordered ice regime, then forms a topologically charge ordered state with disordered colloids, and finally reaches a threefold degenerate, ordered ferromagnetic state. This is reminiscent of, yet distinct from, the inner phases of the magnetic kagome spin ice analog. The difference in the inner phases of the two systems is explained by their difference in energetics and frustration.


Hepatic stellate cell-intrinsic role of SOCS1 in controlling hepatic fibrogenic response and the pro-inflammatory macrophage compartment during liver fibrosis.
Hepatic stellate cells (HSC) become activated, differentiate to myofibroblasts and produce extracellular fibrillar matrix during liver fibrosis. The hepatic fibrogenic response is orchestrated by reciprocal interactions between HSCs and macrophages and their secreted products. SOCS1 can regulate several cytokines and growth factors implicated in liver fibrosis. Here we investigated the role of SOCS1 in regulating HSC activation. Mice lacking SOCS1 in HSCs (Socs1ΔHSC) were generated by crossing Socs1fl/fl and LratCre mice. Liver fibrosis was induced by carbon tetrachloride and evaluated by Sirius red staining, hydroxyproline content and immunostaining of myofibroblasts. Gene expression of pro-fibrogenic factors, cytokines, growth factors and chemokines were quantified by RT-qPCR. The phenotype and the numbers of intrahepatic leukocyte subsets were studied by flow cytometry. The impact of fibrosis on the development of diethyl nitrosamine-induced hepatocellular carcinoma was evaluated. Socs1ΔHSC mice developed more severe liver fibrosis than control Socs1fl/fl mice that was characterized by increased collagen deposition and myofibroblast differentiation. Socs1ΔHSC mice showed a significant increase in the expression of smooth muscle actin, collagens, matrix metalloproteases, cytokines, growth factors and chemokines in the liver following fibrosis induction. The fibrotic livers of Socs1ΔHSC mice displayed heightened inflammatory cell infiltration with increased proportion and numbers of Ly6ChiCCR2+ pro-inflammatory macrophages. This macrophage population contained elevated numbers of CCR2+CX3CR1+ cells, suggesting impaired transition towards restorative macrophages. Fibrosis induction following exposure to diethyl nitrosamine resulted in more numerous and larger liver tumor nodules in Socs1ΔHSC mice than in Socs1fl/fl mice. Our findings indicate that (i) SOCS1 expression in HSCs is a critical to control liver fibrosis and development of hepatocaellular carcinoma, and (ii) attenuation of HSC activation by SOCS1 regulates pro-inflammatory macrophage recruitment and differentiation during liver fibrosis.


Observation of a chloride-dependent intermediate during catalysis by angiotensin converting enzyme using radiationless energy transfer.
Stopped-flow radiationless energy-transfer kinetics have been used to examine the effects of chloride on the hydrolysis of Dns-Lys-Phe-Ala-Arg by angiotensin converting enzyme. The kinetic constants for hydrolysis at pH 7.5 and 22 degrees C in the presence of 300 mM sodium chloride were KM = 28 microM and kcat = 110 s-1, and in its absence, KM = 240 microM and kcat = 68 s-1. The apparent binding constant for chloride was 4 mM, and the extent of chloride activation in terms of kcat/KM was 14-fold. The effects of chloride on the pre-steady-state were examined at 2 degrees C. In the presence of chloride, two distinct enzyme-substrate complexes were observed, suggesting multiple steps in substrate binding. The initial complex was formed during the mixing period (kobsd greater than 200 s-1) while the second complex was formed much more slowly (kobsd = 40 s-1 when [S] = 5 microM and [NaCl] = 150 mM). Strikingly, in the absence of chloride, only a single, rapidly formed enzyme-substrate complex was observed. These results are consistent with a nonessential activator kinetic mechanism in which the slow step reflects conversion of an initially formed complex, (E X Cl- X S)1, to a more tightly bound complex, (E X Cl- X S)2.


Poor results of the cementless total hip arthroplasty with a nonporous coated acetabular component: AcSys Shearer Cup.
This study followed patients for a minimum of 7 years after primary total hip arthroplasty using cementless acetabular components and evaluated their outcomes. We followed 73 patients (75 hips), who had undergone total hip arthroplasty with cementless nonporous coated acetabular components (3M AcSys Shearer Cup) for a mean of 9.8 years (range 7-13 years). There were 61 women and 12 men with a mean age of 53 years (range 27-69 years) at surgery. The diagnosis was primary osteoarthritis in 9 hips, osteoarthritis secondary to developmental dysplasia in 58 hips, osteonecrosis of the femoral head in 6 hips, and rheumatoid arthritis in 2 hips. Three cups were revised because of aseptic loosening, and one cup was revised following removal of the prosthesis due to deep infection. Radiographic loosening was observed in 22 hips at the latest follow-up. The survival rate at 10 years was 94.7% with revision as the endpoint and 72% with radiographic loosening as the endpoint. The Merle d'Aubigné and Postel hip score showed significant improvement postoperatively and was maintained well even in cases showing radiographic loosening. The intermediate radiological results with the AcSys Shearer Cup were unsatisfactory because of the high loosening rate, although the revision rate was low. The nonporous outer surface and the poor fixation mechanism between the metal shell and liner may have contributed to the high failure rate. Regular radiological review is recommended when this cup is used because early loosening is often painless.


Population genetic structure of Patagonian toothfish (Dissostichus eleginoides) in the Southeast Pacific and Southwest Atlantic Ocean.
Previous studies of population genetic structure in Dissostichus eleginoides have shown that oceanographic and geographic discontinuities drive in this species population differentiation. Studies have focused on the genetics of D. eleginoides in the Southern Ocean; however, there is little knowledge of their genetic variation along the South American continental shelf. In this study, we used a panel of six microsatellites to test whether D. eleginoides shows population genetic structuring in this region. We hypothesized that this species would show zero or very limited genetic structuring due to the habitat continuity along the South American shelf from Peru in the Pacific Ocean to the Falkland Islands in the Atlantic Ocean. We used Bayesian and traditional analyses to evaluate population genetic structure, and we estimated the number of putative migrants and effective population size. Consistent with our predictions, our results showed no significant genetic structuring among populations of the South American continental shelf but supported two significant and well-defined genetic clusters of D. eleginoides between regions (South American continental shelf and South Georgia clusters). Genetic connectivity between these two clusters was 11.3% of putative migrants from the South American cluster to the South Georgia Island and 0.7% in the opposite direction. Effective population size was higher in locations from the South American continental shelf as compared with the South Georgia Island. Overall, our results support that the continuity of the deep-sea habitat along the continental shelf and the biological features of the study species are plausible drivers of intraspecific population genetic structuring across the distribution of D. eleginoides on the South American continental shelf.


Epidemiology of epilepsy surgery in India.
Epilepsy surgery in India has seen remarkable advances over the last twenty years. Presently 39 centers are undertaking epilepsy surgeries in India on a regular basis. Out of these, 18 centers have become operational in the last five years. Many of them are well equipped with high end technologies and have expertise to undertake all kinds of epilepsy surgeries. Till July 31st, 2016, approximately 7143 epilepsy surgeries have been performed in India. Presently, 734 epilepsy surgeries are carried out in India every year representing an increase of approximately 58% over the last three and a half years as compared to the previous years. The reported postoperative outcomes from all these centers are comparable to those reported from the well-established centers in high income countries. Still, only 2 in 1000 eligible patients In India undergo epilepsy surgery, because of which, the enormous surgical treatment gap continues to persist. To tackle this, by the year 2020, India should have at least 60 state-level epilepsy surgery centers (with each undertaking at least 50 surgeries per year) and 6 national centers of excellence. Here, we discuss the current prevalence and practice of epilepsy surgery in India and suggest pragmatic steps and solutions to make epilepsy surgery affordable and widely available. The steps also include a framework for the development of a national epilepsy surgery program.


Adaptive responses to cefotaxime treatment in ESBL-producing Escherichia coli and the possible use of significantly regulated pathways as novel secondary targets.
The aim of the study was to determine how ESBL-producing Escherichia coli change the expression of metabolic and biosynthesis genes when adapting to inhibitory concentrations of cefotaxime. Secondly, it was investigated whether significantly regulated pathways constitute putative secondary targets that can be used to combat the resistant bacteria. Strains of E. coli MG1655 encoding blaCTX-M-1 from an IncI1 plasmid and from the chromosome were challenged with cefotaxime corresponding to inhibitory concentrations, and transcriptional patterns were compared with growth without or with very low concentrations of cefotaxime by RNA sequencing. Significantly regulated pathways were inhibited with suitable inhibitors, or genes encoding the enzymes of the regulated pathways were knocked out. The ability of the bacteria to grow in the presence of cefotaxime was determined. Chequerboard assays were utilized to confirm synergies between treatments. Genes belonging to 16 different functional gene classes were significantly regulated. Protein and peptidoglycan syntheses were up-regulated and low concentrations of chloramphenicol or d-cycloserine, targeting these systems, strongly reduced the MIC of cefotaxime (>32-fold). Inhibition and/or mutations in other genes that were significantly regulated, belonging to energy synthesis, purine synthesis, proline uptake or potassium uptake, also rendered the resistant bacteria more susceptible to cefotaxime. The results show that ESBL-producing E. coli adapt to treatment with cefotaxime by changing their gene expression patterns and furthermore that targeting regulated adaptive pathways may be a suitable way to identify targets for drugs that will specifically inhibit the resistant bacteria.


Biomarker-Guided Versus Guideline-Based Treatment of Patients With Heart Failure: Results From BIOSTAT-CHF.
Heart failure guidelines recommend up-titration of angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) to doses used in randomized clinical trials, but these recommended doses are often not reached. Up-titration may, however, not be necessary in all patients. This study sought to establish the role of blood biomarkers to determine which patients should or should not be up-titrated. Clinical outcomes of 2,516 patients with worsening heart failure from the BIOSTAT-CHF (BIOlogy Study to Tailored Treatment in Chronic Heart Failure) were compared between 3 theoretical treatment scenarios: scenario A, in which all patients are up-titrated to >50% of recommended doses; scenario B, in which patients are up-titrated according to a biomarker-based treatment selection model; and scenario C, in which no patient is up-titrated to >50% of recommended doses. The study conducted multivariable Cox regression using 161 biomarkers and their interaction with treatment, weighted for treatment-indication bias to estimate the expected number of deaths or heart failure hospitalizations at 24 months for all 3 scenarios. Estimated death or hospitalization rates in 1,802 patients with available (bio)markers were 16%, 16%, and 26%, respectively, in the ACE inhibitor/ARB up-titration scenarios A, B, and C. Similar rates for beta-blocker and MRA up-titration scenarios A, B, and C were 23%, 19%, and 24%, and 12%, 11%, and 24%, respectively. If up-titration was successful in all patients, an estimated 9.8, 1.3, and 12.3 events per 100 treated patients could be prevented at 24 months by ACE inhibitor/ARB, beta-blocker, and MRA therapy, respectively. Similar numbers were 9.9, 4.7, and 13.1 if up-titration treatment decision was based on a biomarker-based treatment selection model. Up-titrating patients with heart failure based on biomarker values might have resulted in fewer deaths or hospitalizations compared with a hypothetical scenario in which all patients were successfully up-titrated.


Reference values for amino acids and acylcarnitines in peripheral blood in Quarter horses and American Miniature horses.
Free amino acids and acylcarnitines circulating in the blood can be used for diagnosis for metabolic illness and imbalances. To date, the normal reference ranges of amino acids and acylcarnitines in horse peripheral blood have not been established. In this study, the concentrations of 12 amino acids and 26 acylcarnitines were determined by tandem mass spectrometry in complete blood from 100 healthy horses (50 Quarter horses (QH) [23 males and 27 females] and 50 American Miniature horses (AMH) [15 males and 35 females]) with no signs of metabolic disease. The means and standard deviations were determined and data statistically analyzed. Concentrations of short, medium, and long chain acylcarnitines were significantly higher in male AMH than in male QH. The concentrations of the amino acids alanine, arginine, glycine, proline (glycogenic), and leucine (ketogenic) were higher in the QH than in the AMH. Female AMH had higher concentrations of propionylcarnitine, leucine, proline, arginine, and ornithine than female QH. Normal reference ranges of amino acids and acylcarnitines were established for AMH and QH. Significant differences were found in concentration of these compounds between breeds and gender.


Serologic characteristics in primary biliary cirrhosis associated with sicca syndrome.
Patients with primary biliary cirrhosis (PBC) may have coincidental sicca syndrome (SS). The frequencies of SS and the occurrence of the Sjögren's-associated anti-Ro and -La antibodies in PBC patients have been reported at widely varying prevalences. This study investigated whether distinctive serologic characteristics are associated with SS in PBC. Forty PBC patients and thirty patients with other types of liver cirrhosis were tested for SS and associated autoantibodies (ANA, AMA 2, anti-Ro, anti-La, anti-U1RNP-A, -C, -68 kD, and rheumatoid factors). Fourteen PBC patients (35%) complained of sicca symptoms, of whom 10 (25%) had a positive Schirmer-I test, and 7 (17.5%) had serologic characteristics similar to those of Sjögren's syndrome. Anti-52-kD Ro antibodies were positive in seven PBC/SS cases (p < 0.025). There was no anti-Ro positive PBC patient without SS. Three patients with PBC/SS with anti-52-kD Ro and anti-smooth-muscle antibodies developed lung fibrosis. No patient in the other cirrhosis group had SS or its characteristic autoantibody findings. It was suggested that PBC and SS are frequently associated. Anti-52-kD Ro antibodies seem to be a characteristic serologic finding for SS in PBC, suggesting their pathogenic role in autoimmune sialadenitis.


Two-port laparoscopic appendectomy assisted with needle grasper comparison with conventional laparoscopic appendectomy.
The 2-port laparoscopic appendectomy technique (TLA) is between the conventional 3-port and single-port laparoscopic appendectomy surgeries. We compared postoperative pain and cosmetic results after TLA with conventional laparoscopic appendectomy (CLA) by a 3-port device. Patients undergoing TLA were matched with patients undergoing CLA between February 2015 and November 2015 at the same institution. Thirty-two patients underwent TLA with a needle grasper. The appendix was secured by a percutaneous organ-holding device (needle grasper), then removed through a puncture at McBurney's point. Another 38 patients underwent CLA. Patient demographics, operative details, and postoperative outcomes were collected and evaluated. One patient in the TLA group developed a wound infection and 1 patient in the CLA group developed a postoperative intra-abdominal abscess and 3 wound infections. There was no significant difference between the groups when comparing the length of hospital stay, time until oral intake, and other complications. The pain score in the first 12 hours after surgery was significanly higher in CLA group than the TLA group (P < 0.001). Operative time was significantly shorter in the CLA group compared to the TLA group (P < 0.001). TLA using a needle grasper was associated with a significantly lower pain score 12 hours after surgery, better cosmetic results, and lower cost, than the CLA 3-port procedure because of the fewer number of ports.


ExtRanFS: An Automated Lung Cancer Malignancy Detection System Using Extremely Randomized Feature Selector.
Lung cancer is an abnormality where the body's cells multiply uncontrollably. The disease can be deadly if not detected in the initial stage. To address this issue, an automated lung cancer malignancy detection (ExtRanFS) framework is developed using transfer learning. We used the IQ-OTH/NCCD dataset gathered from the Iraq Hospital in 2019, encompassing CT scans of patients suffering from various lung cancers and healthy subjects. The annotated dataset consists of CT slices from 110 patients, of which 40 were diagnosed with malignant tumors and 15 with benign tumors. Fifty-five patients were determined to be in good health. All CT images are in DICOM format with a 1mm slice thickness, consisting of 80 to 200 slices at various sides and angles. The proposed system utilized a convolution-based pre-trained VGG16 model as the feature extractor and an Extremely Randomized Tree Classifier as the feature selector. The selected features are fed to the Multi-Layer Perceptron (MLP) Classifier for detecting whether the lung cancer is benign, malignant, or normal. The accuracy, sensitivity, and F1-Score of the proposed framework are 99.09%, 98.33%, and 98.33%, respectively. To evaluate the proposed model, a comparison is performed with other pre-trained models as feature extractors and also with the existing state-of-the-art methodologies as classifiers. From the experimental results, it is evident that the proposed framework outperformed other existing methodologies. This work would be beneficial to both the practitioners and the patients in identifying whether the tumor is benign, malignant, or normal.


Spent coffee grounds as a versatile source of green energy.
The production of energy from renewable and waste materials is an attractive alternative to the conventional agricultural feed stocks such as corn and soybean. This paper describes an approach to extract oil from spent coffee grounds and to further transesterify the processed oil to convert it into biodiesel. This process yields 10-15% oil depending on the coffee species (Arabica or Robusta). The biodiesel derived from the coffee grounds (100% conversion of oil to biodiesel) was found to be stable for more than 1 month under ambient conditions. It is projected that 340 million gallons of biodiesel can be produced from the waste coffee grounds around the world. The coffee grounds after oil extraction are ideal materials for garden fertilizer, feedstock for ethanol, and as fuel pellets.


Urea sensor with single poly(propylene) membrane.
Urease was immobilized on the plasma-aminated surface of a hyfrophobic poly(propylene) (PP) membrane. This membrane, with urease matrix on one side while maintaining its original hydrophobic property on the other, was used to construct the urea sensor. The new urea sensors had response sensitivities ranged from 19 mV/decade to 30 mV/decade depending on the conditions of the plasma reaction. The enzyme electrode using single membrane gave a shorter response time as compared to the corresponding conventional electrode employing two separate PP membranes. The sensitivity of the enzyme electrode increased with increasing buffer pH and reached a maximal level (40 mV/decade) at pH 7.6. The response sensitivity of the electrode was not affected by the change of buffer strength. Deamination of the plasma-modified hydrophobic PP membrane did not occur in aqueous environment judging from the stability of the urea electrode up to 12 days of operation.


VEGAS2: Software for More Flexible Gene-Based Testing.
Gene-based tests such as versatile gene-based association study (VEGAS) are commonly used following per-single nucleotide polymorphism (SNP) GWAS (genome-wide association studies) analysis. Two limitations of VEGAS were that the HapMap2 reference set was used to model the correlation between SNPs and only autosomal genes were considered. HapMap2 has now been superseded by the 1,000 Genomes reference set, and whereas early GWASs frequently ignored the X chromosome, it is now commonly included. Here we have developed VEGAS2, an extension that uses 1,000 Genomes data to model SNP correlations across the autosomes and chromosome X. VEGAS2 allows greater flexibility when defining gene boundaries. VEGAS2 offers both a user-friendly, web-based front end and a command line Linux version. The online version of VEGAS2 can be accessed through https://vegas2.qimrberghofer.edu.au/. The command line version can be downloaded from https://vegas2.qimrberghofer.edu.au/zVEGAS2offline.tgz. The command line version is developed in Perl, R and shell scripting languages; source code is available for further development.


Treatment of colon cancer cells with 5-fluorouracil can improve the effectiveness of RNA-transfected antitumor dendritic cell vaccine.
Non-cytotoxic concentrations of selected chemotherapeutic agents amplify the antigen presentation capacity of dendritic cells (DCs) and are able to increase the immunogenicity of the colon cancer cell lineage HCT‑116, as previously demonstrated by our group. Since this functional alteration was associated with changes in gene expression, we aimed to evaluate whether transcriptional changes of tumor cells can be transferred to DCs, increasing their ability to induce a specific antitumor response. Therefore, HCT‑116 cells were treated with two different concentrations of 5-fluorouracil (5-FU), and their total RNA was transfected into human monocyte-derived DC, which function was evaluated through their ability to stimulate the proliferation of normal allogeneic T lymphocytes (MLR), and to generate cytolytic T cells. The transfected DCs demonstrated an increased percentage of CD83+, HLA-DR+, CD80+ and CD86+ cells. These phenotypical changes were followed by functional improvement demonstrated by the increased capacity of these DC to induce allogeneic T cell proliferation and to generate specific anti-HCT‑116 cytolytic T cells, as demonstrated by IFN-γ production following in vitro challenge with tumor cells. Our results allow us to conclude that treatment of tumor cells with a non-toxic concentration of 5-FU induces immunogenic changes that are transferred to DC by transfection of total RNA.