Efficacy and tolerance of second-generation antipsychotics in anorexia nervosa: A systematic scoping review.
Second-generation antipsychotics (SGAs) are frequently prescribed for the treatment of resistant anorexia nervosa. However, few clinical trials have been conducted so far and no pharmacological treatment has yet been approved by the Food and Drug Administration. The aim of this paper is to conduct a systematic scoping review exploring the effectiveness and safety of atypical antipsychotics in anorexia nervosa (AN). We conducted a systematic scoping review of the effectiveness and tolerability of SGAs in the management of AN. We included articles published from January 1, 2000, through September 12, 2022 from the PubMed and PsycInfo databases and a complementary manual search. We selected articles about adolescents and adults treated for AN by four SGAs (risperidone, quetiapine, aripiprazole or olanzapine). This work complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRIMA-ScR) and was registered in the Open Science Framework (OSF) repository. This review included 55 articles: 48 assessing the effectiveness of SGAs in AN and 7 focusing only on their tolerability and safety. Olanzapine is the treatment most frequently prescribed and studied with 7 randomized double-blind controlled trials. Other atypical antipsychotics have been evaluated much less often, such as aripiprazole (no randomized trials), quetiapine (two randomized controlled trials), and risperidone (one randomized controlled trial). These treatments are well tolerated with mild and transient adverse effects in this population at particular somatic risk. Limitations prevent the studies both from reaching conclusive, reliable, robust, and reproducible results and from concluding whether or not SGAs are effective in anorexia nervosa. Nonetheless, they continue to be regularly prescribed in clinical practice. International guidelines suggest that olanzapine and aripiprazole can be interesting in severe or first-line resistant clinical situations.


Nuclear techniques in nutrition and health: importance and applications in developing regions.
Nuclear and isotope methods in one form or another are regarded as essential tools for carrying out nutrition research besides enhancing sensitivity of nutrition monitoring techniques. They have been used extensively in industrialized countries to analyse human energy requirements, body composition including bone mineral density, and the metabolism of important nutrients such as protein, fat, vitamins and minerals. The information acquired has led to many improvements in nutrition and health. Currently, several strategic applications of isotopic techniques are being introduced in developing countries where they can benefit millions through monitoring improvement in nutritional status, and serve as specific indicators of broader social and economic advances.


Targeted methods for quantitative analysis of protein glycosylation.
Quantification of proteins by LC-MS/MS-MRM has become a standard method with broad projected clinical applicability. MRM quantification of protein modifications is, however, far less utilized, especially in the case of glycoproteins. This review summarizes current methods for quantitative analysis of protein glycosylation with a focus on MRM methods. We describe advantages of this quantitative approach, analytical parameters that need to be optimized to achieve reliable measurements, and point out the limitations. Differences between major classes of N- and O-glycopeptides are described and class-specific glycopeptide assays are demonstrated.


Response of antioxidative enzymes and apoplastic bypass transport in Thlaspi caerulescens and Raphanus sativus to cadmium stress.
A hydroponics experiment using hyperaccumulator Thlaspi caerulescens (alpine pennycress) and non-specific accumulator Raphanus sativus (common radish) was conducted to investigate the short-term effect of increasing Cd concentrations (0, 25, 50, 75, 100 microM) on metal uptake, chlorophyll content, antioxidative enzymes, and apoplastic bypass flow. As expected, T. caerulescens generally showed better resistance to metal stress, which was reflected by higher Cd accumulation within plant tissues with no signs of chlorosis, or wilt. Glutathione reductase (GR) and superoxide dismutase (SOD) activities in fresh leaves were monitored as the plant metal-detoxifying response. In general, both plant species exhibited an increase trend of GR activity before declining at 100 microM likely due to excessive levels of phytotoxic Cd. SOD activity exhibited almost a similar variation pattern to GR and decreased also at 100 microM Cd. For both plant species, fluorescent PTS uptake (8-hydroxy-1,3,6-pyrenetrisulphonic acid) increased significantly with metal level in exposure solutions indicating that Cd has a comparable effect to drought or salinity in terms of the gain of relative importance in apoplastic bypass transport under such stress conditions.


[Influence of indole-3-alkanecarboxylic acids on glucose utilization in rats].
The influence of various indole-3-alkane-carboxylic acids (indole-3-propionic acid, indole-3-butyric acid and derivatives of this substance) on some parameters of carbohydrate, fat and insulin metabolism were studied in normal and experimentally induced diabetic rats. Earlier it had been shown, by Schillinger and Loge (1973) using rat liver slices for in vitro studies and adrenalectomized rates for in vivo experiments that indole-3-butyric acid and its analogues investigated suppress gluconeogenesis from pyruvate and that these substances have a hypoglycaemic effect when administered orally at doses of 50-250 mg/kg. Indole-3-propionic acid, indole-3-butyric acid, 1-methyl-indole-3-butyric acid, 2-methyl-indole-3-butyric acid and 1-carboxy-6-fluor-1,2,3,4-tetrahydrocarbazol, administered orally at doses up to 1000 mg/kg, had either only a slight or no hypoglycaemic effect at all in intact and streptozotocin-diabetic rats. The suppression of gluconeogenesis observed in vitro thus only has an appreciable effect on blood glucose in vivo when the capacity of the liver to synthetize glucose is reduced. In normal rats indole-3-propionic acid and indole-3-butyric acid led to a deterioration of glucose tolerance following i.v. glucose loading and to a reduction of 14C-U-glucose oxidation. An increase in the concentration of serum free fatty acids (FFA) measured after treatment with indole-3-butyric acid and its 1- and 2-methylated derivatives was not--in accordance with a theory of an interference of the glucose and fatty acid utilization published in literature--considered to be the primary cause since the reduced formation of 14CO2 from radioactive glucose is not normalized when the increased FFA content is reduced by an inhibitor of lipolysis (5-methyl-isoxazol-3-carboxylic acid)...


Interleukin 3 and schizophrenia: the impact of sex and family history.
Chromosome 5q21-33 has been implicated in harboring risk genes for schizophrenia. In this paper, we report evidence that multiple single nucleotide polymorphisms in and around interleukin 3 (IL3) are associated with the disease in the Irish Study of High-Density Schizophrenia Families (ISHDSF), the Irish Case-Control Study of Schizophrenia (ICCSS) and the Irish Trio Study of Schizophrenia (ITRIO). The associations are sex-specific and depend on the family history (FH) of schizophrenia. In all three samples, rs31400 shows female-specific and FH-dependent associations (P=0.0062, 0.0647 and 0.0284 for the ISHDSF, ICCSS and ITRIO, respectively). Several markers have similar associations in one or two of the three samples. In haplotype analyses, identical risk and protective haplotypes are identified in the ISHDSF and ITRIO samples in several multimarker combinations. For ICCSS, the same haplotypes are implicated; however, the risk haplotypes observed in the family samples become protective. Several significant markers, rs440970, rs31400 and rs2069803, are located in and around known estrogen response elements, promoter and enhancer of the IL3 gene. They may explain the sex-specific associations and be functional for the expression of IL3 gene.


Selegiline increases heme oxygenase-1 expression and the cytotoxicity produced by dopamine treatment of neuroblastoma SK-N-SH cells.
Increased dopamine catabolism may be associated with oxidative stress and neuronal cell death in Parkinson's disease. The present study was carried out to examine the effect of dopamine on the expression of heme oxygenase-1 and -2 (HO-1 and HO-2) in human neuroblastomas (SK-N-SH cell line) and the effects of selegiline and antioxidants on this expression. Cells were kept with close control of pH and were incubated with varying concentrations of dopamine (0.1-100 microM) for 24 h. HO-1 and HO-2 cDNA probes were prepared by reverse transcription-polymerase chain reaction amplification. The mRNA expression of HO-1 and HO-2 was measured by Northern blot analysis. The levels of HO-1 mRNA increased after dopamine treatment, in a dose-dependent manner, in all cell lines studied, whereas levels of the two HO-2 transcripts did not. The HO-1 and HO-2 protein expression was analyzed by Western blotting. HO-1 protein was undetectable in untreated SK-N-SH cells and increased after treatment with dopamine. In contrast, the HO-2 protein (36 kDa) was detected in untreated cells and the levels did not change as a result of treatment. Alpha-tocopherol (10-100 microM) and ascorbic acid (100 microM) did not attenuate the effects of dopamine. Selegiline (10 microM) produced significant increase (P < 0.01) in the induction of HO-1 by dopamine (more than six times the control values). The increased expression of HO-1 following dopamine treatment indicates that dopamine produces oxidative stress in this cell line.


Indolylarylsulfones carrying a heterocyclic tail as very potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors.
We synthesized new indolylarylsulfone (IAS) derivatives carrying a heterocyclic tail at the indole-2-carboxamide nitrogen as potential anti-HIV/AIDS agents. Several new IASs yielded EC50 values <1.0 nM against HIV-1 WT and mutant strains in MT-4 cells. The (R)-11 enantiomer proved to be exceptionally potent against the whole viral panel; in the reverse transcriptase (RT) screening assay, it was remarkably superior to NVP and EFV and comparable to ETV. The binding poses were consistent with the one previously described for the IAS non-nucleoside reverse transcriptase inhibitors. Docking studies showed that the methyl group of (R)-11 points toward the cleft created by the K103N mutation, different from the corresponding group of (S)-11. By calculating the solvent-accessible surface, we observed that the exposed area of RT in complex with (S)-11 was larger than the area of the (R)-11 complex. Compounds 6 and 16 and enantiomer (R)-11 represent novel robust lead compounds of the IAS class.


Dihydroartemisinin attenuates autoimmune thyroiditis by inhibiting the CXCR3/PI3K/AKT/NF-κB signaling pathway.
Dihydroartemisinin (DHA) is the first generation of naturally occurring artemisinin derivatives with antimalarial activity. Recent research showed that this drug also features immunosuppressive and anti-inflammatory properties. Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease with no available effective drug treatment. In this study, we investigated effects of DHA on AIT in vitro and in vivo. Results showed that DHA can visibly reduce antithyroglobulin antibody and thyroid peroxidase antibody levels and regulate T helper cells (Th) 1/Th2 imbalance of experimental AIT mice. DHA also dose-dependently suppressed proliferation of lymphocytes induced by lipopolysaccharide and concanavalin A. DHA inhibited binding of C-X-C chemokine ligand 10 (CXCL10) and its receptor (C-X-C motif) receptor 3 (CXCR3), thus inhibiting calcium flow. DHA can also reduce expression levels of PI3-kinase (PI3K), p-PI3K, protein kinase B (AKT), p-AKT, nuclear factor (NF)-κB/p65, and p-NF-κB/p65. In conclusion, DHA may serve as treatment drug for AIT by inhibiting the CXCR3/PI3K/AKT/NF-kB signaling pathway.


PSEUDOBULBAR AFFECT IN MULTIPLE SCLEROSIS PATIENTS.
The aim of the study was to determine the prevalence of pseudobulbar affect (PBA) in patients with multiple sclerosis (MS) and to analyze the link between PBA and patient age, sex, clinical course of MS, disease duration and degree of disability. The study was conducted on 79 MS patients that underwent inpatient rehabilitation at the Lipik Special Hospital for Medical Rehabilitation in the period from August 15, 2014 to February 15, 2015. PBA is a term used for an emotional disinhibition syndrome characterized by sudden and involuntary episodes of crying or laughing which are not in proportion to the stimulus applied or occur without stimulus. The condition can be present in patients with various neurological disorders, such as amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, patients having recovered from stroke, or following traumatic brain injury. The estimated prevalence in patients with MS ranges from 10% to 46.2%. As a measuring instrument in the study, we used the Center for Neurologic Study-Lability Scale (CNS-LS), where a sum 17 denoted positive finding. The total number of respondents was 79, of which 33 (41.8%) met the CNS-LS criteria for the diagnosis of PBA. There was no statistically significant correlation between PBA, age and degree of disability, although PBA was more common in women and in patients with a secondary progressive form of the disease. We found that 42.4% of respondents with positive CNS-LS criteria for PBA did not inform their neurologist on the presence of sudden mood changes. The high frequency of PBA and the fact that a significant proportion of patients did not inform the neurologist on their affective disturbances call for an active approach to diagnosis and treatment.


Sum-frequency generation at interfaces: A Fresnel story. II. Analytical expressions for multilayer systems.
The well-known formalism for Sum-Frequency Generation (SFG) reflected or transmitted by a three-layer system involves three equations defining the emitted SFG intensity, the effective nonlinear susceptibility, and a set of Fresnel factors specific to the three-layer system. We generalize the equations to an N-layer system, where all media have non-vanishing thicknesses, by leaving the first two equations unchanged and modifying only the Fresnel factors. These universal Fresnel factors bear all the complexity of light propagation and interference in the system, in amplitude and phase. They are analytically known anywhere in the N-layer system, either at any interface or in any of the bulks, and share common expressions for the three beams, incoming or emitted, of the SFG process in reflection. Enclosing an ultrathin layer (e.g., a molecular monolayer) in the system does not modify the Fresnel factors except for boundary conditions at this layer, as in the three-layer case. Specific rules are elaborated to simplify systems containing macroscopic layers. Equations for the four- and five-layer systems are explicitly provided. Simulations in the four-layer system allow for the recovery of the results of the transfer matrix formalism at a lower complexity cost for SFG users. Finally, when several interfaces in the system produce SFG signals, we show that it is possible to probe only the most buried one by canceling all the SFG responses except at this last interface, generalizing the results of the three-layer system.


The desensitization of the transient receptor potential vanilloid 1 by nonpungent agonists and its resensitization by bradykinin.
Transient receptor potential vanilloid type-1 (TRPV1) channels have crucial roles in inflammatory hyperalgesia. Different inflammatory mediators can modulate TRPV1 sensitization. Bradykinin is an algogenic substance released at the site of inflammation. The aim of the present study is to investigate the desensitization of TRPV1 receptor by nonpungent agonists and to determine how bradykinin and prostaglandin E2 receptors (EP3 and EP4) modulate the resensitization of TRPV1 receptor after being desensitized by nonpungent agonists. Tail flick test was used to investigate capsaicin-induced thermal hyperalgesia and the desensitization of TRPV1 by the nonpungent agonists (olvanil and arvanil) in male BALB/c mice weighed (22-25 g). Resensitization of TRPV1 by bradykinin and the role of prostaglandin receptors in mediating sensitization of TRPV1 were also investigated. Intraplantar injection of capsaicin (0.3 µg) produced a robust thermal hyperalgesia in mice, while olvanil (0.3 µg) or arvanil (0.3 µg) produced no hyperalgesia, emphasizing their lack of pungency. Olvanil and arvanil significantly attenuated capsaicin-induced thermal hyperalgesia in mice. Bradykinin significantly reversed the desensitizing effects of arvanil, but not olvanil. EP4 but not EP3 receptors mediate the sensitization of TRPV1 By bradykinin in vivo. The present study provides evidence for a novel signaling pathway through which bradykinin can regulate the TRPV1 ion channel function via EP4 receptor.


Hepatocellular carcinoma: diagnosis and treatment.
Hepatocellular carcinoma is the most frequent primary malignancy of the liver and appears to be rising in incidence in the United States and other developed western countries. Imaging studies play a key role in diagnosis of hepatocellular carcinoma, and more and more commonly, patients are being diagnosed at an asymptomatic stage. The use of triphasic computed tomography scanning and improved magnetic resonance imaging equipment and protocols has led to greater sensitivity and specificity for these techniques in diagnosis of hepatocellular carcinoma. Accurate staging of hepatocellular carcinoma is important in determining prognosis and in helping decide the best treatment for each patient. No one staging system appears optimal, but important factors to be considered are the size of the tumor, severity of underlying liver disease, and the functional status of the patient. Liver transplantation has grown in importance as a treatment for hepatocellular carcinoma but may be limited by availability of donor organs and long waiting times. This situation may be improved by greater use of living donor liver transplantation. Hepatic resection remains an important treatment modality for hepatocellular carcinoma, particularly in the absence of cirrhosis. Tumor ablation by alcohol injection or radiofrequency ablation is associated with favorable outcomes and may be considered a potentially curative treatment. Early diagnosis of hepatocellular carcinoma remains a key goal in improving the poor prognosis of this form of liver cancer. Identifying hepatocellular carcinoma at an early stage is often associated with having better treatment options for patients with small, asymptomatic tumors.


Idiopathic spinal cord herniation.
Idiopathic spinal cord herniation (ISCH) is a rare cause of progressive myelopathy. This condition has recently seen an increased frequency of diagnosis, possibly due to increased awareness and the use of magnetic resonance (MR) imaging. ISCH is characterised by herniation of the thoracic spinal cord through an anterior or anterolateral dural defect. Patients usually present with a Brown-Séquard-like syndrome, which is gradually progressive and may evolve into severe paraparesis. This disease has a characteristic radiological appearance, and in most cases, excellent postsurgical outcome. We report ISCH and its imaging appearance in a 31-year-old woman with classical presentation, and discuss the current concepts regarding the aetiopathogenesis, radiological features and management of the disease.


Time-dependent thermocontrol of the hydrophilic and lipophilic properties of DNA oligonucleotide prodrugs.
This unit describes the preparation of alkylthioalkylated and formamidoalkylated alcohols, an amidoalkylated alcohol, a hydroxylalkylated phosphoramidate, and their phosphoramidothioate derivatives, all of which have been identified as heat-sensitive thiophosphate-protecting groups in the development of thermolytic immunostimulatory DNA prodrugs. The alcohols are converted to their deoxyribonucleoside phosphoramidite derivatives, which are then used in the preparation of thermosensitive dinucleoside phosphorothioates. The thiophosphate-protecting groups of these dinucleoside phosphorothioates presumably undergo thermolytic cyclodeesterification at elevated temperature under essentially neutral conditions to release the desired phosphorothioate diester function. On the basis of their thermolytic deprotection kinetics, one can identify those thiophosphate-protecting groups that (i) may be useful for thiophosphate protection of CpG motifs of immunostimulatory DNA oligonucleotides (CpG ODNs); (ii) are suitable for protection of phosphodiester functions flanking the CpG motifs; and (iii) offer adequate protection of terminal phosphodiester functions against ubiquitous extracellular and intracellular exonucleases that may be found in biological environments.


ADRP/adipophilin is degraded through the proteasome-dependent pathway during regression of lipid-storing cells.
Adipose differentiation-related protein (ADRP) is a major protein associated with lipid droplets in various types of cells, including macrophage-derived foam cells and liver cells. However, the role of ADRP in the processes of formation and regression of these cells is not understood. When J774 murine macrophages were incubated with either VLDL or oleic acid, their content of both ADRP and triacylglycerol (TG) increased 3- to 4-fold. Induction of ADRP during TG accumulation was also observed in oleic acid-treated HuH-7 human liver cells. Addition of triacsin C, a potent inhibitor of acyl-CoA synthase, for 6 h decreased the amount of TG in VLDL-induced foam cells and oleic acid-treated liver cells; it decreased the amount of ADRP protein in parallel, indicating the amount of ADRP reduced during regression of the lipid-storing cells. Addition of a proteasome inhibitor during triacsin C treatment abolished the ADRP decrease and accumulated polyubiquitinated ADRP. In addition, the proteasome inhibitor reversed not only the degradation of ADRP but also TG reduction by triacsin C. These results suggest that cellular amounts of ADRP and TG regulate each other and that the ubiquitin-proteasome system is involved in degradation of ADRP during regression of lipid-storing cells.


CMV amplifies T-cell redeployment to acute exercise independently of HSV-1 serostatus.
Latent cytomegalovirus (CMV) infection has been shown to alter the lymphocyte response to acute aerobic exercise, likely due to the corresponding increase in exercise-responsive memory CD8(+) T cells. It is unknown if latent infection with another herpesvirus, herpes simplex virus 1 (HSV-1), also plays a role in shaping the lymphocyte response to exercise. Thirty-two men (ages 39.3 ± 14.7 yr) counterbalanced by CMV and HSV-1 serostatus (positive/negative) cycled for 30 min at ∼80% peak power. Blood sampled before, immediately after, and 1 h after exercise was analyzed by flow cytometry for T-cell subset enumeration. In resting blood, HSV-1(+) had fewer lymphocytes, CD4(+) T cells, KLRG1(-) CD28(+) CD4(+) T cells, and CD45RA(-)CCR7(+)CD4(+) T cells than HSV-1(-), whereas CMV(+) had increased numbers of lymphocytes, CD8(+) T cells, KLRG1(+)CD28(-)CD4(+) and CD8(+) T cells, and CD45RA(+)CCR7(-)CD8(+) T cells and a lower CD4:CD8 T-cell ratio than CMV(-). After exercise, CMV(+) had a greater mobilization of CD8(+) T cells, KLRG1+CD28(-)CD4+ and CD8(+) T cells, and CD45RA+CCR7(-)CD8+ T cells independently of HSV-1 serostatus, as well as a greater egress of these subsets 1 h after exercise. HSV serostatus did not influence total CD8(+) T-cell response to exercise. The impact of latent CMV infection on the redeployment of T-cell subsets with exercise is independent of HSV-1 infection. This is most likely due to the unique ability of CMV to alter the composition of the memory T-cell pool in favor of exercise-responsive T-cell subsets.


Clinical studies of new material for portal vein embolization: comparison of embolic effect with different agents.
Study of he embolic materials is necessary to select those suitable for preoperative portal embolization which increases the safety of hepatectomy. Twenty-three patients with biliary tract cancer and hepatic tumor underwent portal embolization of the right portal vein. Four kinds of embolic materials were used. Gelatin sponge was used in 9, cyanoacrylate in 4, fibrin glue in 2, and gelatin sponge with polidocanol in 8 patients. The embolic effect in inducing hypertrophy as well as the surgical results were compared for different embolic agents. Left lobe hypertrophy was evaluated by computed tomography volume before and 2 weeks after portal embolization. With gelatin sponge, the volumetric increase was 21.9%, compared to 25% with cyanoacrylate, 13.5% with fibrin glue, and 35.3% for gelatin sponge with polidocanol. The volume increase of gelatin sponge with polidocanol was superior to those of other agents. In 18 of the 21 patients, hepatectomies with/without pancreaticoduodenectomy were performed. In 11 patients using the first 3 of the above-mentioned agents, 2 operative procedures were changed to limited hepatic resection, and 3 patients died of hepatic failure due to insufficient hypertrophy. Seven patients for whom gelatin sponge with polidocanol was used underwent the proposed operations with good results. Gelatin sponge with polidocanol induced sufficient hypertrophy and was the most suitable agent for portal embolization.


Effects of an antagonist of the bombesin/gastrin-releasing peptide receptor on complete Freund's adjuvant-induced arthritis in rats.
To determine the effects of RC-3095 in clinical and histopathologic parameters and inflammatory mediators on complete Freund's adjuvant-induced arthritis (CFA). The arthritis was induced by injection of CFA into the left hind footpad. The animals were divided into control, vehicle injected control, placebo group (saline subcutaneously 50ml/kg, once daily for 8 days after modeling), treatment group (0.3mg/kg of RC-3095 subcutaneously, once daily for 8 days after induction). Clinical evaluation was accomplished daily, through scoring of the paw edema. The animals were sacrificed 15 days after induction for collection of hind foot joints for histology. We used a histological scoring system which was previously described, and interferon (INF)-gamma, interleukin (IL)-1beta, tumor necrosis factor (TNF), interleukin (IL)-6 and interleukin (IL)-10 were measured by ELISA. There was a significant inhibition of joint histological findings in the RC-3095 treated group, including synovial inflammatory infiltration and hyperplasia, cartilage and bone erosion. IFN-gamma, IL-1beta, TNF, IL-6 and IL-10 serum levels were significantly lower in the treated group. Paw swelling and subcutaneous inflammation, evaluated clinically, were not different between CFA-induced groups. RC-3095 was able to improve experimental arthritis, attenuate joint damage and decrease serum levels of IFN-gamma, IL-1beta, TNF, IL-6 and IL-10. These data indicate that interference with GRP pathway is a potential new strategy for the treatment of RA that needs further investigational studies.


Effect of toxaphene on the performance of White Leghorn layers and their progeny.
An experiment involving 48 white leghorn layers fed 0, 10 and 100 p.p.m. of toxaphene has been conducted. Except for a slight decrease in egg production, no adverse effects on various performance parameters including fertility, hatchability and survival of progeny were observed. A significant increase (P less than .05) in average 7-day weights of progeny was noted.


Transient drought during flowering modifies the grain proteome of bread winter wheat.
Drought is among the most limiting factors for sustainable agricultural production. Water shortage at the onset of flowering severely affects the quality and quantity of grain yield of bread wheat (Triticum aestivum). Herein, we measured oxidative stress and photosynthesis-related parameters upon applying transient drought on contrasting wheat cultivars at the flowering stage of ontogenesis. The sensitive cultivar (Darunok Podillia) showed ineffective water management and a more severe decline in photosynthesis. Apparently, the tolerant genotype (Odeska 267) used photorespiration to dissipate excessive light energy. The tolerant cultivar sooner induced superoxide dismutase and showed less inhibited photosynthesis. Such a protective effect resulted in less affected yield and spectrum of seed proteome. The tolerant cultivar had a more stable gluten profile, which defines bread-making quality, upon drought. Water deficit caused the accumulation of medically relevant proteins: (i) components of gluten in the sensitive cultivar and (ii) metabolic proteins in the tolerant cultivar. We propose specific proteins for further exploration as potential markers of drought tolerance for guiding efficient breeding: thaumatin-like protein, 14-3-3 protein, peroxiredoxins, peroxidase, FBD domain protein, and Ap2/ERF plus B3 domain protein.


New horizons for GAG therapy in the management of urothelial damage.
Urothelial defects may manifest as various types of signs of symptoms such as frequency and urgency, haematuria and pain. Both prevention and treatment of urothelial damage is fundamental. Many currently adopted treatments lack robust clinical data and are associated with variability in management strategies. Glycosoaminoglycan (GAG) therapy is one of the most promising therapies in treatment of chemotherapy and radiotherapy-induced urothelium defects, and has been investigated in both animal models and clinical studies.


Infection therapy: the problem of drug resistance - and possible solutions.
The rising antibiotic resistance in major bacterial pathogens together with the breakdown of the antibiotic discovery platform creates a critical situation for infection therapy. Recent developments reviving new antibiotic discovery from defining chemical rules for membrane-passing compounds to isolation chips for soil bacteria and exploring the human microbiome for antibiotic-producing bacteria are discussed. The potential of bacteriocins, tailocins, phage lysins, phages, probiotics and commensal blends as alternatives to antibiotics is evaluated.


Carcinoid tumour of the oesophagus: report of a case.
A case of carcinoid tumour of the oesophagus in a 54-year-old man is described and the literature is briefly reviewed. This is the third reported case in the world literature and the rarity of the disease is emphasised.


Development of a laser heterodyne spectroradiometer for high-resolution measurements of CO2, CH4, H2O and O2 in the atmospheric column.
We have developed a portable near-infrared laser heterodyne radiometer (LHR) for quasi-simultaneous measurements of atmospheric carbon dioxide (CO2), methane (CH4), water vapor (H2O) and oxygen (O2) column absorption by using three distributed-feedback diode lasers as the local oscillators of the heterodyne detection. The developed system shows good performance in terms of its high spectral resolution of 0.066 cm-1 and a low solar power detection noise which was about 2 times the theoretical quantum limit. Its measurement precision of the column-averaged mole fraction for CO2 and CH4 is within 1.1%, based on the standard deviation from the mean value of the retrieved results for a clean sky. The column abundance information of the O2 is used to correct for the variations and uncertainties of atmosphere pressure, the solar altitude angle, and the prior profiles of pressure and temperature. Comparison measurements of daily column-averaged atmospheric mole fractions of CO2, CH4 and H2O, between our developed LHR and a greenhouse gas observing satellite, show a good agreement, which proves the reliability of our developed system.


Quantum solvation of phthalocyanine in superfluid helium droplets.
We have measured quantum states of the solvent-solute system of phthalocyanine in superfluid helium droplets in a high resolution pump-probe experiment. This provides evidence for the attribution of a splitting effect in the emission spectra of phthalocyanine in helium droplets to the relaxation of the first helium layer upon electronic excitation, measured recently by us. Our experimental results are a strong indication for the first helium layer playing a key roll for the solvation of molecules in helium droplets and, thus, for their spectroscopic features.


Outcomes in Child Health: Exploring the Use of Social Media to Engage Parents in Patient-Centered Outcomes Research.
With the rapid growth of technology and its improved accessibility globally, social media is gaining an increasingly important role in health care. Patients are frequently engaging with social media to access information, share content, and interact with others in online health communities. However, the use of social media as a stakeholder engagement strategy has been minimally explored, and effective methods for involving participants in research on the identification of patient-centered outcomes remain unknown. The aim of this study was to evaluate the process of using social media to engage parents in identifying patient-centered outcomes, using acute respiratory infections in children as an example to gauge feasibility. We conducted a process evaluation of a two-phase Web-based strategy to engage parents in research on patient-centered outcomes. In the first phase, we developed a website and study-specific Facebook and Twitter accounts to recruit parents to complete a Web-based survey identifying patient-centered outcomes. In the second phase, we used Facebook to host discussion with parents based on the survey results. The reach of social media as an engagement strategy and the characteristics of the population recruited were assessed. During the first phase, there were 5027 visits to the survey site, 110 participants completed the survey, 553 unique users visited the study website (675 visits), the Facebook page received 104 likes, and the Twitter account gained 52 followers over the 14-week study period. Most survey respondents identified Facebook (51.8%, 57/110) or a friend (45.5%, 50/110) as their source of referral. It was found that 70.0% (77/110) of respondents resided in Canada, in urban centers (92.7%, 102/110), and 88.2% (97/110) had a college or university degree or higher. The median year of birth was 1978 and 90.0% (99/110) were female. Most survey responses (88.2%, 97/110) were completed during the first month of the study. In the second phase, 4 parents participated in the discussion, our Facebook page gained 43 followers, and our posts reached 5866 users. Mirroring the first phase, most followers were female (79%, 34/43), between 35 and 44 years (49%, 21/43), and resided in Canada (98%, 42/43). User engagement was variable, with no clear patterns emerging in timing, topic, or type of post. Most participants were highly educated, urban dwelling, and female, limiting diversity and representativeness. The source of referral for most survey respondents was through Facebook or a friend, suggesting the importance of personal connections in the dissemination and uptake of information. User engagement with the Facebook-based discussion threads was inconsistent and difficult to initiate. Although there is substantial interest in the use of social media as a component of an effective patient engagement strategy, challenges regarding participant engagement, representativeness, obtaining buy-in, and resources required must be carefully considered.


Cloning and recombinant expression of a crustin-like gene from Chinese shrimp, Fenneropenaeus chinensis.
Antimicrobial peptides or proteins (AMPs) are proved to be one of the most important humoral factors to resist pathogen infection. As an antimicrobial protein, crustin had been described in invertebrates as a component of the innate immune system. A crustin-like gene (CruFc) was cloned from haemocytes of Chinese shrimp Fenneropenaeus chinensis by 3' and 5'-RACE PCR. The full-length cDNA consists of 523 with 405 bp open reading frame encoding 134 amino acids and the deduced peptide contains a putative signal peptide of 17 amino acids. The sequence also contains a whey-acidic protein (WAP) domain at the C-terminal. Transcripts of CruFc were mainly detected in haemocytes and gill by RT-PCR analysis. In addition, another full-length cDNA named CshFc was also cloned from haemocytes of Chinese shrimp and its inferred amino acid sequence lacks the WAP-type 'four-disulfide core' domain. The fusion proteins containing CruFc and CshFc were, respectively, produced and the antimicrobial assays revealed that the recombinant CruFc could inhibit the growth of gram-positive bacteria in vitro but the recombinant CshFc could not inhibit at the same conditions. The difference of antimicrobial activity between recombinant CruFc and CshFc provides the evidence that the four-disulfide core domain of crustin may play an important role in its biological function.


Tarsal tunnel syndrome caused by a talocalcaneal joint amyloidoma in a long-term haemodialysis patient: a case report.
We present a case of tarsal tunnel syndrome caused by an amyloidoma arising from the talocalcaneal joint in a 64-year-old man with a long history of haemodialysis. He presented with numbness in the medial plantar area of the right foot without any antecedent trauma. The numbness was minimal at rest but gradually worsened, causing difficulty, when walking. Paraesthesia was present on the medial sole of the right foot. A positive Tinel-like sign was noted 2.5 cm below the medial malleolus. Magnetic resonance imaging demonstrated a round lesion, 1 cm in diameter, in the calcaneus, which was hypointense on T1-weighted images and hyperintense on T2-weighted images. In addition, a mass, 1 cm in diameter with a signal isointense to that of muscle was found adjacent to the talocalcaneal joint. The medial plantar nerve was decompressed after removing a solid, 1-cm diameter mass from the talocalcaneal joint. At 6 months post surgery, the numbness had completely resolved. No recurrence was observed at the 24-month follow-up.


Clinical relevance of laboratory-reported antibiotic resistance in acute uncomplicated urinary tract infection in primary care.
To determine whether patients with an uncomplicated community-acquired urinary tract infection (UTI) and an isolate resistant to trimethoprim had worse clinical outcomes following empirical treatment with trimethoprim 200 mg twice daily for 3 days than did those with a susceptible isolate. This was a prospective cohort study of clinical outcome. We enrolled 497 women (>or=18-70 years) presenting to general practitioner surgeries in Norwich and Gloucester with at least two symptoms of acute (<7 days) uncomplicated UTI. Significant bacteriuria was defined as >or=10(4) cfu/mL from a mid-stream urine (MSU). Of enrolled patients 75% (334/448) had significant bacteriuria, and trimethoprim resistance was present in 13.9% (44/317) of isolates. Patients with resistant isolates had a longer median time to symptom resolution (7 versus 4 days, P=0.0002), greater reconsultation to the practice (39% versus 6% in first week, P<0.0001), more subsequent antibiotics (36% versus 4% in first week, P<0.0001) and higher rates of significant bacteriuria at 1 month (42% versus 20% with susceptible isolate, P=0.04). Half of patients reconsulting in the first week had a resistant organism. Patients with uncomplicated UTI caused by trimethoprim-resistant organisms had significantly worse clinical outcomes than those with trimethoprim-susceptible organisms. Nevertheless, trimethoprim resistance was rarer than predicted from routine laboratory submissions and we calculate that 23 women require microbiological investigation to prevent one reconsultation arising from resistance-based treatment failure. We therefore suggest empirical antibiotic treatment in acute, uncomplicated UTIs. If patients reconsult in the first week, we suggest a change of antibiotic treatment with urine culture and susceptibility testing then done. More generally, laboratory resources should concentrate on resistance surveillance to inform empirical antibiotic choice.


A hemi-metallocene chromium catalyst with trimethylaluminum-free methylaluminoxane for the synthesis of disentangled ultra-high molecular weight polyethylene.
Recently, it has been shown that by using a single-site catalytic system having titanium as a metallic center, it is possible to tailor the entanglement density in the amorphous region of a semi-crystalline ultra-high molecular weight polyethylene (UHMWPE). This route provides the possibility to make high-modulus, high-strength uniaxially and biaxially drawn tapes and films, without using any solvent during processing. In this publication, it is shown that a single-site catalyst having chromium as metallic center, proposed by Enders and co-workers, can also be tuned to provide control on the entanglement density during synthesis of the UHMWPE. However, to achieve the goal some modifications during the synthesis are required. The synthesized polymers can be processed in the solid state below the equilibrium melting temperature, resulting in uniaxially drawn tapes having tensile strength and modulus greater than 3.5 N/tex and 200 N/tex, respectively. Rheological studies have been performed to follow the increase in entanglement density in melt state with time.


Meta-eQTL: a tool set for flexible eQTL meta-analysis.
Increasing number of eQTL (Expression Quantitative Trait Loci) datasets facilitate genetics and systems biology research. Meta-analysis tools are in need to jointly analyze datasets of same or similar issue types to improve statistical power especially in trans-eQTL mapping. Meta-analysis framework is also necessary for ChrX eQTL discovery. We developed a novel tool, meta-eqtl, for fast eQTL meta-analysis of arbitrary sample size and arbitrary number of datasets. Further, this tool accommodates versatile modeling, eg. non-parametric model and mixed effect models. In addition, meta-eqtl readily handles calculation of chrX eQTLs. We demonstrated and validated meta-eqtl as fast and comprehensive tool to meta-analyze multiple datasets and ChrX eQTL discovery. Meta-eqtl is a set of command line utilities written in R, with some computationally intensive parts written in C. The software runs on Linux platforms and is designed to intelligently adapt to high performance computing (HPC) cluster. We applied the novel tool to liver and adipose tissue data, and revealed eSNPs underlying diabetes GWAS loci.


The use of ultrasound for the placement of dialysis catheters.
The jugular vein should be preferred to the subclavian vein for the placement of dialysis catheters, since subclavian catheters result in a high incidence (up to 50%) of subclavian vein thromboses and stenoses. We conducted a prospective, randomized study between July 1996 and March 1997 to find out whether through the use of ultrasound, the rate of unsuccessful attempts in puncturing the internal jugular vein could be reduced. Seventy-three internal jugular vein cannulations were performed on 65 patients, using the guide-wire technique (according to Seldinger). Two groups were formed randomly by lot: in the first group the position of the internal jugular vein was marked on the skin by the use of ultrasound (Picker CS9100, Convex 3.5 MHz) before disinfection and local anaesthesia took place. The puncture was performed according to this mark. In the second group, the internal jugular vein was cannulated with real-time ultrasound guidance on the monitor. Any withdrawal of the needle with a consecutive forward movement was judged as an unsuccessful attempt, whether or not a second skin puncture was performed. Thirty-seven punctures of the internal jugular vein with a skin mark determined by ultrasound yielded 87 unsuccessful attempts. Thirty-six punctures with real-time ultrasound guidance resulted in 10 unsuccessful attempts (P<0.01). The time from the beginning of the local anaesthesia to successful puncture was 4.8+/-2.2 min in the first group compared to 3.4+/-0.9 min in the second group (P<0.01). The cross-section of the internal jugular vein in the first group was 1.7+/-0.8 cm2 versus 1.5+/-0.8 cm2 in the second group (not significant). Neither of the two methods caused any complications. The puncture of the internal jugular vein with real-time ultrasound guidance resulted in significantly fewer unsuccessful attempts of venepuncture without requiring additional time.


[Unexpected risks during labour and delivery following a low risk pregnancy (author's transl)].
Of the maternity patient of the Munich perinatal study from 1975-1977 54.4% were considered to be low risk at the end of the pregnancy. Of these every third patient (17%) developed at least one risk during labour and delivery. These were considered to be consequence risks if they and been present at the onset of labour and delivery or progress risks if they developed during labour and delivery. The progress risks were defined as unpredictable and occurred in 4.7% of the total study. In this group the incidence of spontaneous delivery was only 36.0% compared with 88.5% in the compare group. The perinatal mortality of 6.9% was three times higher than for women who remained low risk during labour and delivery. The commonest unpredictable risks are anomalies of presentation. Acidosis and pyrexia during labour and delivery and emergency risks occur most often in women who start labour and delivery with existing risks. For these so-called progress risks with a high incidence of operative deliveries an operating room must be available at all times in the interest of mother and fetus. The monitoring of the fetus must also be available. Even following a low risk pregnancy monitoring and operation may become necessary.


[Influence of different designs and porcelain/glaze firing on the marginal and internal fit of implant-supported zirconia crowns].
This study investigated the influence of different designs and porcelain/glaze firing on the marginal and internal fit of three kinds of computer aided design/computer aided manufacturing (CAD/CAM) zirconia ceramic implant-supported crowns. Three groups of zirconia ceramic implant-supported crowns with different designs were produced from copings by using a Cercon CAD/CAM system (n = 8). The first two groups comprised double-layer crowns (zirconia coping + veneer) with regular (Group A) and full circumferential zirconia-collar marginal designs (Group B). The third group was composed of anatomic single-layer zirconia crowns without cores (Group C). Initially, the marginal and internal gaps of the copings and crowns were individually replicated by light-body silicon and then measured by micro-computed tomography scanning before and after porcelain/glaze firing. Five measurements were employed: vertical marginal gap (MG); horizontal marginal discrepancy (HMD); chamfer area (CA); axial wall (AW); and axial-occlusal transition area (AOT). Statistical analyses were performed by SPSS 17.0. HMD measurements in Group A were statistically higher than those in Groups B and C (P < 0.05), regardless of whether the values were obtained before or after porcelain/glaze firing. By contrast, the HIMD measurements in Groups B and C showed no significant difference (P > 0.05). Moreover, no differences were noted in MG, CA, AW, and AOT among the three groups (P > 0.05). All the measurements in the three groups showed no significant change after porcelain/glaze firing (P > 0.05), except for MG in Group A, which significantly decreased (P < 0.05). The marginal fits of the double-layer crowns with full circumferential zirconia-collar and the anatomic single-layer zirconia crowns were superior to that of the double-layer crowns with regular margins. The MG of the crowns with regular margins was obviously influenced by porcelain firing.


Does TLIF aggravate adjacent segmental degeneration more adversely than ALIF? A finite element study.
To determine whether transforaminal lumbar interbody fusion aggravate adjacent segmental degeneration more adversely than anterior lumbar interbody fusion. A normal finite element model, an anterior lumbar interbody fusion model and a transforaminal lumbar interbody fusion model of L3-5 were developed. 800 N compressive loading plus 10 Nm moments simulating flexion, extension, lateral bending and axial rotation were imposed on L3 superior endplate. The intradiscal pressure, intersegmental rotation and tresca stress in L3-4 were investigated. Under all loading directions, the values of three parameters in transforaminal lumbar interbody fusion model were the highest and those in normal model were the lowest, and the values in the ALIF model were higher than the normal model while lower than the TLIF model. In the ALIF and normal models, the values of the three parameters on left lateral bending and axial rotation were equal to those on right lateral bending and axial rotation. However, in the TILF model, the values on right lateral bending and axial rotation were larger than those on left lateral bending and axial rotation. Transforaminal lumbar interbody fusion aggravates adjacent segmental degeneration more adversely than anterior lumbar interbody fusion.


Basic concepts of functional arteriovenous MR imaging malformations.
This article reviews the technical features of functional MR imaging. Examples are presented demonstrating how MR imaging may be used to identify primary cortical regions adjacent to AVMs. Preliminary results suggest that cortical functions may undergo translocation when the AVM involves eloquent cortex. This finding underscores the importance of cortical mapping prior to surgical excision.


Far-from-equilibrium bidirectional transport system with constrained entrances competing for pool of limited resources.
Motivated by the wide occurrence of limited resources in many real-life systems, we investigate two-lane totally asymmetric simple exclusion process with constrained entrances under finite supply of particles. We analyze the system within the framework of mean-field theory and examine various complex phenomena, including phase separation, phase transition, and symmetry breaking. Based on the theoretical analysis, we analytically derive the phase boundaries for various symmetric as well as asymmetric phases. It has been observed that the symmetry-breaking phenomenon initiates even for very small number of particles in the system. The phases with broken symmetry originates as shock-low density phase under limited resources, which is in contrast to the scenario with infinite number of particles. As expected, the symmetry breaking continues to persist even for higher values of system particles. Seven stationary phases are observed, with three of them exhibiting symmetry-breaking phenomena. The critical values of a total number of system particles, beyond which various symmetrical and asymmetrical phases appear and disappear are identified. Theoretical outcomes are supported by extensive Monte Carlo simulations. Finally, the size-scaling effect and symmetry-breaking phenomenon on the simulation results have also been examined based on particle density histograms.


Copycat Suicides Without an Intention to Die After Watching TV Programs: Two Cases at Five Years of Age.
Suicide is an intentional self-destructive act. As conceptualization of death as an irreversible end occurs at approximately 8-10 years, attempted and completed suicides are rare before 7 years of age. Studies have suggested that media may contribute to increased suicides in adolescents through social learning. Effects of media on suicides were thoroughly evaluated in children and adolescents who committed suicide after identifying with the subject of a TV program, movie, or book. We present 2 cases at 5 years of age who committed suicide by hanging themselves after watching a TV program. These cases differed from copycat suicides reported in the literature that are performed mostly by adolescents because victims are very young children and because they died without an actual intent to die while they were imitating suicides. By presenting these cases, we want to emphasize that destructive effects of media may involve not only adults and adolescents but also very young children who do not have a completely developed concept of death.


[Recurrent disseminated intravascular coagulation in the course of gastrointestinal stromal tumor (GIST)].
The objective of this paper was the description of a case of 68-year old male patient with epithelioid gastrointestinal stromal tumor (GIST). Disseminated intravascular coagulation syndrome (DIC) as the first and predominant revealed symptom of disease was observed. The final diagnosis was performed using the specific immunohistochemic and ultrastructural assays. The diagnostic and therapeutic difficulties were presented in discussion.


The effect of alkaline pretreatment methods on cellulose structure and accessibility.
The effects of different alkaline pretreatments on cellulose structural features and accessibility are compared and correlated with the enzymatic hydrolysis of Populus. The pretreatments are shown to modify polysaccharides and lignin content to enhance the accessibility for cellulase enzymes. The highest increase in the cellulose accessibility was observed in dilute sodium hydroxide, followed by methods using ammonia soaking and lime (Ca(OH)2 ). The biggest increase of cellulose accessibility occurs during the first 10 min of pretreatment, with further increases at a slower rate as severity increases. Low temperature ammonia soaking at longer residence times dissolved a major portion of hemicellulose and exhibited higher cellulose accessibility than high temperature soaking. Moreover, the most significant reduction of degree of polymerization (DP) occurred for dilute sodium hydroxide (NaOH) and ammonia pretreated Populus samples. The study thus identifies important cellulose structural features and relevant parameters related to biomass recalcitrance.


An Adaptive Association Test for Multiple Phenotypes with GWAS Summary Statistics.
We study the problem of testing for single marker-multiple phenotype associations based on genome-wide association study (GWAS) summary statistics without access to individual-level genotype and phenotype data. For most published GWASs, because obtaining summary data is substantially easier than accessing individual-level phenotype and genotype data, while often multiple correlated traits have been collected, the problem studied here has become increasingly important. We propose a powerful adaptive test and compare its performance with some existing tests. We illustrate its applications to analyses of a meta-analyzed GWAS dataset with three blood lipid traits and another with sex-stratified anthropometric traits, and further demonstrate its potential power gain over some existing methods through realistic simulation studies. We start from the situation with only one set of (possibly meta-analyzed) genome-wide summary statistics, then extend the method to meta-analysis of multiple sets of genome-wide summary statistics, each from one GWAS. We expect the proposed test to be useful in practice as more powerful than or complementary to existing methods.


Multivisceral resections for rectal cancers: short-term oncological and clinical outcomes from a tertiary-care center in India.
Locally advanced rectal cancers (LARCs) involve one or more of the adjacent organs in upto 10-20% patients. The cause of the adhesions may be inflammatory or neoplastic, and the exact causes cannot be determined pre- or intra-operatively. To achieve complete resection, partial or total mesorectal excision (TME) en bloc with the involved organs is essential. The primary objective of this study is to determine short-term oncological and clinical outcomes in these patients undergoing multivisceral resections (MVRs). This is a retrospective review of a prospectively maintained database. Between 1 July 2013 and 31 May 2015, all patients undergoing MVRs for adenocarcinoma of the rectum were identified from this database. All patients who had en bloc resection of an adjacent organ or part of an adjacent organ were included. Those with unresectable metastatic disease after neoadjuvant therapy were excluded. Fifty-four patients were included in the study. Median age of the patients was 43 years. Mucinous histology was detected in 29.6% patients, and signet ring cell adenocarcinoma was found in 24.1% patients. Neoadjuvant therapy was given in 83.4% patients. R0 resection was achieved in 87% patients. Five-year overall survival (OS) was 70% for the entire cohort of population. In Indian subcontinent, MVRs in young patients with high proportion of signet ring cell adenocarcinomas based on magnetic resonance imaging (MRI) of response assessment (MRI 2) is associated with similar circumferential resection margin (CRM) involvement and similar adjacent organ involvement as the western patients who are older and surgery is being planned on MRI 1 (baseline pelvis). However, longer follow-up is needed to confirm noninferiority of oncological outcomes.


Identification of a novel neuronal C-SRC exon expressed in human brain.
Neuronal cells are known to express at least two different forms of the C-SRC proto-oncogene as a consequence of alternative splicing events which add an 18-nucleotide exon (the NI exon) between C-SRC exons 3 and 4. Here we report that a second neuronal exon of C-SRC is also present between C-SRC exons 3 and 4. This neuronal exon (the NII exon) of C-SRC was isolated from human adult and fetal brain-derived cDNAs and contains 33 nucleotides capable of encoding 11 amino acids (Gln-Thr-Trp-Phe-Thr-Phe-Arg-Trp-Leu-Gln-Arg). The human NI exon was located approximately 390 nucleotides from the end of C-SRC exon 3, whereas the NII exon was approximately 1,000 nucleotides from the beginning of C-SRC exon 4. Analysis of human brain RNA revealed that the NII exon is utilized primarily in conjunction with the NI exon to yield transcripts capable of encoding C-SRC products possessing 17 additional amino acids. These splicing events, which occur between the NI and NII exons, are predicted to alter the sixth amino acid encoded by the NI exon from an arginine to a serine residue, producing a potentially novel phosphorylation site. Analysis of the different C-SRC RNA transcripts revealed that the level of C-SRC RNA containing both NI and NII exons is similar in adult and fetal brain tissue, whereas the level of C-SRC RNA containing only the NI exon or the nonneuronal form of C-SRC RNAs is significantly higher in fetal brain tissues. These results indicate that the expression and splicing pattern of the C-SRC gene are developmentally regulated in the human brain.


Xanol Promotes Apoptosis and Autophagy and Inhibits Necroptosis and Metastasis via the Inhibition of AKT Signaling in Human Oral Squamous Cell Carcinoma.
Angelica keiskei Koidzumi (A. keiskei) is used as a traditional medicine, anti-aging agent, and health food, as well as to restore vitality. Xanthoangelol (xanol), a prenylated chalcone, is the predominant constituent of A. keiskei. Oral squamous cell carcinoma (OSCC), the most common malignancy, has a high proliferation rate and frequent metastasis. However, it is unknown whether xanol has anti-OSCC effects on apoptosis, autophagy, and necroptosis. In the present study, we purified xanol from A. keiskei and demonstrated that it suppressed cell proliferation and induced cytotoxicity in human OSCC. Xanol triggered apoptotic cell death by regulating apoptotic machinery molecules but inhibited necroptotic cell death by dephosphorylating the necroptotic machinery molecules RIP1, RIP3, and MLKL in human OSCC. We also found that xanol inhibited the PI3K/AKT/mTOR/p70S6K pathway and induced autophagosome formation by enhancing beclin-1 and LC3 expression levels and reducing p62 expression levels. Furthermore, we showed that xanol prevented the metastatic phenotypes of human OSCC by inhibiting migration and invasion via the reduction of MMP13 and VEGF. Finally, we demonstrated that xanol exerted anticancer effects on tumorigenicity associated with its transformed properties. Taken together, these findings demonstrate the anticancer effects and biological mechanism of action of xanol as an effective phytomedicine for human OSCC.


Characteristics of veterans in community-based treatment programs for substance use disorders: an analysis of data from a state-wide system.
This study examined records of patients in New York State treatment programs for substance use disorders from 1995 to 2012, which consisted of 81,471 patients with a self-reported veteran status and 1,260,618 without. Results indicated that, compared to other patients in community-based treatment, veterans have distinctive demographic characteristics, primary substance use, and treatment participation. Implications of the findings were discussed. The authors call for more in-depth research to examine veterans' pathways into community-based treatment, their perception of and experience with treatment services, and the likely influence of cultural background and the role of specific military experiences on their treatment outcomes.


Mitral valve replacement in idiopathic eosinophilic endocarditis without peripheral eosinophilia.
Idiopathic hypereosinophilic syndrome (IHS) is a rare systemic disease than can cause multiple organ failure by eosinophilic infiltration. Cardiac involvement is characterized by endocardial fibrosis and overlying thrombus leading to restrictive cardiomyopathy and valvular dysfunction. The absence of peripheral eosinophilia does not exclude eosinophilic cardiac involvement. Surgical experience of patients with mitral dysfunction caused by this syndrome is limited and valvular replacement is most often performed. Mechanical valvular replacement has a high incidence of recurrent obstructive thrombosis and replacement by bioprosthesis is recommended despite associated restrictive cardiomyopathy. This report describes a patient who presented mitral insufficiency caused by eosinophilic endocarditis without peripheral eosinophilia who underwent mitral valve replacement.


Fish bone foreign bodies in the pharynx and upper esophagus: evaluation with 64-slice MDCT.
Fish bone (FB) is one of the common causes of foreign body impaction in the pharynx and esophagus. To investigate the efficacy of 64-slice multidetector computed tomography (MDCT) for the evaluation of pharynx and upper esophageal FB foreign bodies. Sixty-six patients with suspected FB foreign body ingestion were examined by plain radiography (n = 40) and unenhanced MDCT (n = 66). We analyzed the presence, location, size, shape, and lying position of the foreign bodies. On MDCT, 46 foreign bodies were detected. Among them, 45 were confirmed by endoscopy. The sensitivity of MDCT for the detection of foreign bodies was 100%, which was superior to that of the plain radiography (51.7%). The location of the foreign bodies was most common in the upper esophagus (n = 22, 47.8%), followed by pharyngoesophageal junction (n = 10, 21.7%), transjunctional (n = 7, 15.2%), hypopharynx (n = 5, 10.9%), and oropharynx (n = 2, 4.3%). Their longest length was 5.3-40.1 mm (mean, 21.3 mm). Thirty-three FBs (71.7%) were linear and 13 (28.3%) were flat in shape. They showed transverse (n = 23, 50.0%), parallel (n = 13, 28.3%), and oblique positions (n = 10, 21.7%) to the long axis of the pharynx and esophagus, respectively. MDCT is useful for the evaluation of the pharynx and upper esophageal FB foreign bodies.


Fluorescence Polarization Based Nucleic Acid Testing for Rapid and Cost-Effective Diagnosis of Infectious Disease.
A new nucleic acid detection method was developed for a rapid and cost-effective diagnosis of infectious disease. This approach relies on the three unique elements: 1) detection probes that regulate DNA polymerase activity in response to the complementary target DNA; 2) universal reporters conjugated with a single fluorophore; and 3) fluorescence polarization (FP) detection. As a proof-of-concept, the assay was used to detect and sub-type Salmonella bacteria with sensitivities down to a single bacterium in less than three hours.


Shaping Beam Profiles Using Plastic Optical Fiber Tapers with Application to Ice Sensors.
Using either bulk or fiber optics the profile of laser beams can be altered from Gaussian to top-hat or hollow beams allowing enhanced performance in applications like laser cooling, optical trapping, and fiber sensing. Here, we report a method based on multimode Plastic Optical Fibers (POF) long-tapers, to tweak the beam profile from near Gaussian to a hollow beam, by generating surface irregularities on the conical sections of the taper with a heat-and-pull technique. Furthermore, a cutback technique applied on long tapers expanded the output beam profile by more than twice the numerical aperture (NA) of the fiber. The enhanced sensitivity and detection efficiency of the extended profile was tested on a fiber optical ice sensor related to aviation safety.


Surface expression of TTYH2 is attenuated by direct interaction with β-COP.
TTYH2 is a calcium-activated, inwardly rectifying anion channel that has been shown to be related to renal cancer and colon cancer. Based on the topological prediction, TTYH2 protein has five transmembrane domains with the extracellular N-terminus and the cytoplasmic C-terminus. In the present study, we identified a vesicle transport protein, β-COP, as a novel specific binding partner of TTYH2 by yeast two-hybrid screening using a human brain cDNA library with the C-terminal region of TTYH2 (TTYH2-C) as a bait. Using in vitro and in vivo binding assays, we confirmed the protein-protein interactions between TTYH2 and β-COP. We also found that the surface expression and activity of TTYH2 were decreased by co-expression with β-COP in the heterologous expression system. In addition, β-COP associated with TTYH2 in a native condition at a human colon cancer cell line, LoVo cells. The over-expression of β-COP in the LoVo cells led to a dramatic decrease in the surface expression and activity of endogenous TTYH2. Collectively, these data suggested that β-COP plays a critical role in the trafficking of the TTYH2 channel to the plasma membrane. [BMB Reports 2019; 52(7): 445-450].


HLA specificities are associated with prognosis in IGHV-mutated CLL-like high-count monoclonal B cell lymphocytosis.
Molecular alterations leading progression of asymptomatic CLL-like high-count monoclonal B lymphocytosis (hiMBL) to chronic lymphocytic leukemia (CLL) remain poorly understood. Recently, genome-wide association studies have found 6p21.3, where the human leukocyte antigen (HLA) system is coded, to be a susceptibility risk region for CLL. Previous studies have produced discrepant results regarding the association between HLA and CLL development and outcome, but no studies have been performed on hiMBL. We evaluated the role of HLA class I (-A, -B and -C) and class II (-DRB1 and -DQB1) in hiMBL/CLL susceptibility, hiMBL progression to CLL, and treatment requirement in a large series of 263 patients diagnosed in our center with hiMBL (n = 156) or Binet A CLL (n = 107). No consistent association between HLA specificities and hiMBL or CLL susceptibility was found. With a median follow-up of 7.7 years, 48/156 hiMBLs (33%) evolved to asymptomatic CLLs, while 16 hiMBLs (10%) and 44 CLLs (41%) required treatment. No HLA specificities were found to be significantly associated with hiMBL progression or treatment in the whole cohort. However, within antigen-experienced immunoglobulin heavy-chain (IGHV)-mutated hiMBLs, which represents the highest proportion of hiMBL cases (81%), the presence of HLA-DQB1*03 showed a trend to a higher risk of progression to CLL (60% vs. 26%, P = 0.062). Moreover, HLA-DQB1*02 specificity was associated with a lesser requirement for 15-year treatment (10% vs. 36%, P = 0.012). In conclusion, our results suggest a role for HLA in IGHV-mutated hiMBL prognosis, and are consistent with the growing evidence of the influence of 6p21 on predisposition to CLL. Larger non-biased series are required to enable definitive conclusions to be drawn.


Understanding the cancer cell phenotype beyond the limitations of current omics analyses.
Efforts to understand the mechanistic principles driving cancer metabolism and proliferation have been lately governed by genomic, transcriptomic and proteomic studies. This paper analyzes the caveats of these approaches. As molecular biology's central dogma proposes a unidirectional flux of information from genes to mRNA to proteins, it has frequently been assumed that monitoring the changes in the gene sequences and in mRNA and protein contents is sufficient to explain complex cellular processes. Such a stance commonly disregards that post-translational modifications can alter the protein function/activity and also that regulatory mechanisms enter into action, to coordinate the protein activities of pathways/cellular processes, in order to keep the cellular homeostasis. Hence, the actual protein activities (as enzymes/transporters/receptors) and their regulatory mechanisms ultimately dictate the final outcomes of a pathway/cellular process. In this regard, it is here documented that the mRNA levels of many metabolic enzymes and transcriptional factors have no correlation with the respective protein contents and activities. The validity of current clinical mRNA-based tests and proposed metabolite biomarkers for cancer detection/prognosis is also discussed. Therefore, it is proposed that, to achieve a thorough understanding of the modifications undergone by proliferating cancer cells, it is mandatory to experimentally analyze the cellular processes at the functional level. This could be achieved (a) locally, by examining the actual protein activities in the cell and their kinetic properties (or at least kinetically characterize the most controlling steps of the pathway/cellular process); (b) systemically, by analyzing the main fluxes of the pathway/cellular process, and how they are modulated by metabolites, all which should contribute to comprehending the regulatory mechanisms that have been altered in cancer cells. By adopting a more holistic approach it may become possible to improve the design of therapeutic strategies that would target cancer cells more specifically.


A lexicon for hepatocellular carcinoma surveillance ultrasonography: benign versus malignant lesions.
To suggest a lexicon for liver ultrasonography and to identify radiologic features indicative of benign or malignant lesions on surveillance ultrasonography. This retrospective study included 188 nodules (benign, 101; malignant, 87) from 175 at-risk patients identified during surveillance ultrasonography for hepatocellular carcinoma. We created a lexicon for liver ultrasonography by reviewing relevant literature regarding the ultrasonographic features of hepatic lesions. Using this lexicon, two abdominal radiologists determined the presence or absence of each ultrasonographic feature for the included hepatic lesions. Independent factors associated with malignancy and interobserver agreement were determined by logistic regression analysis and kappa statistics, respectively. Larger tumor size (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.06-1.183; P<0.001), multinodular confluent morphology (OR, 7.712; 95% CI, 1.053-56.465; P=0.044), thick hypoechoic rim (OR, 5.878; 95% CI, 2.681-12.888; P<0.001), and posterior acoustic enhancement (OR, 3.077; 95% CI, 1.237-7.655; P=0.016) were independently associated with malignant lesions. In a subgroup analysis of lesions <2 cm, none of the ultrasonographic features were significantly associated with malignancy or benignity. Interobserver agreement for morphology was fair (κ=0.36), while those for rim (κ=0.427), echogenicity (κ=0.549), and posterior acoustic enhancement (κ=0.543) were moderate. For hepatic lesions larger than 2 cm, some ultrasonography (US) features might be suggestive of malignancy. We propose a lexicon that may be useful for surveillance US.


Reactive oxygen species-mediated mitochondrial pathway is involved in Baohuoside I-induced apoptosis in human non-small cell lung cancer.
Baohuoside I (also known as Icariside II) is a flavonoid isolated from Epimedium koreanum Nakai. Although Baohuoside I exhibits anti-inflammatory and anti-cancer activities, its molecular targets/pathways in human lung cancer cells are poorly understood. Therefore, in the present study, we investigated the usefulness of Baohuoside I as a potential apoptosis-inducing cytotoxic agent using human adenocarcinoma alveolar basal epithelial A549 cells as in vitro model. The apoptosis induced by Baohuoside I in A549 cells was confirmed by annexin V/propidium iodide double staining, cell cycle analysis and dUTP nick end labeling. Further research revealed that Baohuoside I accelerated apoptosis through the mitochondrial apoptotic pathway, involving the increment of BAX/Bcl-2 ratio, dissipation of mitochondrial membrane potential, transposition of cytochrome c, caspase 3 and caspase 9 activation, degradation of poly (ADP-ribose) polymerase and the over-production of reactive oxygen species (ROS). A pan-caspase inhibitor, Z-VAD-FMK, only partially prevented apoptosis induced by Baohuoside I, while NAC, a scavenger of ROS, diminished its effect more potently. In addition, the apoptotic effect of Baohuoside I was dependent on the activation of ROS downstream effectors, JNK and p38(MAPK), which could be almost abrogated by using inhibitors SB203580 (an inhibitor of p38(MAPK)) and SP600125 (an inhibitor of JNK). These findings suggested that Baohuoside I might exert its cytotoxic effect via the ROS/MAPK pathway.


S100A9‑containing serum exosomes obtained from patients with burn injuries promote myocardial cell pyroptosis through NLRP3.
S100 calcium-binding protein A9 (S100A9) is highly expressed in the serum exosomes of patients with burn injuries. The present study aimed to investigate the underlying mechanisms of burn injury-associated exosomes in the regulation of myocardial cell pyroptosis. Reverse transcription-quantitative PCR and western blotting were used to examine relative mRNA and protein levels. The morphology of exosomes was visualized using transmission electron microscopy. The expression levels of IL-1β and IL-18 in cells were examined using ELISA kits. Finally, cell pyroptosis was examined using flow cytometry. When AC16 cells were treated with the serum exosomes obtained from patients with burn injuries, pyroptosis was significantly promoted and the expression levels of IL-1β and IL-18 were increased. NLR family pyrin domain containing 3 (NLRP3), S100A9, caspase-1 and Gasdermin D (GSDMD)-N expression levels were also upregulated. However, these were significantly reversed by anti-S100A9 antibodies. Thereafter, CY-09, an NLRP3 inhibitor, was revealed to restore the increase in pyroptosis and IL-18, IL-1β, caspase-1, NLRP3 and GSDMD-N expression levels caused by recombinant S100A9 to be similar to the control. These findings suggested that burn injury-associated exosomes containing S100A9 can affect AC16 cell pyroptosis through NLRP3.


The lighthouse strategy: Improving the functional status of patients with unilateral neglect after stroke and brain injury using a visual imagery intervention.
This study extends the work of J. Niemeier (1998) by using visual imagery for amelioration of the devastating impact of visual inattention or neglect on recovery from stroke or other brain injuries. Ten individuals with unilateral visual neglect who were undergoing acute physical rehabilitation after brain injury were cued by their interdisciplinary treatment team members to "be like" horizon-illuminating lighthouses and turn their heads left and right during functional and therapy training tasks. These treatment group patients, in comparison with waiting list controls, performed significantly better and more safely on route finding (p <.001), walking or wheelchair (p <.05), and problem solving (p <.05) tasks. The use of visual imagery techniques in rehabilitation of brain injuries is discussed.


An incremental target-adapted strategy for active geometric calibration of projector-camera systems.
The calibration of a projector-camera system is an essential step toward accurate 3-D measurement and environment-aware data projection applications, such as augmented reality. In this paper we present a two-stage easy-to-deploy strategy for robust calibration of both intrinsic and extrinsic parameters of a projector. Two key components of the system are the automatic generation of projected light patterns and the incremental calibration process. Based on the incremental strategy, the calibration process first establishes a set of initial parameters, and then it upgrades these parameters incrementally using the projection and captured images of dynamically-generated calibration patterns. The scene-driven light patterns allow the system to adapt itself to the pose of the calibration target, such that the difficulty in feature detection is greatly lowered. The strategy forms a closed-loop system that performs self-correction as more and more observations become available. Compared to the conventional method, which requires a time-consuming process for the acquisition of dense pixel correspondences, the proposed method deploys a homography-based coordinate computation, allowing the calibration time to be dramatically reduced. The experimental results indicate that an improvement of 70% in reprojection errors is achievable and 95% of the calibration time can be saved.


Toscana virus genome stability: data from a meningoencephalitis case in Mantua, Italy.
In July of 2013, samples from a patient with a neurological syndrome were collected from Mantua hospital and sent to the National Reference Laboratory for Arboviruses (National Institute of Health, Rome). On the basis of the symptoms, serological and molecular assays were performed to diagnose either West Nile virus (WNV) or Toscana virus (TOSV) infection. Molecular and serological tests confirmed TOSV infection. Virus isolation was obtained from cerebrospinal fluid. A full genome sequence was determined from this TOSV strain with next-generation sequencing using Ion Torrent technology. Nucleotide and amino acidic sequences grouped phylogenetically with lineage TOSV A and showed a low genome variability.


A thermodynamic analysis of RNA transcript elongation and termination in Escherichia coli.
In the first part of this paper we present a thermodynamic analysis of the elongation phase of transcription in Escherichia coli. The stability of the elongation complex is described by a "free energy of formation" function (delta G zero f) that is a sum of terms for forming (i) a locally denatured 17-base-pair DNA "bubble"; (ii) a constant-length hybrid between the 3'-terminal 12-nucleotide residues of the RNA transcript and the corresponding region of the DNA template strand; and (iii) a set of binding interactions between the polymerase and certain DNA and RNA residues within and near the "transcription bubble". The transcriptional elongation complex is very stable at most positions along a natural DNA template and moves in a highly processive fashion. At these positions, the delta G zero f function provides a quantitative measure of the stability of the elongation complex. Besides allowing for the polymerization of the RNA transcript, the elongation complex also serves to define the context within which transcript termination occurs. In the second part of the paper the thermodynamic analysis is extended to discriminate between template positions at which the elongation complex is stable and positions at which it is rendered relatively unstable by the presence of a string of rU residues at the 3'-terminus of the RNA together with the formation of a specific RNA hairpin just upstream of this point. Most factor-independent (intrinsic) termination events are thermodynamically disallowed at the former positions and are thermodynamically allowed at the latter positions. The extended form of the analysis closely predicts the exact sites of termination at a number of intrinsic terminators (and attenuators) in the E. coli genome. It also correctly predicts bidirectional function for a number of bidirectional terminators. In some cases it may identify terminators that are similar to the intrinsic type but that require additional protein factors, unusual polymerase-nucleic acid interactions, or rate-limiting conformational changes in order to function. Finally, it successfully locates intrinsic terminators within a number of E. coli operons and discriminates between these terminators and the surrounding DNA sequence.


Haber's syndrome.
Haber's syndrome is a rare genodermatosis characterised by an early onset rosacea-like eruption associated with multiple truncal keratotic lesions. The present study reports the clinical presentation, histology and response to therapy of two cases of Haber's syndrome. The cases presented with the typical features of Haber's syndrome. Case 1 also had diffuse palmoplantar keratoderma and prominent nail cuticles, and case 2 had diffuse palmar keratoderma. These features have not been previously reported in Haber's syndrome. In the present study Haber's syndrome is reviewed, and its relationship to Dowling-Degos disease and acropigmentation of Kitamura are discussed.


Small-Sized mPEG-PLGA Nanoparticles of Schisantherin A with Sustained Release for Enhanced Brain Uptake and Anti-Parkinsonian Activity.
Schisantherin A (SA) is a promising anti-Parkinsonism natural product. However, its poor water solubility and rapid serum clearance impose significant barriers to delivery of SA to the brain. This work aimed to develop SA in a nanoparticle formulation that extended SA circulation in the bloodstream and consequently an increased brain uptake and thus to be potentially efficacious for the treatment of Parkinson's disease (PD). Spherical SA nanoparticles with a mean particle size of 70 nm were prepared by encapsulating SA into methoxy poly(ethylene glycol)-block-poly(d,l)-lactic-co-glycolic acid (mPEG-PLGA) nanoparticles (SA-NPs) with an encapsulation efficiency of ∼91% and drug loading of ∼28%. The in vitro release of the SA-NPs lasted for 48 h with a sustained-release pattern. Using the Madin-Darby canine kidney (MDCK) cell model, the results showed that first intact nanoparticles carrying hydrophobic dyes were internalized into cells, then the dyes were slowly released within the cells, and last both nanoparticles and free dyes were externalized to the basolateral side of the cell monolayer. Fluorescence resonance energy transfer (FRET) imaging in zebrafish suggested that nanoparticles were gradually dissociated in vivo with time, and nanoparticles maintained intact in the intestine and brain at 2 h post-treatment. When SA-NPs were orally administrated to rats, much higher Cmax and AUC0-t were observed in the plasma than those of the SA suspension. Furthermore, brain delivery of SA was much more effective with SA-NPs than with SA suspension. In addition, the SA-NPs exerted strong neuroprotective effects in zebrafish and cell culture models of PD. The protective effect was partially mediated by the activation of the protein kinase B (Akt)/glycogen synthase kinase-3β (Gsk3β) pathway. In summary, this study provides evidence that small-sized mPEG-PLGA nanoparticles may improve cross-barrier transportation, oral bioavailability, brain uptake, and bioactivity of this Biopharmaceutics Classification System (BCS) Class II compound, SA.


Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells.
Recombinant Adeno-Associated Virus (rAAV) is considered as one of the most successful and widely used viral vectors for in vivo gene therapy. However, host immune responses to the vector and/or the transgene product remain a major hurdle to successful AAV gene transfer. In contrast to antivector adaptive immunity, the initiation of the innate immunity towards rAAV is still poorly understood but is directly dependent on the interaction between the viral vector and innate immune cells. Here, we used a quantitative transcriptomic-based approach to determine the activation of inflammatory and anti-viral pathways after rAAV8-based infection of monocyte-derived dendritic cells (moDCs) obtained from 12 healthy human donors. We have shown that rAAV8 particles are efficiently internalized, but that this uptake does not induce any detectable transcriptomic change in moDCs in contrast to an adenoviral infection, which upregulates anti-viral pathways. These findings suggest an immunologically favorable profile for rAAV8 serotype with regard to in vitro activation of moDC model. Transcriptomic analysis of rAAV-infected innate immune cells is a powerful method to determine the ability of the viral vector to be seen by these sensor cells, which remains of great importance to better understand the immunogenicity of rAAV vectors and to design immune-stealth products.


High resolution computed tomography in evaluation of the temporal bone.
High resolution computed tomography has completely replaced conventional multidirectional tomography in the evaluation of the temporal bone. Unprecedented detail is now available for evaluation of both middle ear and inner ear structures. A sampling of our experience in the evaluation of tubotympanic disease, otosclerosis, trauma, neoplastic disease, and congenital abnormalities is included in this publication. The state of the art in evaluation of sensorineural hearing loss is also illustrated.


[Inhalation injury in burn patients].
The clinical course of inhalation injury is variable. The routine use of fiberoptic bronchoscopy provides an accurate and safe diagnosis; by this examination it is possible to recognize alterations down to the terminal airway. Biopsies of tracheobronchial mucosa can ensure the diagnosis. By means of fiberoptic examination and blood gases it is possible to realize a differentiation of inhalation injury. According to the analysis of our patients an inhalation injury was found in 20.1%. The mortality rate due to the inhalation injury amounts to 14.4%.


Electrical conduction in canine pulmonary veins: electrophysiological and anatomic correlation.
Paroxysmal atrial fibrillation in patients is often initiated by foci in the pulmonary veins. The mechanism of these initiating arrhythmias is unknown. The aim of this study was to determine electrophysiological characteristics of canine pulmonary veins that may predispose to initiating arrhythmias. Extracellular recordings were obtained from the luminal side of 9 pulmonary veins in 6 Langendorff-perfused dog hearts after the veins were incised from the severed end to the ostium. Pulmonary veins were paced at the distal end, the ostium, and an intermediate site. During basic and premature stimulation, extracellular electrical activity was recorded with a grid electrode that harbored 247 electrode terminals. In 4 hearts, intracellular electrograms were recorded with microelectrodes. Myocyte arrangement immediately beneath the venous walls was determined by histological analysis in 3 hearts. Extracellular mapping revealed slow and complex conduction in all pulmonary veins. Activation delay after premature stimulation could be as long as 96 ms over a distance of 3 mm. Action potential duration was shorter at the distal end of the veins than at the orifice. No evidence for automaticity or triggered activity was found. Histological investigation revealed complex arrangements of myocardial fibers that often showed abrupt changes in fiber direction and short fibers arranged in mixed direction. Zones of activation delay were observed in canine pulmonary veins and correlated with abrupt changes in fascicle orientation. This architecture of muscular sleeves in the pulmonary veins may facilitate reentry and arrhythmias associated with ectopic activity.


ATP-dependent transport of organic anions in secretory vesicles of Saccharomyces cerevisiae.
Secretory mutants (sec1, sec6) of Saccharomyces cerevisiae accumulate large pools of secretory vesicles at the restrictive temperature (37 degrees C) because of a block in the delivery of vesicles to the cell surface. We report that secretory vesicles isolated from sec mutants exhibit ATP-dependent uptake of two classes of organic anions that are substrates for the canalicular carriers of mammalian liver. Transport of the bile acid taurocholate (TC) and the glutathione conjugate of 1-chloro-2,4-dinitrobenzene (GS-DNP) into vesicles was temperature dependent and saturable and required ATP and Mg2+. Estimates of Km and Vmax were 177 microM and 1.2 nmol.min-1.mg-1 and 262 microM and 0.53 nmol.min-1.mg-1 for TC and GS-DNP, respectively. TC and GS-DNP did not complete for transport. TC transport was sensitive to vanadate and 4,4'-diisothiocyanostilbene-2,2'-disulfonate, inhibited by glycocholate, and retained partial activity when UTP and GTP, but not nonhydrolyzable ATP analogues, replaced ATP. Dissipation of the electrochemical potential with a nitrate buffer and ionophores partially decreased (30-40%) the transport of both anions. Direct testing of the influence of membrane potential was performed in sec6-4 mutants, in which the expression of electrogenic [H+]ATPase activity is reduced by > 85% in glucose-containing medium. Vesicles from sec6-4 retained full activity for ATP-dependent TC and GS-DNP transport. These results indicate that the transporters operate independently of the membrane potential and that ATP is required. These findings reveal that yeast possess separate ATP-dependent transport mechanisms for elimination of bile acids and glutathione conjugates. The mechanisms are functionally similar to those present in mammalian systems.


Growth factor messenger ribonucleic acid expression during differentiation of porcine embryonic myogenic cells.
The growth factors, IGF-I and II, their binding proteins, IGFBP, and members of the transforming growth factor (TGF) superfamily (myostatin and TGFbeta1) are known to regulate proliferation and differentiation of myogenic cells. We hypothesized that changes in the relative expression of members of the IGF and TGFbeta systems play a significant role in regulating myogenesis in porcine embryonic myogenic cell (PEMC) cultures. Therefore, determining the expression patterns of these factors during PEMC myogenesis is important. Consequently, we used real-time PCR to explore the pattern of IGF-I; IGF-II; IGFBP-2, -3, and -5; IGF-type-I receptor; myogenin; myostatin; and TGFbeta1 mRNA expression during PEMC myogenesis. The progression of differentiation was assessed using creatine kinase activity and myogenin mRNA expression. As anticipated, creatine kinase activity was low in PEMC cultures at 48 h and increased 20-fold (P < 0.0001) between 48 h and its peak at 144 h. Similarly, myogenin mRNA was low at 48 h and increased approximately 5-fold (P < 0.0001) as differentiation progressed, peaking at 120 h and decreasing at 144 h. The patterns of IGF-I and IGFBP-2 mRNA expression were similar and were relatively lower in 48-h PEMC cultures, increasing approximately 5-fold (P < 0.0001) to their greatest levels at 120 h. In contrast, IGF-II and IGFBP-5 mRNA levels were relatively high at 48 h, peaking at 72 h, and steadily decreasing by 60 and 80%, respectively (P < 0.001), at 144 h. The level of IGF-type-I receptor mRNA was relatively high until 96 h of culture, after which it decreased 40% (P < 0.01), reaching a low at 144 h. Levels of IGFBP-3 mRNA were relatively high at 48 h, dropped approximately 40% to their lowest level at 72 h (P < 0.001), and then increased approximately 60% (P < 0.001) to their greatest levels at 144 h. Levels of TGFbeta1 mRNA decreased approximately 30% (P < 0.0001) between 48 and 96 h, then quickly rebounded to a peak at 120 h, and by 144 h had dropped to the levels seen at 72 h. Myostatin mRNA was at its greatest level at 48 h and declined rapidly between 72 and 96 h, finally decreasing by approximately 80% at 144 h (P < 0.0001). Our data demonstrate that these factors are differentially regulated during PEMC myogenesis and provide new information about their pattern of mRNA expression in cultured porcine muscle cells.


Ontogenic changes in renal response to alpha 1-adrenoceptor stimulation in sheep.
The present study was designed to examine the effect of direct intrarenal infusion of the alpha 1-adrenoceptor agonist, phenylephrine, on urinary flow rate (UFR) and on renal Na and Cl excretion in conscious and chronically instrumented fetal (128-133 days gestation, term 145 days), newborn (6-12 days), and adult sheep. Five different renal concentrations of phenylephrine, varying from 5 +/- 1 to 72 +/- 2 ng/ml, were studied. Low renal phenylephrine concentration (< or = 12 +/- 1 ng/ml) induced a significant renal vasoconstrictor response in fetuses but not in newborn and adult sheep. The effects of intrarenal phenylephrine infusion on UFR and fractional excretion of Na (FENa) was greater (P < 0.05) in newborn lambs than in fetal and adult sheep. At a renal concentration of phenylephrine between 9 +/- 1 and 12 +/- 1 ng/ml, the percent decrease in UFR was greater (P < 0.05) in newborn lambs (-19.1 +/- 4.7%) than in fetal (9.8 +/- 8.9%) and adult sheep (-3.3 +/- 3.9). The percent decrease in FENa at renal concentration of phenylephrine between 18 +/- 1 and 24 +/- 1 ng/ml was also significantly (P < 0.05) larger in newborn lambs (-20.2 +/- 2.8%) than in fetal (-8.0 +/- 3.1%) and adult sheep (-11.2 +/- 2.6%). In summary, the present results indicate that the fetal kidney has a limited ability to increase sodium reabsorption in response to stimulation of alpha-adrenoceptors and that the effect of renal alpha-adrenoceptor stimulation on urinary volume and urinary sodium excretion increases during the newborn period.


Patterns of tobacco use and dual use in US young adults: the missing link between youth prevention and adult cessation.
Few studies address the developmental transition from youth tobacco use uptake to regular adulthood use, especially for noncigarette tobacco products. The current study uses online panel data from the Legacy Young Adult Cohort Study to describe the prevalence of cigarette, other tobacco product, and dual use in a nationally representative sample of young adults aged 18-34 (N = 4,201). Of the 23% of young adults who were current tobacco users, 30% reported dual use. Ever use, first product used, and current use were highest for cigarettes, cigars, little cigars, and hookah. Thirty-two percent of ever tobacco users reported tobacco product initiation after the age of 18 and 39% of regular users reported progressing to regular use during young adulthood. This study highlights the need for improved monitoring of polytobacco use across the life course and developing tailored efforts for young adults to prevent progression and further reduce overall population prevalence.


Crim1 suppresses left ventricular hypertrophy.
Left ventricular hypertrophy is a leading cause of heart failure and sudden death. Cysteine-rich transmembrane bone morphogenetic protein regulator 1 (Crim1) is expressed at a high level in the heart and has a regulatory role in heart development. The present study aimed to test the hypothesis that Crim1 can have an inhibitory function on ventricular hypertrophy. Rat primary ventricular myocytes were stretched to induce myocyte hypertrophy, and treated with telmisartan or infected with Crim1-expressing recombinant adenovirus (Ad-Crim1). Rat ventricular hypertrophy was induced by abdominal aortic coarctation (AAC), and treated either with telmisartan or myocardial injection of Ad-Crim1 or empty adenovirus vector. The results showed that the expression of Crim1 decreased in the hypertrophic ventricle. The inhibition of angiotensin receptor type 1 (AT1R) by telmisartan in vitro and in vivo significantly increased the expression of Crim1 in the left ventricle. The overexpression of Crim1 by infection with Ad-Crim1 significantly inhibited stretch-induced ventricular myocyte hypertrophy in vitro. The overexpression of Crim1 by gavage with AT1R inhibitor telmisartan or myocardial injection of Ad-Crim1 markedly suppressed AAC-induced left ventricular hypertrophy in vivo. These results suggest that Crim1 has a suppressive function on ventricular hypertrophy and provides a novel therapeutic target for the treatment of cardiac hypertrophy.


[The legal terms "controlled area" and "X-ray room" in the x-ray ordinance of 1973 (author's transl)].
The X-ray Ordinance of 1973 defines the legal terms "controlled area" (sec. 15) and "X-ray room" (sec. 16) differently, serving different legal purposes. For the application and interpretation the two terms are to be distinguished. The competence to locate the limits of the "controlled area" lies with the radiation protection officer according to secs. 11, 12, and 15 of the X-Ray Ordinance. He is authorized to enlarge the "controlled area" and to make its limits identical with those of the X-ray room. The State authorities may intervene in this primary competence of the radiation protection officer only in exceptional cases (15 subsec. 4). The competent State authority may ask the radiation protection officer to enlarge a "controlled area" if it seems necessary for the protection of individuals or of the public. However, a general order of the supervisory authority implicating identical definition of "controlled area" and "X-ray room" would be inconsistent with the explicit provisions of the X-ray Ordinance and therefore unlawful.