Investigation of the clinical features of geographic tongue: unveiling its relationship with oral psoriasis.
Few studies have examined the clinical features of geographic tongue (GT), an inflammatory lesion, making diagnosis and the investigation of oral psoriasis difficult. To investigate the clinical features of GT to facilitate its identification and understand its relationship with psoriasis. A total of 96 participants diagnosed with GT underwent stomatological and dermatological examinations. The parameters assessed were burning sensation; number, classification, and location of lesions; loss of papillae; severity of GT lesions; and association with fissured tongue (FT). Psoriatic patients (PS) and those without psoriasis (NPS) were compared. Burning sensation was reported by 45 (47%) patients, 67 (70%) patients showed active GT, 68 (71%) presented with typical lesions, and 59 (61%) exhibited moderate lesions. GT was associated with FT in 75% of the cases and exhibited a diffused pattern associated with severe lesions. It was also more frequent in the PS group. The comparative analysis between the PS and NPS groups showed significant differences between the groups with regard to gender, presence of burning sensation, and GT severity. GT is a symptomatic lesion with a thick halo. In contrast, psoriatic patients are frequently asymptomatic and exhibit severe lesions with greater loss of papillae that are associated with severe FT. The present study is the first to demonstrate clinical differences in the GT of patients with and without psoriasis, suggesting that some GT cases may represent true oral psoriasis and some cases may represent only GT.


Isl1Cre reveals a common Bmp pathway in heart and limb development.
A number of human congenital disorders present with both heart and limb defects, consistent with common genetic pathways. We have recently shown that the LIM homeodomain transcription factor islet 1 (Isl1) marks a subset of cardiac progenitors. Here, we perform lineage studies with an Isl1Cre mouse line to demonstrate that Isl1 also marks a subset of limb progenitors. In both cardiac and limb progenitors, Isl1 expression is downregulated as progenitors migrate in to form either heart or limb. To investigate common heart-limb pathways in Isl1-expressing progenitors, we ablated the Type I Bmp receptor, Bmpr1a utilizing Isl1Cre/+. Analysis of consequent heart and limb phenotypes has revealed novel requirements for Bmp signaling. Additionally, we find that Bmp signaling in Isl1-expressing progenitors is required for expression of T-box transcription factors Tbx2 and Tbx3 in heart and limb. Tbx3 is required for heart and limb formation, and is mutated in ulnar-mammary syndrome. We provide evidence that the Tbx3 promoter is directly regulated by Bmp Smads in vivo.


Talking to dying patients of their hopes and needs.
Patients use many different coping mechanisms when they are facing a terminal diagnosis, but it should not be assumed that they want to talk to nurses about the terminal nature of their illness. Research shows that a proportion of patients may want to, so this article suggests that best practice with regard to communication in palliative care could be achieved by using a sensitive assessment of how each patient chooses to cope with his or her situation rather than a uniform approach to care.


A case of Histoplasma capsulatum causing granulomatous liver disease and Addisonian crisis.
A 56-year-old man with persistently elevated liver enzyme levels, fatigue, lethargy and a 9.0 kg weight loss over six months underwent a percutaneous liver biopsy that demonstrated multiple granulomas. Screening serologies were positive for histoplasmosis, and he was started on itraconazole treatment. He returned to hospital the same night with coffee-ground emesis and in Addisonian crisis requiring parenteral steroids and intensive care unit support. An abdominal computed tomography scan revealed bilaterally enlarged, nonenhancing adrenal glands suggestive of infarcts, presumed secondary to histoplasmosis. Treatment was initiated with amphotericin B, and Histoplasma capsulatum was cultured from his urine and cerebrospinal fluid. A serum immunodiffusion test was also positive for both H and M bands, indicating active infection with Histoplasmosis species. His serum and urine samples were also weakly positive for the antigen. Despite complications of renal failure, pneumonia and congestive heart failure, he recovered with medical therapy and was discharged home to complete a prolonged course of itraconazole therapy. While hepatic granulomas often reflect an occult disease process, the cause may remain undiscovered in 30% to 50% of patients despite exhaustive investigations. H capsulatum is an uncommon cause of granulomatous liver disease, and with its protean clinical presentation, a high index of suspicion is needed to make the diagnosis and avoid the potentially high fatality rate associated with disseminated infection.


Control of Reactive Power with Genetic Algorithm in Electrical Power Systems with Photovoltaic Power Plant.
The present paper has as its objective to optimize the reactive power in electric systems that have a photovoltaic power plant connected to it, thus aiming at improving the voltage profile of all system buses, so that they meet the values determined in the standard. For this, it is proposed to accurately determine the ideal amount of reactive power, using the genetic algorithm, in which there is no use of approximate equations, reduction of the active power of the photovoltaic source and, moreover, it allows the regulation of the voltage of all the buses in the system, being able to raise or reduce their voltage level. The proposed methodology is validated through the analysis of the 14-bus electric system from IEEE, into which a photovoltaic power plant was connected. Studies were carried out with six different load scenarios in the literature to observe the performance of the proposed algorithm. Through the analysis of the results, one concludes that the developed genetic algorithm is efficient for determining the reactive power values that result in the reduction or increase of the voltage levels of all buses in the system, allowing them to meet the values determined in the regulatory standards.


Effect of early plasmapheresis and immunosuppressive therapy on natural history of anti-glomerular basement membrane glomerulonephritis: report of a 22-month follow-up.
A patient with anti-glomerular basement membrane (GBM)-mediated necrotizing and proliferative glomerulonephritis with crescents was treated with plasmapheresis, cyclophosphamide, and steroids. Treatment resulted in decreased circulating anti-GBM antibody and prompt improvement of renal function that remained stable for 15 months after all treatment was discontinued. Renal biopsies were performed initially, at seven and 17 months. Immunofluorescent examination showed that anti-GBM antibody continued to be present on GBMs although light and electron microscopic findings demonstrated a transformation to a form of sclerosing glomerulonephritis. To our knowledge, this patient's course is the first demonstration that early treatment with plasmapheresis and immunosuppressions may transform the histologic findings in anti-GBM-induced rapidly progressive glomerulonephritis, thereby altering the natural history of this disease.


Facile fabrication of hypercrosslinked microporous polymer nanospheres for effective inhibition of triple negative breast cancer cells proliferation.
Treatment failure is one of the main lethal causes of human triple negative breast cancer (TNBC) patients due to inefficient drug administration. The present study demonstrated the development of functional microporous organic polymers (MOPs) as a potential drug carrier and its controlled release. Due to the existence of abundant pores and high surface area, MOPs have promoted the high drug payloads, facilitating prolonged retention time and improved drug release. Herein, porous organic polymer has been fabricated via knitting strategy using the carbonyl bridged external crosslinker. Utilizing the imine chemistry, post-functionalization at the bridging carbon with the diamine resulted in the functional porous framework which had been further modified with single stranded DNA (ssDNA). Due to the conjugated structure, the designed material incorporates the strong blue fluorescence that assists in bio-imaging. In short, the inherent features of hypercrosslinked microporous polymers nanospheres (HMPNs) enabled the high encapsulation of Epirubicin (EPI) and its controlled release in TNBC cell lines (SUM-159 and MDA-MB-231) to inhibit cancer cells proliferation. We anticipate that the further development in functionalization of hypercrosslinked polymers may lead to a breakthrough in biomedical applications.


Cerebellar involvement in timing accuracy of rhythmic finger movements in essential tremor.
The cerebellum is involved in the generation of essential tremor (ET) and cerebellar timing function is altered in patients with ET showing an increased variability of rhythmic hand movements. Using a sensor-engineered glove, we evaluated motor behaviour during repetitive finger tapping movements in 15 patients with ET and in 11 age- and gender-matched normal subjects. In addition, we investigated whether, in patients with ET, an inhibitory repetitive transcranial magnetic stimulation (1 Hz-rTMS) over lateral cerebellum was able to change timing properties and motor behaviour. Patients with ET showed a longer touch duration (TD) and a lower inter tapping interval (ITI) than normal subjects. The temporal variability of the movement (coefficient of variation of ITI) was increased in patients with ET. Neither clinical rating scale or tremor measurements correlated with any parameter of motor performance in the ET group. 1 Hz-rTMS over ipsilateral lateral cerebellum transiently affected the performance of patients with ET, by reducing TD values and normalizing ITI values. After 1 Hz-rTMS, the coefficient of variation of ITI was restored to values similar to those of normal subjects. We postulate that the strategy to increase TD, probably adopted to allow a better perception of movement, can affect ITI and its variability. The results support the idea that the cerebellum plays a central role in the selection of motor strategy of rhythmic finger movements, particularly in terms of temporal organization of movement.


"Death Knell" for Prophylactic Vena Cava Filters? A 20-Year Experience with a Venous Thromboembolism Guideline.
The role of prophylactic vena cava filters (pVCFs) in trauma patients remains controversial. After 20 years of data collection and experience, we reviewed our venous thromboembolism guideline for the efficacy of pVCFs in preventing pulmonary embolism (PE). A retrospective cohort study was performed using our Level I trauma center registry from January 1997 thru December 2016. This population was then divided by the presence of pVCFs. Univariate analysis was performed comparing the incidence of PEs, deep vein thrombosis, and mortality between those with and without a pVCF. There were 35,658 patients identified, of whom 2 per cent (n = 847) received pVCFs. The PE rate was 0.4 per cent in both groups. The deep vein thrombosis rate for pVCFs was 3.9 per cent compared with 0.6 per cent in the no-VCF group (P < 0.0001). Given that there was no difference in the rates of PEs between the cohorts, the subset of patients with a PE were analyzed by their risk factors. Only ventilator days > 3 were associated with a higher risk in the no-pVCF group (0.2 vs 1.5%, P = 0.033). pVCFs did not confer benefit reducing PE rate. In addition, despite their intended purpose, pVCFs cannot eliminate PEs in high-risk trauma patients, suggesting a lack of utility for prophylaxis in this population.


[Infratentorial oligodendroglioma: report of a case].
Oligodendroglioma occurs primarily in the cerebral hemisphere in adult. A rare case of oligodendroglioma in the cerebellum is presented, and previous reported cases were reviewed. A thirty-one year old female was admitted to our service only with headache. CT scan demonstrated a low density mass in the vermis of the cerebellum which was not enhanced. Bilateral vertebral angiography showed an avascular mass in the vermis. The preoperative diagnosis was astrocytoma or ependymoma, and a suboccipital craniotomy was performed. The tumor which was soft, yellowish gray and well-circumscribed, was developed from the vermis and extended into the cisterna magna. The tumor which size was approximately 3 X 4 X 5 cm. Microscopically the specimen showed round, darkly stained nuclei and clear perinuclear cytoplasmic halos. Moreover, the immunoperoxidase method testified the absence of glial fibrillary acidic protein in the tumor cells. The pathological diagnosis was oligodendroglioma. Post-operatively the patient was doing well without any complications. There was no clinical nor CT evidence of tumor recurrence forty months after resection. The 11 reported cases of infratentorial oligodendroglioma including ours were analyzed and the following conclusion was obtained. Infratentorial oligodendroglioma occurs in the younger age group. The tumor has special tendency to form cyst. Frequency of calcification is low. Prognosis is good if the tumor is resected in early stage. Pre-operatively, however, it was difficult to differentiate oligodendroglioma from astrocytoma.


Inflammatory cytokines induce neutrophil extracellular traps interaction with activated platelets and endothelial cells exacerbate coagulation in moderate and severe essential hypertension.
Essential hypertension (EH) patients suffer from paradoxically thrombotic rather than haemorrhagic, although the exact mechanism remains elusive. Our aim is to explore whether and how neutrophil extracellular traps (NETs) play the procoagulant role in EH patients, as well as evaluated whether the NET releasing were triggered by inflammatory cytokines. The concentration of plasma NETs components were detected by ELISA. The morphology of cells and NETs formation were analysed using immunofluorescence. Procoagulant activity was analysed by clotting time, purified coagulation complex and fibrin generation assays. Phosphatidylserine (PS) exposure on endothelial cells (ECs) was analysed with flow cytometry. Moderate to severe EH patients plasma NETs levels were significantly higher compared to mild EH patients or controls. Furthermore, inflammatory cytokines can induce NETs generation, depleting these patients plasma inflammatory cytokines led to a reduction in NET releasing. NETs from moderate to severe EH patients neutrophils led to significantly decreased clotting time (CT), increased potency to generate thrombin and fibrin (all P < 0.05). These procoagulant effects were markedly attenuated by approximately 70% using DNase I. Additionally, high concentrations NETs exerted a strong cytotoxic effect on ECs, conferring them a procoagulant phenotype. Our study reveals that EH drives a systemic inflammatory environment, which, in turn, drives neutrophils to prime and NET releasing, and found a link between hypercoagulability and NETs levels in moderate to severe EH patients. Therefore, anti-inflammatory combined with block the generation of NETs may represent a new therapeutic target for preventing thrombosis in EH patients.


Disseminated Cutaneous and Osteoarticular Sporotrichosis Mimicking Pyoderma Gangrenosum.
Disseminated sporotrichosis may present with inflammatory arthritis and cutaneous ulcerations that mimic noninfectious skin conditions such as pyoderma gangreonsum (PG). Sporotrichosis must therefore be ruled out before administering immunosuppressive agents for PG. Furthermore, dimorphic fungi such as sporotrichosis may grow as yeast in bacterial cultures, even before fungal cultures become positive. We present a case of disseminated cutaneous and osteoarticular sporotrichosis mimicking PG and describe the differential diagnosis and the diagnostic and treatment approach to this condition.


A Two-Step Microwave Annealing Process for PAN Pre-Oxidation through a TM-Mode Cavity.
A novel microwave annealing system and a specific processing condition are proposed for the pre-oxidation of carbon fiber. The microwave annealing system consists of a TM-mode resonant cavity and a silicon carbide (SiC) susceptor. The TM-mode cavity enhances the electric field at the center. The SiC susceptor absorbs part of the microwave energy and converts it to heat. The enhanced fields and the SiC susceptor provide both nonthermal and thermal treatments for fibrous materials with various dielectric properties. Furthermore, a two-step microwave annealing process is used to oxidize polyacrylonitrile (PAN) fiber. The scanning electron microscopy (SEM) images, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) results support the theory that the microwave annealing can achieve a high aromatic index of 66.39% in just 13 min, 9 times faster than the traditional processing time. The results of the Raman spectra also illustrate that the sheath-core factor of the microwave-heated specimen is closer to one than that of the conventional furnace-heated type, which agree with the images of the cross-section area.


Oxidative Modification in the Salivary Glands of High Fat-Diet Induced Insulin Resistant Rats.
Still little is known about the role of oxidative stress (OS) in the pathogenesis of the salivary gland dysfunction in the course of insulin resistance (IR). To induce IR rats was fed with a high fat diet (HFD) during 8 weeks. Stimulated and non-stimulated salivary flow rate, total protein, as well as oxidative damage markers: 4-HNE protein adduct, 8-isoprostanes (8-isoP), 8-hydroxy-D-guanosine (8-OHdG), advanced oxidation protein product (AOPP), and protein carbonyls (PC) were determined in the plasma and submandibular and parotid glands of IR and control rats. We have shown a significant decrease (45%) of the stimulated salivary flow rate, and in the total protein concentration in the parotid (35%) and submandibular (10%) glands of HFD IR as compared to the control rats. The level of 4-HNE protein adduct (15%) and 8-isoP (20%) in the submandibular glands of IR rats as well as total level of 4-HNE protein adduct (39%), 8-isoP (27%), AOPP (25%), PC (32%), and 8-OHdG (18%) in the parotid glands of IR rats were significantly higher as compared to the control group. We showed no correlation between the assessed OS parameters in the plasma and salivary glands. However, the redox balance in both glands shifted toward the oxidative status, parotid glands of IR rats are exposed to greater intensity OS. Stimulated secretory ability and mechanisms involved in the synthesis/secretion of proteins in the salivary glands are depressed in the course of IR. Oxidative damage in the salivary glands arises independently from the general OS in the course of insulin resistance induced by a high fat diet.


Effects of growth in low potassium medium or ouabain on membrane Na,K-ATPase, cation transport, and contractility in cultured chick heart cells.
Growth of cultured cells in low potassium medium has been shown to result in an increase in the number of Na,K-ATPase sites. This phenomenon and its physiological and pharmacological consequences were examined in spontaneously beating monolayers of cultured chick heart cells. Growth of cells in 1 mM extracellular potassium, 2 microM ouabain, or 1 microM veratridine for 48 hours caused 60%, 40%, or 20% increases, respectively, in the total number of specific ouabain binding sites measurable in intact cells. Acute exposure of control cells grown in 4 mM to 1 mM extracellular potassium caused elevation of steady state [Na+]i by 37%, while 1 microM veratridine exposure increased [Na+]i by 12%. After 48 hours of growth in 1 mM extracellular potassium, intracellular sodium concentrations declined to near-control levels. In cells grown in low extracellular potassium and then equilibrated with 4 mM potassium for 30 minutes, the positive inotropic effects of 1 mM extracellular potassium and 0.3 microM isoproterenol, expressed as a percent of contractile response to 3.6 mM calcium, were 40 +/- 6% and 37 +/- 5% (means +/- SEM), respectively, in low potassium-grown cells, compared with 63 +/- 8% and 35 +/- 4% in control cells. Growth of cells in low potassium shifted the concentration-effect curve for ouabain to the right. The rapid component of calcium uptake in zero extracellular sodium was significantly lower in low potassium-grown cells than in control cells after equilibration in 1 mM extracellular potassium for 30 minutes. These findings demonstrate that prolonged exposure of cultured heart cells to 1 mM extracellular potassium or ouabain causes induction of additional functional sarcolemmal sodium pump sites. The increased levels of intracellular sodium caused by these interventions appear to be an important determinant of sodium pump site density. The reduced contractile response of cells grown in 1 mM extracellular potassium and ouabain (but not isoproterenol) supports the view that elevated intracellular sodium due to Na,K-ATPase inhibition mediates the positive inotropic response to low extracellular potassium and ouabain, probably via augmented transsarcolemmal sodium-calcium exchange. In addition, our results support a mechanism of inotropic action of digitalis glycosides based on inhibition of the sodium pump rather than altered calcium binding properties of sarcolemmal sites due to cardiac glycoside binding to Na,K-ATPase.


Observation of the effects of dust particles on plasma fluctuation spectra.
Charged dust particles are theoretically expected to modify the amplitude and spectrum of plasma fluctuations, and this can eventually provide novel diagnostic tools. Direct experimental evidence of the effects of dust particles on the fluctuations of a low collisionality plasma is reported, in agreement with the expectations of kinetic theory.


Risk of Cardiovascular Diseases and Cancer in Later Life: The Role of Age at First Marriage.
The objective of this study was to examine how age at first marriage is related to the risk of developing cardiovascular diseases and cancer in later life. We analyzed longitudinal data from a nationally representative sample of 2129 older adults (born in the 1940s or earlier) in the National Social Life, Health, and Aging Project. We found that for men in this cohort, the age at first marriage that was related to the lowest risk of cardiovascular diseases (CVD) and cancer in later life was the early 30s; men who first married at either younger or older ages had significantly higher odds of experiencing CVD and cancer. Interestingly, for women in this cohort, the age at first marriage was not related to the risk of either CVD or cancer.


Silencing of the p18INK4c gene by promoter hypermethylation in Reed-Sternberg cells in Hodgkin lymphomas.
p18INK4c is a cyclin-dependent kinase (CDK) inhibitor that interferes with the Rb-kinase activity of CDK6/CDK4. Disruption of p18INK4c in mice impairs B-cell terminal differentiation and confers increased susceptibility to tumor development; however, alterations of p18INK4c in human tumors have rarely been described. We used a tissue-microarray approach to analyze p18INK4c expression in 316 Hodgkin lymphomas (HLs). Nearly half of the HL cases showed absence of p18INK4c protein expression by Reed-Sternberg (RS) cells, in contrast with the regular expression of p18INK4c in normal germinal center cells. To investigate the cause of p18INK4c repression in RS cells, the methylation status of the p18INK4c promoter was analyzed by methylation-specific polymerase chain reaction (PCR) and bisulfite sequencing. Hypermethylation of the p18INK4c promoter was detected in 2 of 4 HL-derived cell lines, but in none of 7 non-Hodgkin lymphoma (NHL)-derived cell lines. We also detected p18INK4c hypermethylation, associated with absence of protein expression, in 5 of 26 HL tumors. The correlation of p18INK4c immunostaining with the follow-up of the patients showed shorter overall survival in negative cases, independent of the International Prognostic Score. These findings suggest that p18INK4c may function as a tumor suppressor gene in HL, and its inactivation may contribute to the cell cycle deregulation and defective terminal differentiation characteristic of the RS cells.


Direct presynaptic regulation of GABA/glycine release by kainate receptors in the dorsal horn: an ionotropic mechanism.
In the spinal cord dorsal horn, excitatory sensory fibers terminate adjacent to interneuron terminals. Here, we show that kainate (KA) receptor activation triggered action potential-independent release of GABA and glycine from dorsal horn interneurons. This release was transient, because KA receptors desensitized, and it required Na+ entry and Ca2+ channel activation. KA modulated evoked inhibitory transmission in a dose-dependent, biphasic manner, with suppression being more prominent. In recordings from isolated neuron pairs, this suppression required GABA(B) receptor activation, suggesting that KA-triggered GABA release activated presynaptic GABA(B) autoreceptors. Finally, glutamate released from sensory fibers caused a KA and GABA(B) receptor-dependent suppression of inhibitory transmission in spinal slices. Thus, we show how presynaptic KA receptors are linked to changes in GABA/glycine release and highlight a novel role for these receptors in regulating sensory transmission.


[Biocompatibility of implants with and without fluorohydrocarbon glow-discharge polymer coating. 3. Mathematical models of the subsiding processes of the tissue reaction].
The subsidence process of the tissue reaction was estimated by the thickness of the fibrous capsule as well as different histologic characteristics in dependence on the period after the implantation of 4 several implant materials. This subsidence process was fitted mathematically by an exponential function respectively a power function by means of the regression analysis. The power function described best the experimentally found curve. The correspondence, on principle, of the subsidence process of the fibrous capsula thickness on the one hand and the 9 histologic characteristics on the other hand could be proved. A standard valuation for subcutaneous tests is demanded which include the designation of the thickness of the fibrous capsula as well as characteristic cell type frequencies as histologic characteristics.


[Special surgical complications in chronic inflammatory bowel diseases].
After colorectal and anorectal interventions for chronic inflammatory bowel diseases, specific complications can occur.In Crohn's disease these complications mainly occur after proctocolectomy. Pelvic sepsis can be prevented by omentoplasty with fixation inside the pelvis. A persisting sepsis of the sacral cavity can be treated primarily by dissection of the anal sphincter which ensures better drainage. In cases of chronic sacral sepsis, transposition of the gracilis muscle is a further effective option. Early recurrence of a transsphincteric anal fistula should be treated by reinsertion of a silicon seton drainage.Complications after restorative proctocolectomy are frequent and manifold (35%). The main acute complications are anastomotic leakage and pelvic sepsis. Therapy consists of transperineal drainage of the abscess with simultaneous transanal drainage. Late complications due to technical and septic reasons are still a relevant problem even 36 years after introduction of this operative technique. A consistent approach with detailed diagnostic and surgical therapy results in a 75% rescue rate of ileoanal pouches.


Case Report: Novel Pathogenic Variant Detected in Two Siblings with Type 1 Gaucher Disease.
Gaucher disease (GD) is an autosomal recessive lysosomal storage disease. The disease develops due to glucocerebrosidase enzyme deficiency caused by biallelic pathogenic variants in the glucosylceramidase beta 1 (GBA1) gene, which encodes the glucocerebrosidase enzyme. The GBA1 gene is located at chromosomal location 1q22 and consists of 11 exons. In this article, we report a novel pathogenic variant in the GBA1 gene. A 32-year-old female patient with no known chronic disease was admitted with complaints of weakness, bone pain, and abdominal pain. Her evaluation included hepatosplenomegaly, thrombocytopenia, osteoporosis, and anemia. The clinical suspicion of Gaucher disease was confirmed by glucocerebrosidase enzyme level and genetic testing. In her family screening, her sister also had hepato-splenomegaly, osteoporosis, thrombocytopenia, and anemia. Both sisters had no neurological symptoms. As a result of GBA1 gene sequence analysis in two of our patients, a missense variant was detected in the c.593C>A homozygous genotype. This variant has not been reported in any previously published case. In this case report, we aimed to contribute to the literature by reporting a new novel pathogenic variant in the GBA1 gene leading to type 1 Gaucher disease that has not been described before.


[Malnutrition common in Swedish hospitals. Risk of complications and prolonged care increases].
The occurrence of malnutrition has been investigated at four hospitals and the underlaying factors evaluated. The results suggest that malnutrition is still a manifest clinical problem at Swedish hospitals, and that it is associated with an increased risk of complications and prolonged care. During hospitalisation a negative nitrogen and energy balance is observed. It is important to identify patients at risk, as the prevention of undernourishment would appear to be a more effective approach than the treatment of established malnutrition.


Endogenous interleukin-1 can regulate the autonomous growth of the blast cells of acute myeloblastic leukemia by inducing autocrine secretion of GM-CSF.
We have studied peripheral blood blast cells from a patient with acute myeloblastic leukemia (AML) whose cells proliferated autonomously at high cell density, but only in the presence of adherent cells. At low cell density in suspension culture and in a clonogenic assay, blast cell growth was stimulated by recombinant granulocyte macrophage colony stimulating factor (GM-CSF) and recombinant interleukin-1 (IL-1) independently. The response to rIL-1 was inhibited (less than 90%) by anti-GM-CSF, suggesting that the proliferative response to IL-1 was mediated by GM-CSF. This was supported by experiments which demonstrated that blast cell conditioned medium prepared in the presence of IL-1 contained GM-CSF activity which stimulated the growth of normal granulocyte-macrophage precursors (CFU-GM) and of homologous GM-CSF responsive AML blasts. As IL-1 but no GM-CSF activity was detected in BCCM prepared without exogenous IL-1 and a neutralizing antibody to IL-1 inhibited the autonomous growth of blasts in suspension culture, we conclude that the endogenous secretion of IL-1 by leukemic cells stimulated autocrine GM-CSF secretion, inducing autonomous growth of the blast cell population.


[Observation on polytene chromosomes of the ovarian nurse cell of anopheles minimus from Yuanjiang].
Anopheles minimus collected from Yuanjiang, Yunnan Province, were bred with standard methods in lab. The ovarian nurse cells of A.minimus were separated and stained, and the whole polytene chromosomes were photographed under light microscope and compared with A.minimus from Guangxi. 365 samples of ovarian nurse cells were observed. The chromosomes included one telocentric sex-chromosome X, two submetacentric autosomes II (autosome II right arm, 2R and autosome II left arm, 2L) and two metacentric autosomes III (autosome III right arm, 3R, and autosome III left arm, 3L). The X is the shortest chromosome and the 2R is the longest one. In comparison with the pattern of polytene chromosomes of A. minimus from Guangxi, difference at 12 positions has been found at the parts of arms in banding sequences.


An experimental study on silver in the nervous system and on aspects of its general cellular toxicity.
Exposure of foetal and adult rats to silver results in a long-lasting deposition of the metal in many structures of the nervous system. A brief anatomical description of the localization of silver deposits as they are visualized by autometallography is provided. The consequences of silver in the nervous system were evaluated by volumetric measurements on developing rat hippocampi which showed that silver induced a decrease in the total volume of hippocampal pyramidal cells. The toxicity of silver at the cellular level was studied in a test-system of cultured macrophages. High doses of silver caused coagulation necrosis, whereas lower concentrations resulted in a cytotoxic and possibly a cytostatic effect without affecting cell structure. The processing of silver which resulted in lysosomal accumulations was affected by the metal itself in a dose-dependent fashion (autointerference). Other basic macrophage functions (protein-production, phagocytosis, migration) were not affected by silver at concentrations which did not cause acute cell death. Biochemically, silver causes an increase in lipid peroxidation, which was evident only in liver tissue. Coagulation necrosis and, to some extent, long-term effects on cell viability could be reversed by inorganic selenium, which was tested as a detoxicant. On the other hand, pre-exposure of animals to selenium greatly enhanced the silver-induced lipid peroxidation. Furthermore, the co-exposure to silver and nickel resulted in a synergistically increased lipid peroxidation.


Thoracic epidural anesthesia improves the gastric microcirculation during experimental gastric tube formation.
Gastric tube formation is a surgical technique to reestablish the continuity of the gastrointestinal tract after esophagectomy. Our aims were to study the microcirculatory consequences of experimental gastric tube formation and characterize the effects of thoracic epidural anesthesia (TEA) during this condition. The experiments were performed on mongrel dogs anesthetized with pentobarbital. The stomach was prepared for replacement according to the method of Akiyama, and TEA was induced with bupivacaine (1 mg/kg). Macrohemodynamics, intramucosal pH, and gastric motility changes were monitored, and intravital video-microscopy with orthogonal polarization spectral imaging technique was used to observe the gastric microcirculation. The gastric pull-up induced a significant decrease in intramucosal pH. The functional capillary density of the mucosa or subserosa did not change; the red blood cell velocity in the capillaries of the upper part of the gastric tube was decreased in the mucosa, as well as on the serosal side. After epidural anesthesia the red blood cell velocity returned to the baseline, and the gastric and intestinal motility index was significantly increased. TEA significantly improves the microcirculation of the distal portion of the gastric tube and increases the intestinal and gastric motility after gastric pull-up. The procedure is favorable and should be recommended during reconstructive esophageal surgery.


Patterns of flexibility, laxity, and strength in normal shoulders and shoulders with instability and impingement.
Imbalance of the internal and external rotator musculature of the shoulder, excess capsular laxity, and loss of capsular flexibility, have all been implicated as etiologic factors in glenohumeral instability and impingement syndrome; however, these assertions are based largely on qualitative clinical observations. In order to quantitatively define the requirements of adequate protective synergy of the internal and external rotator musculature, as well as the primary capsulolabral restraints, we prospectively evaluated 53 subjects: 15 asymptomatic volunteers, 28 patients with glenohumeral instability, and 10 patients with impingement syndrome. Range of motion was evaluated by goniometric technique in all patients with glenohumeral instability and impingement. Laxity assessment was performed and anterior, posterior, and inferior humeral head translation was graded on a scale of 0 to 3+. Isokinetic strength assessment was performed in a modified abducted position using the Biodex Clinical Data Station with test speeds of 90 and 180 deg/sec. Internal and external rotator ratios and internal and external rotator strength deficits were calculated for both peak torque and total work. Patients with impingement demonstrated marked limitation of shoulder motion and minimal laxity on drawer testing. Both anterior and multidirectional instability patients had excessive external rotation as well as increased capsular laxity in all directions. Sixty-eight percent of the patients with instability had significant impingement signs in addition to apprehension and capsular laxity. Isokinetic testing of asymptomatic subjects demonstrated a 30% greater internal rotator strength in the dominant shoulder. Comparison of all three experimental groups demonstrated a significant difference between internal and external rotator ratios for both peak torque and total work. Conclusions are that there appears to be a dominance tendency with regard to internal rotator strength in asymptomatic individuals. Impingement syndrome and anterior instability have significant differences in both strength patterns of the rotator muscles and flexibility and laxity of the shoulder. Isokinetic testing potentially may be helpful in diagnostically differentiating between these two groups in cases where there is clinical overlap of signs and symptoms.


Cell numbers and leaf development in Arabidopsis: a functional analysis of the STRUWWELPETER gene.
The struwwelpeter (swp) mutant in Arabidopsis shows reduced cell numbers in all aerial organs. In certain cases, this defect is partially compensated by an increase in final cell size. Although the mutation does not affect cell cycle duration in the young primordia, it does influence the window of cell proliferation, as cell number is reduced during the very early stages of primordium initiation and a precocious arrest of cell proliferation occurs. In addition, the mutation also perturbs the shoot apical meristem (SAM), which becomes gradually disorganized. SWP encodes a protein with similarities to subunits of the Mediator complex, required for RNA polymerase II recruitment at target promoters in response to specific activators. To gain further insight into its function, we overexpressed the gene under the control of a constitutive promoter. This interfered again with the moment of cell cycle arrest in the young leaf. Our results suggest that the levels of SWP, besides their role in pattern formation at the meristem, play an important role in defining the duration of cell proliferation.


Circulating Biomarkers of Colorectal Cancer (CRC)-Their Utility in Diagnosis and Prognosis.
The global burden of colorectal cancer (CRC) is expected to increase, with 2.2 million new cases and 1.1 million annual deaths by 2030. Therefore, the establishment of novel biomarkers useful in the early diagnosis of CRC is of utmost importance. A number of publications have documented the significance of the overexpression of several specific proteins, such as inflammatory mediators, in CRC progression. However, little is known about the potential utility of these proteins as circulating blood tumor biomarkers of CRC. Therefore, in the present review we report the results of our previous original studies as well as the findings of other authors who investigated whether inflammatory mediators might be used as novel biomarkers in the diagnosis and prognosis of CRC. Our study revealed that among all of the tested proteins, serum M-CSF, CXCL-8, IL-6 and TIMP-1 have the greatest value in the diagnosis and progression of CRC. Serum TIMP-1 is useful in differentiating between CRC and colorectal adenomas, whereas M-CSF and CRP are independent prognostic factors for the survival of patients with CRC. This review confirms the promising significance of these proteins as circulating biomarkers for CRC. However, due to their non-specific nature, further validation of their sensitivity and specificity is required.


Incidence of Cellulitis in Lower Extremity Burns: 6-Year Analysis.
Patients with burn wounds of the lower extremities are at increased risk of developing cellulitis. The probability of developing burn-associated cellulitis is presumed to be correlated with a medical history of diabetes, the etiology of the burn, delay in hospitalization of the patient during their initial presentation, and depth of the burn itself. This study aims to identify factors that place patients at increased risk for developing lower extremity burn wound cellulitis. A retrospective chart review was performed of all Nassau University Medical Center Burn Center admissions from January 2010 to January 2016. All patients admitted with burns of any etiology isolated to the lower extremity were included in this study. Patients who were evaluated and followed as an outpatient were not included in this study. Pediatric patients less than or equal to 12 years of age were excluded from this study. Of the 218 admissions for lower extremity burns during the 6-year study period, 34% of patients developed cellulitis. Risk factors for developing lower extremity burn wound cellulitis included being male, greater depth of burn, and burn-to-admission delay. This was true in both univariate and multivariate analysis. total body surface area was a risk factor on univariate analysis but was not found to be an independent risk factor on multivariate analysis. No difference was observed in the development of cellulitis in patients discharged on oral antibiotics compared with those not given antibiotics. Burn wound cellulitis is the second most common complication observed in burns. Identification of patients at risk for developing cellulitis is important. Admitting these patients at increased risk and excising and grafting the burned area is a reasonable solution in preventing this costly complication.


The HEART Pathway Randomized Controlled Trial One-year Outcomes.
The objective was to determine the impact of the HEART Pathway on health care utilization and safety outcomes at 1 year in patients with acute chest pain. Adult emergency department (ED) patients with chest pain (N = 282) were randomized to the HEART Pathway or usual care. In the HEART Pathway arm, ED providers used the HEART score and troponin measures (0 and 3 hours) to risk stratify patients. Usual care was based on American College of Cardiology/American Heart Association guidelines. Major adverse cardiac events (MACE-cardiac death, myocardial infarction [MI], or coronary revascularization), objective testing (stress testing or coronary angiography), and cardiac hospitalizations and ED visits were assessed at 1 year. Randomization arm outcomes were compared using Fisher's exact tests. A total of 282 patients were enrolled, with 141 randomized to each arm. MACE at 1 year occurred in 10.6% (30/282): 9.9% in the HEART Pathway arm (14/141; 10 MIs, four revascularizations without MI) versus 11.3% in usual care (16/141; one cardiac death, 13 MIs, two revascularizations without MI; p = 0.85). Among low-risk HEART Pathway patients, 0% (0/66) had MACE, with a negative predictive value (NPV) of 100% (95% confidence interval = 93%-100%). Objective testing through 1 year occurred in 63.1% (89/141) of HEART Pathway patients compared to 71.6% (101/141) in usual care (p = 0.16). Nonindex cardiac-related hospitalizations and ED visits occurred in 14.9% (21/141) and 21.3% (30/141) of patients in the HEART Pathway versus 10.6% (15/141) and 16.3% (23/141) in usual care (p = 0.37, p = 0.36). The HEART Pathway had a 100% NPV for 1-year safety outcomes (MACE) without increasing downstream hospitalizations or ED visits. Reduction in 1-year objective testing was not significant.


Racial differences in two measures of trust in biomedical research.
Lack of trust toward medical research is a major barrier to research participation, particularly among some population groups. Valid measures of trust are needed to develop appropriate interventions. The study purpose was to compare two previously validated scales that measure trust in biomedical research - one developed by Hall et al. (H-TBR; 2006) and the other by Mainous et al. (M-TBR; 2006) - in relation to socio-demographic variables and attitudes toward research. Differences between Black and White respondents were explored. Two nearly identical surveys - one with H-TBR and the other with M-TBR - were systematically administered to a convenience sample. Internal consistency reliability of each scale was assessed. Associations were computed between scores on each scale with attitudes toward biomedical research and demographic variables (i.e., gender, age, race, and socioeconomic status). The difference between White and Black respondents on each TBR score while controlling for age, education, and race was also investigated. A total of 2020 participants completed the H-TBR survey; 1957 completed the M-TBR survey. Mean item scores for M-TBR were higher (F = 56.05, p < 0.001) among Whites than Blacks. Whites also had higher mean item scores than Blacks on H-TBR (F = 7.09, p < 0.001). Both scales showed a strong association with participants' perceived barriers to research (ps < 0.001) and significant, positive correlations with interest in research participation (ps < 0.001). Age and household income were positive predictors of TBR scores, but the effects of education differed. Both scales are internally consistent and show associations with attitudes toward research. Whites score higher than Blacks on both TBR scales, even while controlling for age and socioeconomic status.


[Study on the haemostatic efficiency of composite bio-particles].
A porous composite particle (CP) was fabricated by the methods of emulsification and cross-link based on chitosan, alginate and collagen protein, and the tranexamic acid-loaded composite particles (TACP) was prepared by immersing the composite particle into the solution of tranexamic acid and by freeze drying. In the hepatic and splenic hemorrhage model of rabbits, CP and TACP were randomly used as haemostatic agents, and the Suxiaozhixuefen (Flashclot) was used as control. The corresponding hemostatic time and bleeding amount were observed respectively. The hemostatic time of CP and Flashclot were (2.48 +/- 0.88) min and (3.07 +/- 0.84) min, respectively, no significant difference was observed. However, the hemostatic time of TACP was (1.90 +/- 0.75) min, which was significantly shorter than that of CP and Flashclot (P < 0.05). In the splenic bleeding model of rabbits, similar results were obtained with these three kinds of hemostatics. These results indicated that the CP based on chitosan, alginate and collagen protein displayed similar hemostatic efficiency to Flashclot. However, the TACP might be one of promising haemostatic powders due to its more excellent hemostatic efficiency.


Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases.
HIV-2 protease (PR2) is naturally resistant to most FDA (Food and Drug Administration)-approved HIV-1 protease inhibitors (PIs), a major antiretroviral class. In this study, we compared the PR1 and PR2 binding pockets extracted from structures complexed with 12 ligands. The comparison of PR1 and PR2 pocket properties showed that bound PR2 pockets were more hydrophobic with more oxygen atoms and fewer nitrogen atoms than PR1 pockets. The structural comparison of PR1 and PR2 pockets highlighted structural changes induced by their sequence variations and that were consistent with these property changes. Specifically, substitutions at residues 31, 46, and 82 induced structural changes in their main-chain atoms that could affect PI binding in PR2. In addition, the modelling of PR1 mutant structures containing V32I and L76M substitutions revealed a cooperative mechanism leading to structural deformation of flap-residue 45 that could modify PR2 flexibility. Our results suggest that substitutions in the PR1 and PR2 pockets can modify PI binding and flap flexibility, which could underlie PR2 resistance against PIs. These results provide new insights concerning the structural changes induced by PR1 and PR2 pocket variation changes, improving the understanding of the atomic mechanism of PR2 resistance to PIs.


[A case of retroperitoneal neuroblastoma in an adult with extensive bone marrow metastasis].
We present a case of retroperitoneal neuroblastoma in a 27-year-old male with extensive bone marrow metastasis at the first presentation. After the simple excision of the tumor, adjuvant multi-drug chemotherapy, consisting of vincristine, actinomycin-D, ifosfamide, doxorubicin, carboplatin and etoposide, was carried out for 17 months, leading to complete remission. Ten months after completion of the chemotherapy, the tumor recurred with bone marrow metastasis. He further developed thoracic vertebral metastases resulting in paraplegia, and died of the disease 41 months after the presentation. The clinical course of this case, with its emphases especially on the effect of the chemotherapy, is described in this report. Since the clinical characteristics and treatment strategies for adult neuroblastoma have not yet been well established, they remain to be investigated in detail.


Phytochemical constituents and antibacterial efficacy of the flowers of Peltophorum pterocarpum (DC.) Baker ex Heyne.
To investigate the preliminary phytochemistry and antibacterial activity of the flower extract of Peltophorum pterocarpum . Phytochemical analysis was done by using the standard methods given by Harbone. The methanolic flower extract were tested against Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus, Salmonella typhi, Serratia marsecens, Acinetobacter baumannii, Enterobacter sp., Proteus mirabilis, Enterococcus faecalis and Streptococcus pyogenes by the agar disc diffusion method. Preliminary phytochemical screening of flower extract showed the presence of phenolic compounds, flavonoids, saponins, steroids, tannins, xanthoproteins, carboxylic acids, coumarins and carbohydrates. The flower extract of Peltophorum pterocarpum showed significant activity against four gram positive (Staphylococcus aureus, Bacillus cereus, Enterococcus faecalis and Streptococcus pyogenes) and three gram negative bacteria (Proteus mirabilis, Acinetobacter baumannii and Serratia marsecens), out of 12 pathogenic bacteria studied. The findings of the present study confirm the presence of significant antibacterial activity against human pathogens in the flowers of Peltophorum pterocarpum.


GROWTH-INHIBITORY EFFECTS OF FARNESOL AGAINST SCEDOSPORIUM BOYDII AND LOMENTOSPORA PROLIFICANS.
Scedosporium boydii and Lomentospora prolificans are filamentous fungi reported to cause infection in immunocompromized individuals. We studied the effect of farnesol to inhibit growth of S. boydii and L. prolificans by measuring colony diameter and determining minimal effective concentration (MEC). S. boydii and L. prolificans were grown on Sabouraud dextrose agar (SDA) at 37oC for 5 days. Conidia were collected and adjusted to a concentration of 104 conidia/ ml. Twenty microliters of conidia suspension was placed in each well of a sixwell plate containing serial dilutions of farnesol (10 μM, 100 μM, 1,000 μM, and 10,000 μM) in SDA. Colony morphology and diameter were observed on days 1, 2, 3, and 4. Farnesol at concentrations of 1,000 μM or higher caused the colony diameter of both S. boydii and L. prolificans to be smaller than untreated controls in a dose-dependent manner. The MEC of farnesol to inhibit growth of both S. boydii and L. prolificans was 3.2 mM. This study reveals the antifungal property of farnesol against S. boydii and L. prolificans, which can be used for further study as an alternative antifungal agent against these fungal infections.


Wire-assisted minor papilla precut papillotomy.
Deep cannulation of the dorsal duct in patients with pancreas divisum may not be possible, even for the experienced endoscopist. This is a description of a technique to facilitate access to the dorsal duct. Patients undergoing dorsal ductography in whom endoscopic therapy was indicated and in whom a 4.5F tapered-tip catheter could not be passed into the dorsal duct over a guidewire were prospectively identified. After ductal opacification, either a 0.035- or 0.021-inch guidewire was passed into the dorsal duct; a needle-knife was then passed to the minor papilla alongside the guidewire, and with appropriate orientation, a precut papillotomy was made. Eleven patients undergoing dorsal ductography for recurrent pancreatitis (10 patients) or ductal leak (1 patient) were prospectively treated with the above technique. Secretin was used in 1 patient. In all patients, after precut papillotomy the diagnostic catheter was passed without difficulty into the dorsal duct allowing for guidewire exchange and/or stent placement. Extension of the papillotomy could then be performed with the needle-knife over a pancreatic stent. Complications included pancreatitis in 1 patient. This technique, which uses widely available accessories, facilitates access to the dorsal pancreatic duct for endoscopic therapy.


[Tobacco smoking--anthropological context of human dependence].
In the papers concerning the subject of prevention and treatment of addiction to tobacco smoking, the philosophical data on nature of man, his reason and freedom are unfairly disregarded. The anthropological description of the features constituting the human nature refers, above all, to reason, will, freedom, and to a lesser extent, instinct and imagination. In the analyses of addiction to tobacco smoking, the rational cognition and free will are of greatest significance. Values as well as freedom and good also play a role in counteracting the enslavement of man. The investigations of the essence of man indicate that even the deepest addiction does not change and does not destroy the reason and free will which are characteristic of a human being. It means that a person addicted to a habit always requires respect, compassion and hope in overcoming the enslavement. It touches the whole human being and should be treated integrally. Addiction is inherent to a man and not the human nature, tobacco smoking will always be contrary to reason and freedom of a human being and the whole mankind.


Medicinal cupping therapy in 30 patients with fibromyalgia: a case series observation.
The aim of this study was to evaluate the therapeutic effect of traditional medicinal cupping for treatment of fibromyalgia. A prospective case series was conducted in 30 consecutive patients with fibromyalgia at an outpatient department in a hospital in Beijing. Patients were diagnosed according to the criteria set by the American College of Rheumatology (1990). A bamboo cup, boiled in herbal decoction for 5 min, was applied to Ashi points for 10 min once daily for 15 days. Pain, assessed via a 10-point visual analogue scale (VAS), and the number of tender points were recorded at baseline, 5, 10, 15 days, and 2 weeks following the final treatment. At baseline, the average pain was 2.63 ± 0.73 on the VAS, and patients had an average of 13.5 ± 1.66 tender points. The pain scores decreased from baseline during treatment (2.22 ± 0.77 at 5 days, 1.78 ± 0.75 at 10 days, and 1.36 ± 0.76 at 15 days) as did the number of tender points (12.57 ± 2.25 at 5 days, 11.2 ± 2.50 at 10 days, 9.33 ± 2.89 at 15 days). A total of 29 patients completed follow-up 2 weeks after the final treatment, which suggested the reduction in pain and tender points was sustained (1.31 ± 0.76 for VAS; 9.07 ± 2.96 for pain points). There were no serious adverse effects as a result of cupping. Medicinal cupping therapy was associated with a reduction in fibromyalgia symptoms for both pain ratings and number of tender points. The findings from this case series should be tested in a controlled clinical trial.


Theoretical investigation of linalool oxidation.
This study concerns the autoxidation of one of the most used fragrances in daily life, linalool (3,7-dimethyl-1,6-octadien-3-ol). It reacts with O2 to form hydroperoxides, which are known to be important contact allergens. Pathways for hydroperoxide formation are investigated by means of quantum mechanical electronic structure calculations. Optimized molecular geometries and harmonic vibrational frequencies are determined using density functional theory (DFT). Insight into how the addition of O2 to linalool occurs is obtained by establishing a theoretical framework and systematically investigating three smaller systems: propene, 2-methyl-2-butene, and 2-methyl-2-pentene. 2-Methyl-2-pentene was chosen as a model system and used to compare with linalool. This theoretical study characterizes the linalool-O2 biradical intermediate state, which constitutes a branching point for the further oxidation reactions pathways. Thus, the observed linalool oxidation product spectrum is discussed in terms of a direct reaction path, the ene-type mechanism, and the radical mechanism. The major hydroperoxide found in experiments is 7-hydroperoxy-3,7-dimethyl-octa-1,5-diene-3-ol, and the calculated results support this finding.


Effects of root and stem extracts of Asparagus cochinchinensis on biochemical indicators related to aging in the brain and liver of mice.
Asparagus cochinchinensis is a traditional Chinese medicine used for treating lung and spleen-related diseases. In this study, we compared the medicinal effects of A. cochinchinensis root and stem extracts on the activity of superoxide dismutase (SOD), the content of malonaldehyde (MDA) and total protein content in the brain, liver and plasma of mice. Polysaccharides and aqueous extracts of the roots significantly increased the spleen index and the SOD activity but reduced the MDA content and slowed down the aging process. In contrast, feeding with the stem extracts significantly reduced the SOD activity and increased the MDA accumulation in the brain and liver of mice, suggesting that the stem extracts may not be appropriate for treating aging-related diseases.


Effectiveness of training general practitioners to improve the implementation of brief stop-smoking advice in German primary care: study protocol of a pragmatic, 2-arm cluster randomised controlled trial (the ABCII trial).
The German clinical guideline on tobacco addiction recommends that general practitioners (GPs) provide brief stop-smoking advice to their patients according to the "5A" or the much briefer "ABC" method, but its implementation is insufficient. A lack of training is one barrier for GPs to provide such advice. Moreover, the respective effectiveness of a 5A or ABC training regarding subsequent delivery of stop-smoking advice has not been investigated. We developed a training for GPs according to both methods, and conducted a pilot study with process evaluation to optimize the trainings according to the needs of GPs. This study aims at evaluating the effectiveness of both trainings. A pragmatic 2-arm cluster randomised controlled trial with a pre-post data collection will be conducted in 48 GP practices in North Rhine-Westphalia (Germany). GPs will be randomised to receive a 3.5-h-training in delivering either 5A or ABC, including peer coaching and intensive role plays with professional actors. The patient-reported primary outcome (receipt of GP advice to quit: yes/no) and secondary outcomes (recommendation rates of smoking cessation treatments, group comparison (5A versus ABC): receipt of GP advice to quit) will be collected in smoking patients routinely consulting their GP within 4 weeks prior, and 4 weeks following the training. Additional secondary outcomes will be collected at 4, 12 and 26 weeks following the consultation: use of cessation treatments during the last quit attempt (if so) since the GP consultation, and point-prevalence abstinence rates. The primary data analysis will be conducted using a mixed-effects logistic regression model with random effects for the cluster variable. If the training increases the rates of delivery of stop-smoking advice, it would offer a low-threshold strategy for the guideline implementation in German primary care. Should one method prove superior, a more specific guideline recommendation can be proposed. German Clinical Trials Register (DRKS00012786); registered on 22th August 2017, prior to the first patient in.


Screening Tool for Restrictive and Obstructive Ventilatory Abnormalities in a Population-Based Survey.
A 6 s spirometry with an inexpensive pocket spirometer efficiently selects individuals for a diagnostic-quality spirometry for airflow limitation, but could also be useful to identify individuals with a restrictive pattern. We evaluated an inexpensive simplified spirometer (chronic obstructive pulmonary disease [COPD]-6) as a screening tool to identify spirometric abnormalities. A population-based survey in Mexico City, with 742 participants performing pre- and post-BD spirometry and a three-maneuver 6 s spirometry (pre-BD) with a COPD-6. We evaluated forced expiratory volume in 1 s (FEV1), FEV6, and FEV1/FEV6 from the COPD-6, crude and expressed as the percentage of predicted (%P), to discriminate post-bronchodilator airflow obstruction (FEV1/forced vital capacity [FVC] < 5th percentile) or restriction (FVC or FEV1 <5th percentile with normal FEV1/FVC) through receiver operating characteristics and their area under the curve (AUC). FEV1%P was the best predictor to identify pre- and post-BD ventilatory abnormalities (best cutoff point 87%P, AUC 92% for restrictive pattern, 89% for obstructive pattern, and 91% for any spirometric abnormality). Deriving to clinical spirometry only those with < 87%P (26% of the sample) missed only 12% of spirometric abnormalities most of the latter mild. An FEV1 < 87%P from a pre-BD 6 s spirometry correctly identified individuals with spirometric ventilatory defects, either obstructive or restrictive.


Serotype specific polymerase chain reaction identifies a higher prevalence of streptococcus mutans serotype k and e in a random group of children with dental caries from the Southern region of India.
The development of dental caries has been associated with the oral prevalence of Streptococcus mutans. Four serotypes of S. mutans have been reported, namely serotype c, e, f, and k that are classified based on the composition and linkages of cell wall polysaccharides, response to physiological reactions, sero-specificity and 16s rRNA homology. Although the oral prevalence of S. mutans serotype c in Indian subjects with or without caries is known, the prevalence of the other three serotypes, e, f, and k are not known. Hence in this study, we have investigated the occurrence of the e, f, and k serotypes in children with or without caries within the age group of 6-12 years. Genomic DNA isolated from whole saliva of caries active (CA) and caries free (CF) groups were first screened for the presence of S. mutans by strain specific polymerase chain reaction (PCR). Those samples that tested positive for the presence of S. mutans were further analyzed by serotype specific PCR to identify the prevalence of the serotypes. Strain specific PCR indicated a higher prevalence of S. mutans in CA group (80%) relative to CF group (43%). Further analysis of the S. mutans positive samples in both groups indicated a higher prevalence of serotype k and e, followed by serotype f in CA group. The present data clearly establishes a novel S. mutans serotype prevalence hierarchy in children from this region, compared with those that have been reported elsewhere. Besides, the data are also clinically significant as the occurrence of serotype k has been associated with infective endocarditis.


Plasmofluidic-Based Near-Field Optical Trapping of Dielectric Nano-Objects Using Gold Nanoislands Sensor Chips.
Near-field optical manipulation has been widely used for guiding and trapping nanoscale objects close to an optical-active interface. This near-field manipulation opens opportunities for next-generation biosensing with the capability of large-area trapping and in situ detection. In this article, we used the finite element method (FEM) to analyze the motion mechanism of nano-objects (50-500 nm) in the near-field optics, especially localized surface plasmon resonance (LSPR). The size-dependent optical forces and hydrodynamic forces of subwavelength nanoparticles (<500 nm) in different hydrodynamic velocity fields were calculated. When the strength of the local electric field was increased, LSPR with two-dimensional gold nanoislands (AuNIs) showed improved capability for manipulating nano-objects near the vicinity of the AuNI interface. Through the experiments of in situ interferometric testing 50-500 nm nano-objects with constant number concentration or volume fraction, it was confirmed that the local plasmonic near-field was able to trap the dielectric polystyrene beads smaller than 200 nm. The plasmofluidic system was further verified by testing biological nanovesicles such as exosomes (40-200 nm) and high- and low-density lipoproteins (10-200 nm). This concept of direct dielectric nano-objects manipulation enables large-scale parallel trapping and dynamic sensing of biological nanovesicles without the need of molecular binding tethers or labeling.


Calculation of transition probability for neutralization process of +1 ion based on the Noziéres and Dominicis theory.
We investigate the neutralization probability of a +1 ion moving parallel to a metal surface, mainly using the Noziéres and Dominicis theory (ND theory), which was applied to the edge singularities in x-ray absorption and emission spectra in metals. In particular, we focus on the effects due to the sudden disappearance of the image potential in the neutralization process. From the analysis, we found that the neutralization probability is given by [Formula: see text], where D and Γ are the band width and the gamma function. The factor α = 2δ/π-(δ/π)(2) is given by the phase shift (δ: phase shift on Fermi surface), and the energy difference between the initial and final states, Δ, includes the kinetic energy of the ion and various other phenomenological factors. The singularity caused from the sudden disappearance of the image potential enhances or reduces the neutralization probability depending on the symmetry of atomic orbital of the ion. When the ion velocity is too fast to form an image potential, the neutralization process would proceed without the creation of an image potential, accompanying an excitation of a surface plasmon; as a result of plasmon excitation the ion velocity becomes slower than the plasma frequency because of screening effects. In this paper, we apply the ND theory to the case of slow ion motion and discuss the dynamics.


Ischemic maculopathy in patients with acquired immunodeficiency syndrome.
To describe the characteristics of ischemic maculopathy in patients with human immunodeficiency virus (HIV) infection, as a means of understanding this uncommon disorder more fully. This is a multicenter, retrospective review of clinical data available for five HIV-infected patients who were given the diagnosis of ischemic maculopathy. All cases had been diagnosed on the basis of fluorescein angiograms obtained after patients complained of vision loss. Four of the five patients had bilateral macular disease. Visual acuity at presentation in the nine affected eyes ranged from 20/20 to count fingers. Vision loss was gradual in both eyes of one patient and was abrupt in onset in seven eyes. Each of the seven eyes with abrupt vision loss had opacification of the superficial retina and/or intraretinal hemorrhages near the fovea. Fluorescein angiography revealed enlargement of the foveal avascular zone and mild staining of the juxtafoveal vessels in affected eyes. Six eyes had active or clinically inactive cytomegalovirus retinitis at presentation, and a seventh eye developed cytomegalovirus retinitis 2 weeks later. All patients were receiving anticytomegalovirus drugs when they developed visual symptoms. Visual acuity remained stable in five eyes, became worse in two eyes, and improved in two eyes; final visual acuity ranged from 20/25 to count fingers. Ischemic maculopathy may cause profound and permanent vision loss in HIV-infected individuals. Fluorescein angiography should be considered in all HIV-infected patients with unexplained loss of vision. The pathogenesis of ischemic maculopathy remains unknown.


Transformation of the dermatophyte Trichophyton mentagrophytes to hygromycin B resistance.
A transformation system for the ringworm-producing dermatophyte Trichophyton mentagrophytes has been developed. The system employs the plasmid pHIS, which contains a bacterial hygromycin B phosphotransferase gene linked to Cochliobolus heterostrophus regulatory sequences (B. G. Turgeon, R. C. Garber, and O. C. Yoder, Mol. Cell. Biol. 7:3297-3305, 1987). This plasmid confers hygromycin B resistance to T. mentagrophytes. The DNA was stably integrated into the fungal genome, and the number and sites of integrations varied among transformants. Transformant clones were capable of infecting guinea pigs. This system opens the way for the molecular genetic analysis of the interaction of T. mentagrophytes with epithelial animal tissues.


MOF@MOF: microporous core-shell architectures.
Mixing two different linkers with the same topology has been applied to make metal-organic frameworks (MOFs) either in one batch or sequentially to generate coordination copolymers with either a randomly mixed or a core-shell composition of linkers.


Effect of cycloheximide on the cell cycle of the crypts of the small intestine of the rat.
A single injection of 1.5 mg/kg of cycloheximide induces a complete disappearance of mitotic activity in rat intestinal crypts within 1.5-2 hr. No significant necrosis of crypt cells is observed even though this phenomenon is accompanied by a marked decrease in uptake of labeled precursors into protein and DNA. Mitoses reappear 6 hr after injection and recovery then follows a cyclic pattern over a period equivalent to one cell cycle, thereby reflecting at least a partial synchronization of cell division. Concurrent use of colchicine, an agent known to induce metaphase arrest, has demonstrated that cycloheximide, while having no apparent effect on cells already in division, prevents the entrance of new cells into visible mitosis. Analysis of the cell cycle suggests that one block initiated by cycloheximide occurs in G(2), presumably as the result of an interference with the formation of protein(s) required for the normal progression of cells from this phase of the cycle into mitosis.


Is thymocyte development functional in the aged?
T cells are an integral part of a functional immune system with the majority being produced in the thymus. Of all the changes related to immunosenescence, regression of the thymus is considered one of the most universally recognised alterations. Despite the reduction of thymic size, there is evidence to suggest that T cell output is still present into old age, albeit much diminished; leading to the assumption that thymocyte development is normal. However, current data suggests that recent thymic emigrant from the aged thymus are functionally less responsive, giving rise to the possibility that the generation of naïve T cell may be intrinsically impaired in the elderly. In light of these findings we discuss the evidence that suggest aged T cells may be flawed even before exiting to the periphery and could contribute to the age-associated decline in immune function.


Beperminogene perplasmid for the treatment of critical limb ischemia.
Therapeutic angiogenesis for the treatment of ischemic disease can be attained through the delivery of recombinant growth factor proteins, through gene transfer or cell transplantation. Gene transfer associated with adenovirus or naked plasmid DNAs has been extensively studied in clinical trials. An investigational product, beperminogene perplasmid, is the naked plasmid DNA encoding the cDNA of human HGF, which has potent angiogenic activity. In several clinical trials, beperminogene perplasmid showed favorable safety and efficacy profile in the treatment of critical limb ischemia. This article reviews the results of pre-clinical and clinical studies of beperminogene perplasmid in the treatment of critical limb ischemia caused by peripheral arterial disease and Buerger's disease.


Anomalous origin of the left anterior descending artery from the pulmonary artery associated with bicuspid aortic valve and aortic coarctation.
A 15-year-old boy presented with exertional palpitations and chest pain. Investigation revealed anomalous origin of his left anterior descending coronary artery from his pulmonary trunk causing myocardial ischaemia. He previously had aortic coarctation repair with known aortic root dilation and a bicuspid aortic valve. His left anterior descending artery was implanted into the aortic root using a Gortex interposition conduit. This represents an interesting combination of cardiac abnormalities for which repair required consideration of the requirement of further surgery in the future.


In Vivo Spinal Distribution of Cy5.5 Fluorescent Dye after Injection via the Lateral Ventricle and Cisterna Magna in Rat Model.
The purpose of this study was to find an optimal delivery route for clinical trials of intrathecal cell therapy for spinal cord injury in preclinical stage. We compared in vivo distribution of Cy5.5 fluorescent dye in the spinal cord region at various time points utilizing in vivo optical imaging techniques, which was injected into the lateral ventricle (LV) or cisterna magna (CM) of rats. Although CM locates nearer to the spinal cord than the LV, significantly higher signal of Cy5.5 was detected in the thoracic and lumbar spinal cord region at all time points tested when Cy5.5 was injected into the LV. In the LV injection Cy5.5 signal in the thoracic and lumbar spinal cord was observed within 12 hours after injection, which was maintained until 72 hours after injection. In contrast, Cy5.5 signal was concentrated at the injection site in the CM injection at all time points. These data suggested that the LV might be suitable for preclinical injection route of therapeutics targeting the spinal cord to test their treatment efficacy and biosafety for spinal cord diseases in small animal models.


[Nitrogen and phosphorus input from wet deposition in Taihu Lake region: a case study in Changshu Agro-ecological Experimental Station].
From June 2003 to May 2004, the precipitation at Changshu Agro-ecological Station (31 degrees 32'45" N, 120 degrees 41'57" E) of Chinese Academy of Sciences was collected to monitor its particle- and dissolved nitrogen and phosphorus concentrations, with the seasonal variation of nitrogen and phosphorus in wet deposition in Taihu Lake region investigated. The nitrogen input from wet deposition had an obvious seasonal variation, being higher in summer and spring and lower in autumn and winter. The ratios of dissolved nitrogen (DN) and particle nitrogen (PN) to total nitrogen (TN) in wet deposition were 88.2% and 11.8%, and those of dissolved phosphorus (DP) and particle phosphorus (PP) to total phosphorus (TP) were 53.3% and 46.7%, respectively. The amounts of nitrogen and phosphorus deposited into Taihu Lake region by light and medium precipitation were higher than those by heavy precipitation. The annual input of TN and TP from wet deposition was 30.2 kg x hm(-2) and 1.1 kg x hm(-2), respectively, and the DN concentration in all precipitation events as well as the DP concentration in 92.5% of precipitation events was higher than the thresholds of inland water eutrophication.


Periodontal health and serum, saliva matrix metalloproteinases in patients with mild chronic obstructive pulmonary disease.
The present case-control study aimed to evaluate comparatively the salivary and serum levels of matrix metalloproteinases (MMP)-8 and- 13 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in patients with mild chronic obstructive pulmonary disease (COPD) and non-COPD controls. Clinical periodontal measurements were recorded before any periodontal intervention in 36 patients with mild COPD and 20 non-COPD controls admitted to Ege University Department of Chest Diseases COPD outpatient clinic (İzmir, Turkey). Salivary and serum levels of MMP-8, MMP-13, and TIMP-1 were determined by immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA). Data were analyzed with non-parametric statistical tests. Patients with COPD were significantly older than the control group (p < 0.05). The COPD group showed significantly higher serum levels of MMP-8 IFMA, MMP-8/TIMP-1 IFMA than the control group (p < 0.005). By ELISA, serum MMP-8, MMP-8/TIMP-1, TIMP-1, and MMP-13 levels were similar in both groups (p > 0.05). Salivary MMP-8, MMP-13, and TIMP-1 levels were similar in both groups (p > 0.05). The present findings suggest that immunodetection of MMP-8 is dependent on the selected techniques and even with mild COPD some systemic inflammatory markers such as MMP-8 tend to increase. However, the present clinical periodontal and biochemical findings do not provide support for the previously proposed interaction between COPD and periodontal diseases.


The 2-oxoglutarate dehydrogenase complex from Azotobacter vinelandii. 1. Molecular cloning and sequence analysis of the gene encoding the 2-oxoglutarate dehydrogenase component.
The nucleotide sequence of the gene encoding the 2-oxoglutarate dehydrogenase component (E1o) of the 2-oxoglutarate dehydrogenase complex from Azotobacter vinelandii has been determined. The protein-coding sequence consists of 2832 bp (944 codons, including the AUG start codon and the UAA stop codon). The predicted molecular mass (105,687 Da) is in good agreement with that published for the isolated enzyme. The E1o gene is separated from the gene encoding the E2o component by a 42-bp intergenic region. No Escherichia-coli-like promoter sequences are found in the sequenced 97 bp upstream from the E1o gene. A putative ribosome-binding site is located 10-16 bp upstream from the start codon of the E1o gene. No terminator sequences could be detected downstream from the stop codon. Together with the identical situation for the E2o gene and the presence of terminating sequences downstream of the E3 gene, it can be assumed that all three genes of the 2-oxoglutarate dehydrogenase multienzyme complex are transcribed as a single mRNA transcript under the control of a promoter, located more than 100 bp upstream of the E1o gene, analogous to the pyruvate dehydrogenase complex in E. coli. The similarity with the sucA gene of E. coli is high with 59% identity.


Effect of advanced maternal age on pregnancy outcomes: a single-centre data from a tertiary healthcare hospital.
The aim of this study was to assess the effect of advanced maternal age on pregnancy and neonatal outcomes in patients attending a tertiary centre hospital. Between January 2013 and December 2016, the records of all patients who were referred for pregnancy follow-ups and delivery were retrospectively reviewed and were divided according to their parity and age. Patients over 35 years old were categorised as advanced maternal age; (1) 35-40 years old. (2) 40-45 years old. (3) 45 years and over. Most of the prenatal complications were found to increase in the advanced maternal age group. The caesarian section rate was found to be higher in all advanced maternal age groups. There was no significant relationship between 5 Minute Apgar scores of <7 and perinatal mortality and post-term pregnancy and parity. Globally, advanced maternal age pregnancy shows an increase as a result pregnancy complication will increase. It is important to make a appropriate follow-up for pregnancies of advance maternal age mothers. Impact statement What is already known on this subject? Advanced maternal age is a poor prognostic factor for pregnancy outcomes. But there remains no consensus opinion or a plan for the management of pregnancy in this particular risk group. What do the results of this study add? This clinical study makes a contribution to the literature for advanced maternal age and pregnancy complications. This study is one of the few studies emphasising the importance of parity in advanced maternal age and the relationship between first trimester pregnancy complications and advanced maternal age. What are the implications of these findings for clinical practice and/or further research? After the ART pregnancies increasing all around the world not only advanced age but the parity become an important role. Due to an increase in advanced maternal age pregnancies in all around the world, we think that better understanding and management of the complications to be encountered in advanced maternal age and parity pregnancies will be appropriate.


Modifications induced by ascorbic acid on alkaline phosphatase fluorescence.
Ascorbic acid, isoascorbic acid and dehydroascorbic acid quench the tryptophyl fluorescence of alkaline phosphatase. The quenching is protein aspecific, although its extent reflects the different inhibitory efficiency of the compounds. The kinetic inactivation and emission deactivation of alkaline phosphatase isoenzymes present also striking similarities. The fluorescence modifications, moreover, show a particular pattern, indicative of a transition phenomenon. The quenching effects displayed by the ascorbic system on alkaline phosphatase can then supply an interesting insight into other aspects of the inhibitor-enzyme interaction.


Reduced CD160 Expression Contributes to Impaired NK-cell Function and Poor Clinical Outcomes in Patients with HCC.
: We previously reported that deficiencies in natural killer (NK)-cell number and function play an important role in the progression of hepatocellular carcinoma (HCC). However, the mechanisms underlying this phenomenon remain obscure. In this study, we analyzed the expression of CD160 on intrahepatic NK cells by evaluating peritumoral and intratumoral tissues of 279 patients with HCC and 20 healthy livers. We observed reduced expression of CD160 on intratumoral NK cells, and patients with lower CD160 cell densities within tumors exhibited worse disease and a higher recurrence rate. High-resolution microarray and gene set enrichment analysis of flow cytometry-sorted primary intrahepatic CD160+ and CD160- NK cells of healthy livers indicated that human CD160+ NK cells exhibited functional activation, high IFNγ production, and NK-mediated immunity. In addition, global transcriptomic analysis of sorted peritumoral and intratumoral CD160+ NK cells revealed that intratumoral CD160+ NK cells are more exhausted than peritumoral CD160+ NK cells and produce less IFNγ. High levels of TGFβ1 interfered with production of IFNγ by CD160+ NK cells, blocking of which specifically restored IFNγ production in CD160+ NK cells to normal levels. These findings indicate that reduced numbers of CD160+ NK cells, together with the functional impairment of CD160+ NK cells by TGFβ1, contribute to tumor immune escape. In addition, restoring the expression of CD160 and blocking TGFβ1 appear a promising therapeutic strategy against liver cancer. SIGNIFICANCE: These findings show that reduced number and function of CD160+ NK cells in the tumor microenvironment contributes to immune escape of HCC; blocking TGFβ1 restores IFNγ production of CD160+ NK cells.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/23/6581/F1.large.jpg.


Biological Evaluation of Graphene Quantum Dots and Nitrogen-Doped Graphene Quantum Dots as Neurotrophic Agents.
Over time, developments in nano-biomedical research have led to the creation of a number of systems to cure serious illnesses. Tandem use of nano-theragnostics such as diagnostic and therapeutic approaches tailored to the individual disease treatment is crucial for further development in the field of biomedical advancements. Graphene has garnered attention in the recent times as a potential nanomaterial for tissue engineering and regenerative medicines owing to its biocompatibility among the several other unique properties it possesses. The zero-dimensional graphene quantum dots (GQDs) and their nitrogen-doped variant, nitrogen-doped GQDs (N-GQDs), have good biocompatibility, and optical and physicochemical properties. GQDs have been extensively researched owing to several factors such as their size, surface charge, and interactions with other molecules found in biological media. This work briefly elucidates the potential of electroactive GQDs as well as N-GQDs as neurotrophic agents. In vitro investigations employing the N2A cell line were used to evaluate the effectiveness of GQDs and N-GQDs as neurotrophic agents, wherein basic investigations such as SRB assay and neurite outgrowth assay were performed. The results inferred from immunohistochemistry followed by confocal imaging studies as well as quantitative real-time PCR (qPCR) studies corroborated those obtained from neurite outgrowth assay. We have also conducted a preliminary investigation of the pattern of gene expression for neurotrophic and gliotrophic growth factors using ex vivo neuronal and mixed glial cultures taken from the brains of postnatal day 2 mice pups. Overall, the studies indicated that GQDs and N-GQDs hold prospect as a framework for further development of neuroactive compounds for relevant central nervous system (CNS) purposes.


Identification of Bile Salt Hydrolase and Bile Salt Resistance in a Probiotic Bacterium Lactobacillus gasseri JCM1131T.
Lactobacillus gasseri is one of the most likely probiotic candidates among many Lactobacillus species. Although bile salt resistance has been defined as an important criterion for selection of probiotic candidates since it allows probiotic bacteria to survive in the gut, both its capability and its related enzyme, bile salt hydrolase (BSH), in L. gasseri is still largely unknown. Here, we report that the well-known probiotic bacterium L. gasseri JCM1131T possesses BSH activity and bile salt resistance capability. Indeed, this strain apparently showed BSH activity on the plate assay and highly tolerated the primary bile salts and even taurine-conjugated secondary bile salt. We further isolated a putative BSH enzyme (LagBSH) from strain JCM1131T and characterized the enzymatic function. The purified LagBSH protein exhibited quite high deconjugation activity for taurocholic acid and taurochenodeoxycholic acid. The lagBSH gene was constitutively expressed in strain JCM1131T, suggesting that LagBSH likely contributes to bile salt resistance of the strain and may be associated with survival capability of strain JCM1131T within the human intestine by bile detoxification. Thus, this study first demonstrated the bile salt resistance and its responsible enzyme (BSH) activity in strain JCM1131T, which further supports the importance of the typical lactic acid bacterium as probiotics.


Incorporation of metallocenes into the channel structured Metal-Organic Frameworks MIL-53(Al) and MIL-47(V).
A selection of metallocene inclusion compounds with channel structured MOFs (MOF = Metal-Organic Framework) were obtained via solvent-fee adsorption of the metallocenes from the gas-phase. The adsorbate structures ferrocene(0.5)@MIL-53(Al) (MIL-53(Al) = [Al(OH)(bdc)](n) with bdc = 1,4-terephthalate), ferrocene(0.25)@MIL-47(V) (MIL-47(V) = [V(O)(bdc)](n)), cobaltocene(0.25)@MIL-53(Al), cobaltocene(0.5)@MIL-47(V), 1-formylferrocene(0.33)@MIL-53(Al), 1,1'dimethylferrocene(0.33)@MIL-53(Al), 1,1'-diformylferrocene(0.5)@MIL-53(Al) were determined from powder X-ray diffraction data and were analyzed concerning the packing and orientation of the guest species. The packing of the ferrocene guest molecules inside MIL-47(V) is significantly different compared to MIL-53(Al) due to the lower breathing effect and weaker hydrogen bonds between the guest molecules and the host network in the case of MIL-47(V). The orientation of the metallocene molecule is also influenced by the substituents (CH(3) and CHO) at the cyclopentadienyl ring and the interaction with the bridging OH group of MIL-53(Al). The inclusion of redox active cobaltocene into MIL-47(V) leads to the formation of a charge transfer compound with a negatively charged framework. The reduction of the vanadium centers is stoichiometric. The resulting material is a mixed valence compound with a V(3+)/V(4+) ratio of 1:1. The new compounds were characterized via thermal gravimetric analysis, infrared spectroscopy, solid state NMR, and differential pulse voltammetry. Both systems are 1D-channel pore structures. The metallocene adsorbate induced breathing effect of MIL-53(Al) is more pronounced compared to MIL-47(V), this can be explained by the different bridging groups between the MO(6) clusters.


Evidence for a radical mechanism in peroxidase-catalyzed coupling. I. Steady-state experiments with various peroxidases.
Biosynthesis of thyroxine in the thyroid gland involves a reaction between two diiodotyrosyl residues within the same molecule of thyroglobulin, a large, thyroid-specific glycoprotein. This reaction, generally referred to as the coupling reaction, is catalyzed in the thyroid by the heme-containing glycoprotein enzyme, thyroid peroxidase, also a thyroid-specific protein. The coupling reaction is, however, not specific for thyroid peroxidase; it is also efficiently catalyzed by other heme-containing peroxidases. Peroxidase-catalyzed coupling may also occur between a monoiodotyrosyl and a diiodotyrosyl residue in thyroglobulin to form the more potent thyroid hormone, 3',3,5-triiodothyronine. Under most conditions, thyroxine formation in the thyroid is greatly favored over that of 3',3,5-triiodothyronine. Two mechanisms have been proposed for the coupling reaction, a radical mechanism and an ionic mechanism. In this, and in the following paper, we present evidence favoring a radical mechanism. This view is bsed primarily on the observation that peroxidase-catalyzed coupling is markedly stimulated by substoichiometric concentrations of free diiodotyrosine (DIT). Evidence obtained in this and in the following paper leads us to conclude that the stimulatory effect of DIT on coupling involves peroxidase-catalyzed oxidation of the added DIT to a radical form. We propose that this stimulation involves a radical chain propagation mechanism. This implies that peroxidase-catalyzed coupling in the absence of DIT must also be a radical-mediated reaction.


Applicability of fluidized bed reactor in recalcitrant compound degradation through advanced oxidation processes: a review.
Treatment of industrial waste water (e.g. textile waste water, phenol waste water, pharmaceutical etc) faces limitation in conventional treatment procedures. Advanced oxidation processes (AOPs) do not suffer from the limits of conventional treatment processes and consequently degrade toxic pollutants more efficiently. Complexity is faced in eradicating the restrictions of AOPs such as sludge formation, toxic intermediates formation and high requirement for oxidants. Increased mass-transfer in AOPs is an alternate solution to this problem. AOPs combined with Fluidized bed reactor (FBR) can be a potential choice compared to fixed bed or moving bed reactor, as AOP catalysts life-span last for only maximum of 5-10 cycles. Hence, FBR-AOPs require lesser operational and maintenance cost by reducing material resources. The time required for AOP can be minimized using FBR and also treatable working volume can be increased. FBR-AOP can process from 1 to 10 L of volume which is 10 times more than simple batch reaction. The mass transfer is higher thus the reaction time is lesser. For having increased mass transfer sludge production can be successfully avoided. The review study suggests that, optimum particle size, catalyst to reactor volume ratio, catalyst diameter and liquid or gas velocity is required for efficient FBR-AOP systems. However, FBR-AOPs are still under lab-scale investigation and for industrial application cost study is needed. Cost of FBR-AOPs highly depends on energy density needed and the mechanism of degradation of the pollutant. The cost of waste water treatment containing azo dyes was found to be US$ 50 to US$ 500 per 1000 gallons where, the cost for treating phenol water was US$ 50 to US$ 800 per 1000 gallons. The analysis for FBR-AOP costs has been found to depend on the targeted pollutant, degradation mechanism (zero order, 1st order and 2nd order) and energy consumptions by the AOPs.


Improving accuracy for stereotactic body radiotherapy treatments of spinal metastases.
Use of SBRT techniques is now a relatively common recourse for spinal metastases due to good local control rates and durable pain control. However, the technique has not yet reached maturity for gantry-based systems, so work is still required in finding planning approaches that produce optimum conformity as well as delivery for the slew of treatment planning systems and treatment machines. A set of 32 SBRT spine treatment plans based on four vertebral sites, varying in modality and number of control points, were created in Pinnacle. These plans were assessed according to complexity metrics and planning objectives as well as undergoing treatment delivery QA on an Elekta VersaHD through ion chamber measurement, ArcCheck, film-dose map comparison and MLC log-file reconstruction via PerFraction. All methods of QA demonstrated statistically significant agreement with each other (r = 0.63, P < 0.001). Plan complexity and delivery accuracy were found to be independent of MUs (r = 0.22, P > 0.05) but improved with the number of control points (r = 0.46, P < 0.03); with use of 90 control points producing the most complex and least accurate plans. The fraction of small apertures used in treatment had no impact on plan quality or accuracy (r = 0.29, P > 0.05) but rather more complexly modulated plans showed poorer results due to MLC leaf position inaccuracies. Plans utilizing 180 and 240 control points produced optimal plan coverage with similar complexity metrics to each other. However, plans with 240 control points demonstrated slightly better delivery accuracy, with fewer MLC leaf position discrepancies. In contrast to other studies, MU had no effect on delivery accuracy, with the most impactful parameter at the disposal of the planner being the number of control points utilized.


N-ethylmaleimide increases the L-type calcium current in guinea-pig ventricular myocytes.
The effects of the alkylating agent N-ethylmalemide (NEM) on the L-type Ca current (ICa) of guinea-pig ventricular myocytes were studied with the whole-cell voltage-clamp technique at 21-23 degrees C. NEM (50-100 microM) produced an increase in ICa comparable to that produced by cAMP-increasing agents (isoprenaline, forskolin, phosphodiesterase inhibitors). The effects of NEM on ICa were not additive with those of the phosphodiesterase blockers papaverine and isobutylmethylxanthine. They were neither suppressed nor prevented by carbachol (100 microM) and could also not be prevented by pertussis toxin treatment or by cell dialysis with GDP beta S (300 microM) or GTP gamma S (300 microM). NEM, at low concentration (50 microM), increased twitch contraction measured in right ventricular strips. At a higher concentration (> or = 100 microM), this effect was followed by a decrease of the twitch and an increase in basal tension. It is proposed that NEM acts by transiently increasing cAMP levels to increase ICa and the twitch. Our experiments are not consistent with a mechanism involving Gi inhibition for NEM effect.


Toxicology of Astragalus lusitanicus Lam.
Astragalus lusitanicus is a toxic legume grown in Morocco and in some other Mediterranean countries. In small ruminants, poisoning by this plant is dominated by nervous signs characterized by many cycles of excitement-depression. Macroscopic examination of poisoned animals showed congestive lesions and oedema in the brain and lungs. Microscopic lesions consisted mainly of vacuolar degeneration in neurons, hepatocytes and in spleen and kidney cells. Serum activity of AST and CK as well as blood glucose and urea were increased as a result of poisoning. However, serum activity of alpha-mannosidase was not modified as is the case in locoism. Chemical investigations showed that A. lusitanicus does not contain swainsonine or miserotoxin and its selenium concentration is very low. However, this legume contains indolizidin alkaloids and a first compound was purified and identified.


Chemical Reactivity and Spectroscopy Explored From QM/MM Molecular Dynamics Simulations Using the LIO Code.
In this work we present the current advances in the development and the applications of LIO, a lab-made code designed for density functional theory calculations in graphical processing units (GPU), that can be coupled with different classical molecular dynamics engines. This code has been thoroughly optimized to perform efficient molecular dynamics simulations at the QM/MM DFT level, allowing for an exhaustive sampling of the configurational space. Selected examples are presented for the description of chemical reactivity in terms of free energy profiles, and also for the computation of optical properties, such as vibrational and electronic spectra in solvent and protein environments.