Internal structure and thermo-viscoelastic properties of agar ionogels.
Ionic liquids (IL) can alter the physical properties of agar hydrogels. Rheology studies show that gels with wide range of storage moduli (gel strength) G0 values ranging from 1 to 20 KPa could be made in imidazolium based IL solutions where the IL concentration may not exceed 5% (w/v). Gelation and gel melting temperatures (tgel and Tm) could be altered by as much as ≈ 10 °C. Small angle neutron scattering studies revealed the presence of fibre bundles of agar double helices having typical length of 120 nm that increased to ≈ 180 nm under favorable conditions. These structures gain flexibility from the cladding of the agar bundles by IL molecules which in turn caused partial charge neutralization of its surface. Raman spectroscopy revealed differential hydration of these bundles. It was found that IL molecules with longer alkyl chain (more hydrophobic) altered the gel homogeneity, and changed its thermal and mechanical properties significantly. Therefore, customization of agar hydrogels in green solvent medium (IL solutions) widens the scope of its application potential that may include sensing.


Aerosolised heparin in the treatment of Fontan-related plastic bronchitis.
Patients with Fontan palliation and single-ventricle physiology encounter multiple comorbidities including plastic bronchitis, a disease characterised by the plugging of small and large airways by rubbery, white casts. To date, no controlled clinical trials have demonstrated effective treatment of plastic bronchitis. We report the application of aerosolised heparin, which has published success in non-cardiac-related pulmonary disease, for this complication in a Fontan patient.


Tiziana Fuoco.
"My motto is: dare to be different … My favorite time of day is late night when I take time for unspecific thinking and random reading …" Find out more about Tiziana Fuoco in her Introducing … Profile.


Radiation exposure to critical organs in panoramic dental examination.
Nowadays, radiography is a necessary procedure in diagnosis and treatment of patients with dental problems. According to the ALARA (as low as reasonably achievable) principle, dentists must take radiographs of sufficient quality at the lowest possible radiation dose to the patients. The assessment of patient dose on panoramic radiography is difficult because of dynamic nature of the imaging process and the narrow width of the x-ray beam. The present work describes an experiment undertaken using thermoluminescence dosimeters (TLD-100) to obtain the absorbed dose in organs and sensitive tissues in head and neck region during panoramic radiography, based on patient measurement. The overall mean entrance surface dose on thyroid, right and left lens of eyes, parotid glands (right and left) and occipital region in panoramic were 38, negligible, negligible, 367, 319 and 262 μGy, respectively. The results show that there are differences between patient doses examined by different panoramic systems. There is a tendency for lower organ doses for digital compared with analogue panoramic units.


Energy Spectrum CT Image Detection Based Dimensionality Reduction with Phase Congruency.
The image feature detection is widely used in image registration, image stitching and object recognition. The feature detection algorithm can be applied to the detection of artificial images, and can be used to detect the energy spectrum CT image. A new algorithm of phase consistency detection based on dimensionality reduction is proposed in this paper. We mainly focus on the phase congruency of the spectral CT images in the paper and try to use dimensionality reduction to integrate the information of phase congruency detected in the image. The experimental results show that the algorithm can detect the energy spectrum CT image with clear edge and contour, which is beneficial to the subsequent processing. Meanwhile, the algorithm presented is more effective in diagnosis of disease for medical professionals.


Rapid reductions in prices for generic sofosbuvir and daclatasvir to treat hepatitis C.
Novel treatments for hepatitis C demonstrate high cure rates, but current high prices can be a barrier to rapid global treatment scale-up. Generic competition can rapidly lower drug prices. Using data on exports of raw materials in 2015, we calculated currently feasible generic prices of sofosbuvir and daclatasvir. Data on per-kilogram prices of sofosbuvir and daclatasvir active pharmaceutical ingredients (API) exported from India were extracted from an online database. To the cost of the amount of API needed for a 12-week treatment course, we added cost estimates for formulation (40%), packaging (US$0.35/month), and a mark-up (50%). Between 1 January and 15 October 2015, over 5 tons of sofosbuvir were exported, with prices decreasing by US$702/kg/month, and observed prices of US$2501/kg in early September. Over the same period, 84 kg of daclatasvir were exported, with prices decreasing by US$1664/kg/month to US$1897/kg. Using the price estimation algorithm, we estimated the price of a generic sofosbuvir-daclatasvir combination regimen at US$200 per patient for a 12-week treatment course. The costs of generic production of sofosbuvir and daclatasvir are rapidly decreasing. Sofosbuvir-daclatasvir combination treatment could be produced for US$200 per patient per 12-week course.


Cordarone Extravasation Inducing Volkmann's-like Syndrome.
We report a case of Volkmann's-like syndrome occurred after an extravasation of 300 mg of cordarone administrated for a cardiac arrest.The day following the extravasation, an extensive necrosis of the skin and soft tissues occurred. The patient progressively developed a retraction of the muscles of her forearm. To the best of our knowledge this is first the reported case of an acute necrosis of the soft tissue inducing a Volkmann's-like retraction of the upper limb subsequent to a cordarone extravasation. The imaging findings are provided along with a review of the literature.


Telomere associated primase Tap repairs truncated telomeres of Streptomyces.
Replication of the linear chromosomes of soil bacteria Streptomyces proceeds from an internal origin towards the telomeres, followed by patching of the resulting terminal single-strand overhangs by DNA synthesis using terminal proteins as the primer, which remains covalently bound to the 5΄ ends of the DNA. In most Streptomyces chromosomes, the end patching requires the single-strand overhangs, terminal protein Tpg, and terminal associated protein Tap. The telomere overhangs contain several palindromic sequences capable of forming stable hairpins. Previous in vitro deoxynucleotidylation studies indicated that Tap adds the Palindrome I sequence to Tpg, which is extended by a polymerase to fill the gap. In this study, the stringency of Palindrome I sequence was examined by an in vitro deoxynucleotidylation system and in vivo replication. Several nt in Palindrome I were identified to be critical for priming. While the first 3 G on the template were required for deoxynucleotidylation in vitro, deletions of them could be suppressed by the presence of dGTP. In vivo, deletions of these G were also tolerated, and the telomere sequence was restored in the linear plasmid DNA. Our results indicated that the truncated telomeres were repaired by extension synthesis by Tap on the foldback Palindrome I sequence.


The in vivo generation of murine IgD-secreting cells is accompanied by deletion of the C mu gene and occasional deletion of the gene for the C delta 1 domain.
Mature, resting rodent, and primate B lymphocytes express two membrane Ig isotypes, IgM and IgD. Although membrane IgD production by these cells is regulated at a transcriptional level, and does not require deletion of the C mu gene, C mu has been deleted in all of the IgD-secreting tumor cells that have been studied. These IgD-secreting tumors, which include two mineral oil-induced plasmacytomas and three IgD-switch variants of an IgM-secreting hybridoma, might not, however, be representative of the rare IgD-secreting cells generated in response to an immune stimulus. A recent study of mice injected with a goat antibody to mouse IgD has demonstrated the generation of a relatively large secretory IgD response in these animals. We have now produced hybridomas by fusing spleen cells from these mice with a non-Ig-secreting plasmacytoma. Two of these hybridomas, KWD-1 and KWD-2, secrete IgD and express cell membrane IgD. Both of these hybridomas were found to have deleted the C mu gene. KWD-2 produces a delta-chain mRNA and a delta-chain protein similar in size to those previously reported for normal secreted mouse IgD; however, KWD-1 synthesizes a secretory delta-chain mRNA that is approximately 0.25 kb smaller than the KWD-2 secretory delta-chain mRNA and secretes IgD with a delta-chain that is approximately 21 kDa smaller than the secretory delta-chain of KWD-2. ELISA studies with epitope-defined anti-delta mAb indicate that KWD-2 has both delta Fc (C delta 3) [corrected] and delta Fd (C delta 1) [corrected] determinants, whereas KWD-1 has delta Fc but not delta Fd. These studies also demonstrate that the Ag-binding site of KWD-1 is not deleted because KWD-1 specifically binds goat IgG. Northern blot analyses with exon-specific probes indicate that while both KWD-1 and KWD-2 synthesize kappa-chain mRNA and delta-chain mRNA that includes the VH, C delta hinge, and C delta 3 exons, the C delta 1 exon is present only on the KWD-2 delta-chain mRNA. Southern blot analysis confirms that the C delta 1 exon has been deleted in KWD-1, but not KWD-2. We have previously noted that a secretory delta-chain mRNA that is similar in size to that produced by KWD-1 accounts for approximately 25% of the splenic secretory delta-chain mRNA produced by goat anti-mouse IgD antibody-injected mice.(ABSTRACT TRUNCATED AT 400 WORDS)


Optimization of durum wheat bread enriched with bran.
An attempt is made in this study to balance the nutritional and sensory quality of bread. In particular, the formulation of a functional durum wheat bread enriched with bran at high concentration has been developed. Organogel concentration and bran particle size have been used as process variables for bread optimization. Bran concentration was increased at value as high as 15%, thus increasing the nutritional content, even though the sensory quality decreased. Bread was scored barely acceptable at 15% bran concentration. Therefore, the organogel concentration and bran particle size have been optimized to enhance bread sensory quality. Results show that it is possible to prepare bread with a significant bran enrichment without compromising its acceptability by adding proper concentration of organogel and using bran in appropriate particles size.


Experience with ACTH and cortisone in private practice.
ACTH and cortisone are highly nonspecific in their action. A fundamental portion of the mechanism of action is the interposition of a blockade between toxin and end organ. This effect can be of great benefit in the management of a variety of acute and chronic diseases.A major hazard constantly to be kept in mind is the potential masking of advancing disease. This consideration makes concomitant chemotherapy mandatory in the presence of specific infections. In chronic diseased states it should be assumed that prolonged therapy will be necessary. Treatment should not be instituted unless such continued therapy is physiologically and economically feasible.


[Piercing complications in the facial area].
From the ENT specialist's view, the wearing of piercing jewelry on the outer ear, the tongue, the lips, the nose or the eyebrows is the cause of many and sometimes serious local and also systemic complications. Especially on the outer ear allergic reactions, keloid formation, traumatic tears or embedding of the piece of jewelry can occur in addition to simple, superficial infections or perichondritis. Through specific advice, early detection and treatment of complications, serious health damage to the wearer of piercing jewelry can be avoided.


MicroRNA-29a regulates the benzo[a]pyrene dihydrodiol epoxide-induced DNA damage response through Cdc7 kinase in lung cancer cells.
Cdc7 kinase is a key regulator of DNA replication and has an important role in the cellular DNA damage response by controlling checkpoint signaling and cell survival. Yet, how the activity of Cdc7 kinase is regulated is poorly understood. In silico analysis identified microRNA-29 (miR-29)-binding sites in the 3'-untranslated region (UTR) of both Cdc7 and its activating subunit Dbf4. We show that miR-29a binds to Cdc7 and Dbf4 3'-UTRs and regulates kinase levels. We find that in response to DNA damage, upregulation of Cdc7 kinase correlates with a downregulation in miR-29a. Enforced miR-29a expression prevents the accumulation of Cdc7 in response to the environmental genotoxin, benzo[a]pyrene dihydrodiol epoxide (BPDE) present in cigarette smoke, resulting in aberrant checkpoint signaling and increased cell lethality. As BPDE sensitivity was rescued by overexpression of miRNA-resistant Cdc7/Dbf4, we propose that Cdc7 kinase is an important target of miR-29a in determining cell survival from genotoxic stress caused by this environmental toxin.


Nonsurgical bleeding diathesis in anemic thrombocytopenic patients: role of temperature, red blood cells, platelets, and plasma-clotting proteins.
Research at the Naval Blood Research Laboratory (Boston, MA) for the past four decades has focused on the preservation of red blood cells (RBCs), platelets (PLTs), and plasma-clotting proteins to treat wounded servicemen suffering blood loss. We have studied the survival and function of fresh and preserved RBCs and PLTs and the function of fresh and frozen plasma-clotting proteins. This report summarizes our peer-reviewed publications on the effects of temperature, RBCs, PLTs, and plasma-clotting proteins on the bleeding time (BT) and nonsurgical blood loss. The term nonsurgical blood loss refers to generalized, systemic bleeding that is not corrected by surgical interventions. We observed that the BT correlated with the volume of shed blood collected at the BT site and to the nonsurgical blood loss in anemic thrombocytopenic patients after cardiopulmonary bypass surgery. Many factors influence the BT, including temperature; hematocrit (Hct); PLT count; PLT size; PLT function; and the plasma-clotting proteins factor (F)VIII, von Willebrand factor, and fibrinogen level. Our laboratory has studied temperature, Hct, PLT count, PLT size, and PLT function in studies performed in non-aspirin-treated and aspirin-treated volunteers, in aspirin-treated baboons, and in anemic thrombocytopenic patients. This monograph discusses the role of RBCs and PLTs in the restoration of hemostasis, in the hope that a better understanding of the hemostatic mechanism might improve the treatment of anemic thrombocytopenic patients. Data from our studies have demonstrated that it is important to transfuse anemic thrombocytopenic patients with RBCs that have satisfactory viability and function to achieve a Hct level of 35 vol percent before transfusing viable and functional PLTs. The Biomedical Excellence for Safer Transfusion (BEST) Collaborative recommends that preserved PLTs have an in vivo recovery of 66 percent of that of fresh PLTs and a life span that is at least 50 percent that of fresh PLTs. Their recommendation does not include any indication that preserved PLTs must be able to function to reduce the BT and reduce or prevent nonsurgical blood loss. One of the hemostatic effects of RBC is to scavenge endothelial cell nitric oxide, a vasodilating agent that inhibits PLT function. In addition, endothelin may be released from endothelial cells, a potent vasoconstrictor substance,to reduce blood flow at the BT site. RBCs, like PLTs at the BT site, may provide arachidonic acid and adenosine diphosphate to stimulate the PLTs to make thromboxane, another potent vasoconstrictor substance and a PLT-aggregating substance. At the BT site, the PLTs and RBCs are activated and phosphatidyl serine is exposed on both the PLTs and the RBCs. FVa and FXa, which generate prothrombinase activity to produce thrombin, accumulate on the PLTs and RBCs. A Hct level of 35 vol percent at the BT site minimizes shear stress and reduces nitric oxide produced by endothelial cells. The transfusion trigger for prophylactic PLT transfusion should consider both the Hct and the PLT count. The transfusion of RBCs that are both viable and functional to anemic thrombocytopenic patients may reduce the need for prophylactic leukoreduced PLTs, the alloimmunization of the patients, and the associated adverse events related to transfusion-related acute lung injury. The cost for RBC transfusions will be significantly less than the cost for the prophylactic PLT transfusions.


Carotid endarterectomy in patients with renal insufficiency: Should selection criteria be different in patients with renal insufficiency?
The objective of this study was to elucidate the relationship between outcomes from carotid endarterectomy (CEA) in patients with and without renal insufficiency. Carotid endarterectomy is one of the most commonly performed vascular procedures. The role of cardiac comorbidity in carotid endarterectomy has been extensively studied. The relationship between renal failure and surgical outcomes has also been studied for both coronary artery bypass grafting and lower extremity occlusive disease. However, the role of renal insufficiency in relationship to decision making regarding surgical intervention for carotid stenosis is not well defined. The authors hypothesized that the outcomes from CEA were negatively influenced by renal dysfunction. A retrospective review was made of consecutive CEAs performed at their institution from 1990 to 1995. Patients were grouped into 2 categories according to their renal function. Group A, 448 patients (90%) with creatinine level 1.8 mg/dL or less, and group B, 49 patients (10%) with creatinine levels more than 1.8 mg/dL. Data from patients on dialysis are presented but were excluded for the purpose of analysis. Included in the study were 497 patients with a mean age of 70 +/-8.9 and 74 +/-8.9 for groups A and B, respectively. Preoperative creatinine was 1.1 (+/-0.25) mg/dL for group A and 2.5 (+/-0.81) mg/dL for group B. Outcomes were as follows: perioperative cardiac events 5.4% vs 28.6%, stroke rates 2.7% vs 2.0%, and mortality rates 0.9% vs 8.2%, for groups A and B, respectively. At 60-month follow-up the stroke rates were 7.6% vs 6.1 %, and the mortality rates 22.8% vs 59.2%, for groups A and B, respectively. While patients with chronic renal insufficiency have no increased risk of perioperative or long-term neurologic events, perioperative and long-term mortality rates are significantly increased. This significant reduction in survival should prompt a more cautious application of CEA in patients with increased creatinine.


Epidemiological investigation of Borrelia burgdorferi in horses in the municipality of Sinop-MT, Brazil.
Borrelia burgdorferi sensu stricto is the main etiological agent of Lyme disease (LD) in the USA. In Brazil, it is believed that a similar spirochete is the causal agent of the Baggio-Yoshinari syndrome (BYS), a zoonosis also transmitted by ticks, whose clinical manifestations are similar to those of LD. Despite the epidemiological importance, there are no studies reporting the presence and the prevalence of B. burgdorferi among horses in Mato Grosso State. The aim of this study was to detect and measure the frequency of IgG antibodies anti-B. burgdorferi American strain G39/40 in horses in the municipality of Sinop, MT-Brazil, using the indirect enzyme-linked immunosorbent assay (ELISA) for serological diagnosis. Blood samples from 367 horses were collected in 81 farms. An epidemiological questionnaire was applied during the visits to obtain information related to the animals and the farms. From the 367 horses, 214 were positive for B. burgdorferi sensu stricto according to the results of the ELISA test, representing an apparent prevalence of 54.04% [CI = 0.4548051-0.6237234]. Concomitantly, 89 blood samples were taken for molecular analysis by nested polymerase chain reaction (PCR). According to the PCR test results, none of the samples were reactive, although 53 of these samples were reactive according to ELISA. Seventy five farms (92.59%) had at least one reactive horse for B. burgdorferi. Our results support the hypothesis of the presence of anti-Borrelia spp. antibodies in horses in Mato Grosso, reaching a high animal prevalence. Besides that, leisure/sport purposes proved to be a risk factor, with an odds ratio of 3.16. These findings clearly indicate the need of borreliosis control in Sinop and make a significant contribution to the knowledge of the disease in Mato Grosso.


The use of propensity scores in pharmacoepidemiologic research.
To describe the application of propensity score analysis in pharmacoepidemiologic research using a study comparing the renal effects of two commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs). Observational data were collected on the change in renal function, as measured by serum creatinine concentration, before and after use of two NSAIDs, Ibuprofen and Sulindac. To estimate the treatment effect of the different NSAIDs, we used the propensity score methodology to reduce the potential confounding effects caused by unbalanced covariates. After estimating the propensity scores (the probabilities of each patient being prescribed Sulindac) from a logistic regression model, we stratified the data based on sample quintiles of the propensity score distribution. The final estimate of the treatment effect was then obtained by averaging the treatment estimates from the stratified samples. Initially, 23 covariates differed significantly between the two treatment groups. Using the propensity score methodology, we were able to balance the distributions of 16 covariates. The imbalances in the remaining seven covariates were also greatly reduced. Although the use of either drug resulted in a decrease in renal function, overall differences between them were not statistically significant with respect to their effect on creatinine concentrations based on the propensity score analysis. Observational studies often produce treatment groups that are not directly comparable due to imbalances in covariate distributions between the treatment groups. Propensity score analysis provides a simple and effective way of controlling the effects of these covariates and obtaining a less biased estimate of the treatment effect. Copyright (c) 2000 John Wiley & Sons, Ltd.


Elevated serum human epididymis protein 4 is associated with disease severity and worse survival in idiopathic pulmonary fibrosis: a cohort study.
Elevated expression of human epididymis protein 4 (HE4) was previously described in connective tissue disease-associated interstitial lung diseases (CTD-ILDs) and cystic fibrosis (CF), but the clinical significance of HE4 has remained unknown in idiopathic pulmonary fibrosis (IPF), which is a progressive fibrosing ILD with a heterogeneous course that is in urgent need of reliable biomarkers in its clinical practice. A total of 27 IPF patients with acute exacerbation status (AE-IPF), 32 IPF patients with stable status (S-IPF), and 29 sex-age matched healthy controls were retrospectively included. The levels of serum HE4 and Krebs von den Lungen-6 (KL-6) of the 3 cohorts were measured. In addition, the pulmonary expression of HE4 was evaluated in lung transplant specimens of IPF using immunohistochemistry and Western blot, and noncancerous lung tissue resected from early-stage lung cancer patients as controls. The endpoint of follow-up was March 1st, 2022, and the Cox regression model was used to analyze the prognostic value of HE4. The levels of HE4 and KL-6 were obviously elevated in AE-IPF patients compared to S-IPF (296.4 vs. 178.1 pmol/L for HE4, P<0.001; 2,007.0 vs. 990.5 IU/mL for KL-6, P<0.001) or healthy controls (296.4 vs. 51.8 pmol/L for HE4, P<0.001; 2,007.0 vs. 181.0 IU/mL for KL-6, P<0.001). Significant correlations were observed between serum HE4 levels and percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (r=-0.526, P<0.001), percent predicted forced vital capacity (FVC%) (r=-0.344, P=0.024), gender-age-physiology (GAP) index (r=0.535, P<0.001), and oxygenation index (r=-0.550, P<0.001) in IPF patients. In histological analysis, overexpression of HE4 in mucosal epithelium of dilated bronchi was observed in IPF patients compared with controls. Multivariate cox regression revealed that serum levels of HE4 [hazard ratio (HR) =1.004, P=0.042] and GAP index (HR =1.374, P=0.010) were associated with worse survival in IPF patients. The expression of serum HE4 was obviously elevated in IPF patients, especially in AE-IPF patients. In addition, serum HE4 could be utilized as a biomarker of disease severity and poor prognosis of IPF patients. These findings warrant further validation in larger, multi-center, and longitudinal cohorts.


The internalization of nerve growth factor by high-affinity receptors on pheochromocytoma PC12 cells.
The internalization and subsequent fate of the two populations of nerve growth factor (NGF) receptors on pheochromocytoma PC12 cells were explored either by identifying the relative amounts and sizes of the receptors, after incubation of cells with [125I]NGF, by cross-linking with a photoreactive heterobifunctional reagent or by following the topological distribution of the cross-linked receptors with time. The ratio of the slow, high-affinity to the fast, low-affinity NGF receptor decreased over a 5-h incubation with [125I]NGF in a process which did not involve proteolytic conversion of the slow to the fast receptor. During this period the cross-linked slow receptor moved from a trypsin-labile to a trypsin-stable site suggestive of internalization. In contrast, the cross-linked fast NGF receptor remained trypsin sensitive for at least 2 h of incubation, indicative of a constant cell surface localization. The internalized [125I]NGF in the cross-linked slow NGF receptor was not degraded, indicating that cross-linking, by preventing the acid pH-induced dissociation of the NGF-receptor complex in the endosomes, blocks normal sorting of [125I]NGF to the lysosomes. The cross-linked receptor was not recycled to the cell surface. If this reflects the properties of the unmodified receptor then another process, possibly receptor conversion, is required to replenish slow NGF receptors in the cell surface.


Characterization of Enterococcus faecium with macrolide resistance and reduced susceptibility to quinupristin/dalfopristin in a Japanese hospital: detection of extensive diversity in erm(B)-regulator regions.
Cross-resistance to macrolide, lincosamide, and streptogramin B (MLSB) antibiotics is mainly mediated by the erm (erythromycin ribosome methylation) genes that encode 23S rRNA methylases in enterococi, and various mechanisms are involved in the streptogramin B resistance. Prevalence of MLSB resistance and its genetic mechanisms were analyzed for a total of 159 strains of Enterococcus faecium isolated from clinical specimens in a university hospital in Japan from 1997 to 2006. Resistance to erythromycin (EM) and clindamycin was detected in 88.1% and 89.9% of all the strains examined, respectively, and expression of resistance was totally constitutive. Although none of the strain was resistant to quinupristin/dalfopristin (Q/D), 28 strains (17.6%) showed intermediate resistance to Q/D (MIC: 2 μg/ml). The erm(B) gene was detected in 139 strains (87.4%), and msrC was found in all the strains examined, whereas no other known MLSB resistance genes were identified. The erm(B) regulator region (RR) containing a coding region of the leader peptide was classified into 13 genetic variations (L1-L3, M, S1-S7, D, and R genotypes) in 56 strains. However, no relatedness was identified between the erm(B) RR genotype and EM resistance, or reduced susceptibility to Q/D, although most of Q/D-intermediate strains were assigned to the L1, L2, and S1 genotypes. Q/D-intermediate strains were classified into five multiple-locus variable-number tandem-repeat analysis (MLVA) types, including four types of clonal complex (CC)-C1, five sequence types (STs), including four STs of CC-17, and several resistance gene/virulence factor profiles. The present study revealed the occurrence of Q/D-intermediate E. faecium, which are composed of heterogeneous strains in Japan, and more genetic diversity in the erm(B) RRs than those reported previously.


Indirect calorimetry in humans: a postcalorimetric evaluation procedure for correction of metabolic monitor variability.
Indirect calorimetry (IC) with metabolic monitors is widely used for noninvasive assessment of energy expenditure and macronutrient oxidation in health and disease. To overcome deficiencies in validity and reliability of metabolic monitors, we established a procedure that allowed correction for monitor-specific deviations. Randomized comparative IC (canopy mode) with the Deltatrac MBM-100 (Datex) and Vmax Encore 29n (SensorMedix) was performed in postabsorptive (overnight fast >8 h) healthy subjects (n = 40). In vitro validation was performed by simulation of oxygen consumption (VO2) and carbon dioxide output (VCO2) rates by using mass-flow regulators and pure gases. A simulation-based postcalorimetric calibration of cart readouts [individual calibration control evaluation (ICcE)] was established in adults (n = 24). The comparison of carefully calibrated monitors showed marked differences in VCO2 and VO2 (P < 0.01) and derived metabolic variables [resting energy expenditure (REE), respiratory quotient (RQ), glucose/carbohydrate oxidation (Gox), and fat oxidation (Fox); P < 0.001]. Correlations appeared to be acceptable for breath gas rates and REE (R(2) ~ 0.9) but were unacceptable for RQ (R(2) = 0.3), Gox, and Fox (R(2) = 0.2). In vitro simulation experiments showed monitor-dependent interferences for VCO2 and VO2 as follows: 1) within series, nonlinear and variable deviations of monitor readouts at different exchange rates; 2) between series, differences and unsteady variability; and 3) differences in individual monitor characteristics (eg, rate dependence, stability, imprecision). The introduction of the postcalorimetric recalibration by ICcE resulted in an adjustment of gas exchange rates and the derived metabolic variables with reasonable correlations (R(2) > 0.9). Differential, metabolic, monitor-specific deviations are the primary determinants for lack of accuracy, comparability, and transferability of results. This problem can be overcome by the present postcalorimetric ICcE procedure.


Intrastriatal grafts of rat colonic smooth muscle lacking myenteric ganglia stimulate axonal sprouting and regeneration.
Grafts of living or freeze-killed freshly dissected colonic smooth muscle from young inbred Fischer rats were implanted into the corpus striatum of adult Fischer rats. Sections of brain were examined electron microscopically 3 and 6 wk after implantation. At both times, living grafts were vascularised and contained healthy differentiated smooth muscle cells, fibroblasts, interstitial cells of Cajal and some macrophages. Large bundles of small nonmyelinated axons, identified as CNS axonal sprouts, could be observed in the brain at and near the interface between the living smooth muscle and the CNS tissue. Bundles of regenerating CNS axons, often associated with astrocyte processes, had grown into the grafts. Some axons within the grafts had matured, enlarged and become myelinated by oligodendrocyte processes or Schwann cells. In some cases, smooth muscle cells were observed in close and intricate association with axons. In contrast to the living grafts, grafts of freeze-killed smooth muscle, examined 3 and 6 wk after implantation, contained macrophages, fibroblasts, collagen and large amounts of cellular debris, but no living muscle cells, astrocytes or Schwann cells. The striatal neuropil around freeze-killed grafts did not contain large bundles of CNS axonal sprouts and bundles of axons were not observed within the freeze-killed graft. This study demonstrates that cells from the smooth muscle layers of the colon, in the absence of myenteric ganglia, can stimulate a vigorous regenerative response from CNS axons when implanted into the corpus striatum of adult rats.


An update on liposomes in drug delivery: a patent review (2014-2018).
Introduction: Pharmacotherapy is limited by the inefficient drug targeting of non-healthy cells/tissues. In this pharmacological landscape, liposomes are contributing to the impulse given by Nanotechnology to optimize drug therapy. Areas covered: The analysis of the state-of-the-art in liposomal formulations for drug delivery purposes have underlined that lately published patents (since 2014) are exploring alternative compositions and ways to optimize the stability and drug loading content/release profile. These improvements are complemented by improved long-circulating structures and further liposome functionalizations, which have definitively opened the road for the (co-)delivery of therapeutics to the site of action. Liposomes are also contributing to new drug delivery approaches involving the generation of extracellular vesicles by targeted cells, while opening new ways to combine disease diagnosis and therapy (theranosis). Expert opinion: Patent publications on liposomal formulations have expanded new ways in drug delivery. New lipid compositions and strategies to optimize stability and drug vehiculization capabilities have settle solid pillars in liposome fabrication. Despite, their architecture has been satisfactorily adapted for combining passive and active drug targeting concepts, new inputs of liposomes into the disease arena should answer for: a simple/scalable/cost-effective formulation; a safe/stable/controllable formulation meeting quality control regulations; and, a confirmed therapeutic efficiency in clinical investigations.


Palliative Care for Patients With Heart Failure: An Integrative Review.
Palliative care should be integrated into routine disease management for all patients with serious illness, regardless of settings or prognosis. The purposes of this integrative review were to identify the features of randomized controlled trials for adult patients with heart failure and to provide basic references for the development of future trials. Using Whittemore and Knafl's integrative literature review method, comprehensive searches of the PubMed, Cochrane Library, CINAHL, EMBASE, and Korean databases were conducted, integrating keywords about heart failure and palliative care interventions. Quality appraisal was assessed using Cochrane risk-of-bias tools. In total, there were 6 trials providing palliative care interventions integrating team-based approaches between palliative care specialists and nonpalliative clinicians, such as a cardiologist, cardiac nurse, and advanced practice nurse across inpatient and outpatient settings. The different types of interventions included home visits, symptom management via phone calls or referral to a specialist team, and the establishment of treatment planning. Patient-reported outcome measures included positive effects of palliative interventions on symptom burden and quality of life. Given that most of the selected studies were conducted in Western countries, palliative care should be culturally tailored to assist heart failure patients worldwide.


Synthesis and biological evaluation of N-substituted sophocarpinic acid derivatives as coxsackievirus B3 inhibitors.
A series of novel N-substituted sophocarpinic acid derivatives was designed, synthesized, and evaluated for their anti-enteroviral activities against coxsackievirus type B3 (CVB3) and coxsackievirus type B6 (CVB6) in Vero cells. Structure-activity relationship analysis revealed that the introduction of a benzenesulfonyl moiety on the 12-nitrogen atom in (E)-β,γ-sophocarpinic acid might significantly enhance anti-CVB3 activity. Among the derivatives, (E)-12-N-(m-cyanobenzenesulfonyl)-β,γ-sophocarpinic acid (11 m), possessing a meta-cyanobenzenesulfonyl group, exhibited potent activity against CVB3 with a selectivity index (SI) of 107. Furthermore, compound 11 m also showed a good oral pharmacokinetic profile, with an AUC value of 7.29 μM h⁻¹ in rats, and good safety through the oral route in mice, with an LD₅₀ value of >1000 mg kg⁻¹; these values suggest a druggable characteristic. Therefore, compound 11 m was selected for further investigation as a promising CVB3 inhibitor. We consider (E)-β,γ-N-(benzenesulfonyl)sophocarpinic acids to be a novel class of anti-CVB3 agents.


The effectiveness of guideline implementation strategies on improving antipsychotic medication management for schizophrenia.
To compare the effectiveness of a conceptually-based, multicomponent "enhanced" strategy with a "basic" strategy for implementing antipsychotic management recommendations of VA schizophrenia guidelines. Two VA medical centers in each of 3 Veterans Integrated Service Networks were randomized to either a basic educational implementation strategy or the enhanced strategy, in which a trained nurse promoted provider guideline adherence and patient compliance. Patients with acute exacerbation of schizophrenia were enrolled and assessed at baseline and 6 months and their medical records were abstracted; 291 participants were included in analyses. Logistic regression models were developed for rates of: (1) switching patients from first-generation antipsychotics (FGA) to second-generation antipsychotics (SGA), and (2) guideline-concordant antipsychotic dose. Of participants prescribed FGAs at baseline, those at enhanced sites were significantly more likely than participants at basic sites to have an SGA added to the FGA during the study (29% vs. 8%; adjusted OR = 7.7; 95% CI: 2.0-30.1), but were not significantly more likely to be switched to monotherapy with an SGA (29% vs. 23%). Guideline-concordant antipsychotic dosing was not significantly affected by the intervention. The enhanced guideline implementation strategy increased addition of SGAs to FGA therapy, but did not significantly increase guideline-recommended switching from FGA to SGA monotherapy. Antipsychotic dosing was not significantly altered. The study illustrates the challenges of changing clinical behavior. Strategies to improve medication management for schizophrenia are needed, and must incorporate recommendations likely to emerge from recent research suggesting comparable effectiveness of SGAs and FGAs.


Characterization of the reactivity and chlorinated products of carbazole during aqueous chlorination.
Carbazole in source water is a potential precursor for toxic chlorocarbazoles in drinking water when chlorine is used as a disinfection agent in drinking water treatment plants. However, the reactivity of carbazole and the specific structures and predominant analogues of chlorocarbazoles produced during aqueous chlorination remain unknown. In this study, the aqueous chlorination of carbazole was performed to characterize its reactivity and the chlorinated products. Chlorocarbazoles generated from carbazole were identified by a comprehensive two-dimensional gas chromatography-mass spectrometry method, and their molecular structures were predicted by the Fukui index of electrophilic attack, f-1(r). As a result, the comprehensive chlorination pathway of carbazole was extrapolated with a total of nine chlorocarbazoles identified, including two monochlorocarbazoles (3-chlorocarbazole and 1-chlorocarbazole), four dichlorocarbazoles (3,6-dichlorocarbazole, 1,6-dichlorocarbazole, 1,3-dichlorocarbazole and 1,8-dichlorocarbazole), two trichlorocarbazoles (1,3,6-trichlorocarbazole and 1,3,8-trichlorocarbazole) and one tetrachlorocarbazole (1,3,6,8-tetrachlorocarbazole). The f-1(r) value indicates that the C1, C3, C6 and C8 atoms of carbazole were the favored positions for electrophilic attack, with the C3 and C6 atoms being the predominant sites for chlorine substitution. 3-Chlorocarbazole, 3,6-dichlorocarbazole, 1,3,6-trichlorocarbazole and 1,3,6,8-tetrachlorocarbazole were the major analogues of each chlorocarbazole group; however, the production of minor analogues such as 1-chlorocarbazole and 1,6-dichlorocarbazole should not be overlooked. The chlorination of carbazole was a pseudo first order reaction with a reaction rate of 0.1836 nmol/(L· h) and half-life of 3.77 h (pH = 6.4, Cl2 = 4.7 mg/L), and the chlorination rate of carbazole was approximately 5 times faster than that of an known chlorination precursor pyrene. These results showed that Fukui index was efficacious to predict the chlorination sites of aromatic compounds, and that carbazole is readily transformed into toxic chlorocarbazoles in drinking water treatment plants that use chlorine as a disinfection agent.


Imaging of gunshot injuries in a west Dublin teaching hospital--a ten year review.
There has been an increase in gun-related crime in Ireland over the last decade to gangland violence, especially in west Dublin. This places a burden on hospital services not previously encountered. The aim of this study was to examine the demographics of gunshot: injuries presenting to a Dublin teaching hospital, and the impact on radiology over a ten year period. A total of 65 gunshot injuries were seen. Mortality for high velocity wounds was much higher (10/23, 43%) than for low-velocity shotgun injuries (2/34, 6%).


Performance of QuantiFERON-TB Gold In-Tube (QFTGIT) for the diagnosis of Mycobacterium tuberculosis (Mtb) infection in Afar Pastoralists, Ethiopia.
Currently, T-cell based gamma interferon (IFNγ) release assays (IGRAs) are acknowledged as the best methods available for the screening of latent tuberculosis infection (LTBI) and also as aid for the diagnosis of active tuberculosis (TB). To our information, the performance of these diagnostic tests has not been evaluated in Ethiopia. Therefore, the intent of this study was to evaluate the performance of QuantiFERON-TB Gold In-Tube (QFTGIT) in patients clinically suspected of active pulmonary TB (PTB) as well as in healthy subjects prior to its utilization for the epidemiological study of active TB and LTBI in Afar pastoralists. The sensitivity of QFTGIT was evaluated in 140 subjects who were clinically suspected of PTB using the cut-off value recommended by the manufacturer (≥ 0.35 IU/ml) and disease-specific cut-off value. Sputum culture result was used as a gold standard. The specificity of the test was evaluated both in patients and in 55 tuberculin skin test (TST) negative healthy subjects. Out of the 140 study participants, 37 (26.4%) were positive for active PTB by culture. Out of the 37 subjects who had positive results by culture, 6 individuals were HIV-seropositive. Out of the 103 subjects who were negative by culture, 6 subjects had indeterminate results and 21 were HIV-seropositive. The performance of the test was assessed using data from 107 (31 culture positive and 76 culture negative) individuals who were clinically suspected of PTB and HIV-seronegatives. Using the manufacturer recommended cut-off value, the sensitivity of the test was 64.5% (20/31), while its specificity was 36.8% (28/76). The sensitivity of the test was increased to 77.4%, while the specificity was reduced to 23.7% using a cut-off value ≥ 0.1 IU/ml of IFNγ as disease-specific cut-off value. In TST negative healthy subjects, the specificity of the test was 58.2%. Our findings revealed a low sensitivity of QFTGIT in the diagnosis of Mycobacterium tuberculosis (Mtb) infection in the present study area using the cut-off value recommended by the manufacturer. Nevertheless, the sensitivity increased from 64.5% to 77.4% by lowering the cut-off value recommended by the manufacturer to ≥ 0.1 IU/ml of IFNγ level. Hence, it is of practical importance to evaluate the performance of QFTGIT in population under different settings prior to its application either for the diagnosis of active TB or LTBI.


Preventive and therapeutic effects of natural products and herbal extracts on nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.
Nonalcoholic fatty liver disease (NAFLD) is a common condition that is prevalent in patients who consume little or no alcohol, and is characterized by excessive fat accumulation in the liver. The disease is becoming increasingly common with the rapid economic development of countries. Long-term accumulation of excess fat can lead to NAFLD, which represents a global health problem with no effective therapeutic approach. NAFLD is a complex, multifaceted pathological process that has been the subject of extensive research over the past few decades. Herbal medicines have gained attention as potential therapeutic agents to prevent and treat NAFLD due to their high efficacy and low risk of side effects. Our overview is based on a PubMed and Web of Science database search as of Dec 22 with the keywords: NAFLD/NASH Natural products and NAFLD/NASH Herbal extract. In this review, we evaluate the use of herbal medicines in the treatment of NAFLD. These natural resources have the potential to inform innovative drug research and the development of treatments for NAFLD in the future.


Molecular modelling of cytochrome P4502D6 (CYP2D6) based on an alignment with CYP102: structural studies on specific CYP2D6 substrate metabolism.
1. A molecular model of CYP2D6 has been constructed from the bacterial form CYP102 via a homology alignment between the CYP2D subfamily and CYP102 protein sequences. 2. A number of typical CYP2D6 substrates are shown to fit the putative active site of the enzyme, as can the specific inhibitor quinidine. 3. Some of the allelic variants in CYP2D6, which give rise to genetic polymorphisms in 2D6-mediated metabolism, can be rationalized in terms of their position within the active site region. 4. The results of site-directed mutagenesis experiments are consistent with the CYP2D6 model generated from the CYP102 crystal structure. 5. The possibility of an alternative orientation within the active site may explain the CYP2D6-mediated metabolism of relatively large-sized substrates.


Retinal Cell Transplantation, Biomaterials, and In Vitro Models for Developing Next-generation Therapies of Age-related Macular Degeneration.
Retinal pigment epithelium (RPE) cells grown on a scaffold, an RPE patch, have potential to ameliorate visual impairment in a limited number of retinal degenerative conditions. This tissue-replacement therapy is suited for age-related macular degeneration (AMD), and related diseases. RPE cells must be transplanted before the disease reaches a point of no return, represented by the loss of photoreceptors. Photoreceptors are specialized, terminally differentiated neurosensory cells that must interact with RPE's apical processes to be functional. Human photoreceptors are not known to regenerate. On the RPE's basal side, the RPE transplant must induce the reformation of the choriocapillaris, thereby re-establishing the outer blood-retinal barrier. Because the scaffold is positioned between the RPE and choriocapillaris, it should ideally degrade and be replaced by the natural extracellular matrix that separates these tissues. Besides biodegradable, the scaffolds need to be nontoxic, thin enough to not affect the focal length of the eye, strong enough to survive the transplant procedure, yet flexible enough to conform to the curvature of the retina. The challenge is patients with progressing AMD treasure their remaining vision and fear that a risky surgical procedure will further degrade their vision. Accordingly, clinical trials only treat eyes with severe impairment that have few photoreceptors to interact with the transplanted patch. Although safety has been demonstrated, the cell-replacement mechanism and efficacy remain difficult to validate. This review covers the structure of the retina, the pathology of AMD, the limitations of cell therapy approaches, and the recent progress in developing retinal therapies using biomaterials.


Impaired adaptation of the hypothalamic-pituitary-adrenal axis to chronic ethanol stress in aged rats.
Acute injection of ethanol in young rats stimulates corticosterone secretion, and repeated daily ethanol injection results in tolerance to this response. This study examined the tolerance development of the corticosterone response to 14 daily ethanol injections (2 g/kg i.p.) in young (3-month-old) and aged (24-month-old) male rats. By day 7 the young rats exhibited complete tolerance to the stimulatory effects of ethanol on corticosterone levels, as measured 1 h after injection. In contrast, the aged rats displayed a fairly large corticosterone response to ethanol on day 7, and they still exhibited a significant corticosterone response to ethanol on day 14. There was no difference between young and aged rats in blood ethanol levels at any time point examined, and blood ethanol levels did not change across days of treatment, indicating that neither the tolerance development, nor the age-related difference in tolerance development could be explained by time- and age-related differences in ethanol metabolism. There also was little evidence for the impaired tolerance development in the aged rats to be secondary to a generalized dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis following 2 weeks of ethanol treatment. Thus, there was no difference in basal corticosterone levels between young and aged rats on each test day, and there was no difference between young and aged rats in the corticosterone response to an acute restraint stress challenge when administered 24 h after the last day of ethanol treatment. This study suggests that in aged rats there are changes in the adaptive mechanisms contributing to tolerance of the HPA axis response to ethanol.


Diametral tensile strength of novel fast-setting calcium silicate cement.
Novel fast-setting calcium silicate cement with fluoride (CSC) has been developed for potential applications in tooth crown. The aim of this study was to test the diametral tensile strength (DTS) of different CSC compositions in humid condition on day1, 28, and 180. We tested 'bond CSC' with 3.5% fluoride and no radiocontrast, 'CSC' with 3.5% fluoride and 10% radiocontrast, 'ultrafast CSC' with 3.5% fluoride and 20% radiocontrast, 'high fluoride CSC' with 15% fluoride and 25% radiocontrast, Biodentine, and MTA. We filled the cements after mixing to cylindrical molds. Specimens were stored in >95% humidity. DTS was measured at each time point. CSC compositions had statistically higher DTS compared to MTA and Biodentine on day1. Bond CSC showed higher DTS versus all cements, except CSC, at all time points. DTS of all cements, except Biodentine, significantly increased in humid condition on day28 and day180 compared to day1.


Detailed physical map of human chromosomal region 11q12-13 shows high meiotic recombination rate around the MEN1 locus.
We have constructed a physical map of the region q12-13 on chromosome 11 by combining data generated from a panel of radiation-reduced somatic cell hybrids and pulsed-field gel electrophoresis (PFGE). Twenty different genetic markers have been sublocalized and ordered within this region and a total of 8.0 megabases has been mapped in detail using rare-cutting restriction endonucleases and PFGE. In two instances, the long-range restriction PFGE map spans the total distance between pairs of loci that have been previously mapped by genetic linkage in reference families. Comparison of this physical map with the available linkage map indicates a great variation in the recombination frequency over the region. The recombination rate is higher than expected, particularly for markers flanking the MEN1 region. Thus, for the closest pair of linked markers on the centromeric side, one centimorgan corresponds to approximately 300 kilobases, and for markers on the telomeric side, one centimorgan corresponds to approximately 350-600 kilobases.


Morphology-Preserving Sensitization of ZnO Nanorod Surfaces via Click-Chemistry.
Films of ZnO nanorods grown by chemical vapor deposition were functionalized with a chromophore in a stepwise process that preserves the surface morphology. In the first step, the ZnO nanorods were functionalized by exposure to prop-2-ynoic acid (propiolic acid) in vacuum, which did bind through the COOH group leading to a ZnO surface functionalized with ethyne moieties (ethyne/ZnO). In the second step, 9-(4-azidophenyl)-2,5-di-tert-butylperylene (DTBPe-Ph-N3) was reacted with the ethyne/ZnO surface via copper-catalyzed azide-alkyne click reaction (CuAAC) in solution to form the DTBPe-functionalized surface (DTBPe/ZnO). The ZnO morphology was preserved after each step, as demonstrated by scanning electron microscopy (SEM). Each step was probed by X-ray photoelectron spectroscopy (XPS), and transient absorption spectroscopy (TA) of the resulting DTBPe/ZnO surface shows interfacial electron transfer following visible light excitation. As expected, attempts to bind the reference compound 1-(4-(8,11-ditert-butylperylen-3-yl)-phenyl)-1H-1,2,3-triazole-4-carboxylic acid (DTBPe-Ph-Tz-COOH) directly from solution lead to etched surfaces (confirmed by SEM) and undefined binding modes (confirmed by TA).


Seizures, antiepileptics, antioxidants and oxidative stress: an insight for researchers.
Neuronal hyperexcitability and excessive production of free radicals have been implicated in the pathogenesis of a considerable range of neurological disorders, including epilepsy. The high rate of oxidative metabolism, coupled with the low antioxidant defenses and the richness in polyunsaturated fatty acids, makes the brain highly vulnerable to free radical damage. The increased susceptibility of the brain to oxidative damage highlights the importance of understanding the role of oxidative stress in the pathophysiology of seizures. The present review aims not only to address the link between mitochondrial dysfunction, oxidative stress and seizures, but also the modulation of the pro-oxidant/antioxidant balance following seizures and treatment with antioxidants and antiepileptic drugs. A literature review revealed that there are articles that address the role of oxidative stress and mitochondrial dysfunction in neurological disorders, including those involving different seizure models where the modulation of the pro-oxidant/antioxidant balance by seizures per se and by antioxidant agents is discussed. However, the critical role of oxidative stress in all seizure models is not uniform. Therefore, there is a need for a review article that will address all these issues together. The experimental and clinical data suggest a putative role of oxidative stress in the pathophysiology of certain seizure types. The pro-oxidant/antioxidant balance is not only modulated by seizures per se, but also by antiepileptic drugs. The ability of antioxidants for reducing the seizure manifestations and the accompanying biochemical changes (i.e., markers of oxidative stress) further supports a role of free radicals in seizures and highlights a possible role of antioxidants as adjuncts to antiepileptic drugs for better seizure control.


[May eccentric training be effective in the conservative treatment of chronic supraspinatus tendinopathies? A review of the current literature].
Eccentric training (ET) has been shown to be an effective conservative treatment option for chronic patellar and Achilles tendinopathies. As part of the four-muscle-tendon-complex of the rotator cuff, the supraspinatus is involved most commonly in shoulder disorders. Histopathologic alterations of the supraspinatus tendon are comparable to findings in lower extremity tendinopathies. Hence, the question arises whether the concept of eccentric training can be successfully transferred to the upper extremity. Yet, no randomised controlled trials have been published to support this theory. This problem emerges from the fact that the supraspinatus is part of a complex functional unit. Consequently, surrounding soft tissues are frequently concomitantly affected. The inherent etiology and genesis of pathologic alterations in the supraspinatus tendon and its influence on shoulder disorders is not clear to date. However, the apparent success of ET in managing tendinopathies of the lower extremity urges further scientific work for developing evidence-based guidelines for the conservative treatment of tendinopathies in the shoulder region. Taking into account this lack of data as well as the anatomical and functional constraints, the aim of this work is to review the current state of the literature.


Comparison and assessment of the difference in total dietary fiber in cooked dried legumes as determined by five methods.
Dried beans (kidney and great northern) and dried peas (chick, green, and yellow) were cooked according to package instructions. Total dietary fiber (TDF) was measured by the Mongeau (AOAC 992.16), Prosky (AOAC 985.29), and Lee (AOAC 991.43) methods (A, B, and C, respectively). Nonstarch polysaccharides (NSP) were measured by the Englyst gas-chromatographic method that included dimethyl sulfoxide treatment, and the lignin measured separately was added to NSP (method D). TDF was also measured by the Li method (E). TDF values ranged from 7 to 48 g/100 g dry weight. Methods B and C gave similar TDF values, which were higher than those from other methods. For kidney beans I, TDF values by methods B and C were up to 2.5 times higher because of the inclusion of starch. The fiber residues from methods A and C contained the same amounts of arabinose, xylose, mannose, galactose, and uronic acid, but glucose was 4 times higher in residue C than in residue A. When alpha-amylase from porcine pancreas was incorporated in methods B or C for 5 samples, the discrepancies among methods A, B, and C were reduced by 60-98%.


A high amount of branched chain amino acids did not change favourable plasma albumin and protein concentrations during 48 hours post-laparotomy infusion--an experimental study in the rabbit.
The changes in plasma albumin and protein concentration during 48 hours post-laparotomy infusion of saline, 10% glucose alone and in combination with low (18%) and high (25%) concentration of branched chain amino acid solutions were investigated in the rabbit. During 24-hours post-laparotomy infusion of a solution with a low concentration of branched chain amino acids together with 10% glucose, the plasma albumin concentration decreases (15%) less than during infusion of a solution with a high concentration of branched chain amino acids together with 10% glucose (24%), saline (21%) or 10% glucose alone (23%). The amount of decrease in plasma albumin concentration 48 hours after laparotomy was independent of the four solution regimen used (between 20 to 23%). There is no favourable effect on plasma albumin and protein concentration from the use of high amounts of branched chain amino acids in 48 hours post-laparotomy infusion, whereas 24 hours infusion of a low concentration of branched chain amino acids is recommended.


Posters Presented at North American Skull Base Society 2016-2018: What Factors Influence Their Publication?
Objective Research productivity impacts an individual's academic credentials and serves to advance the field of neurosurgery at large. Poster presentations allow researchers to share preliminary results with respected colleagues; however, more critical is the ability to publish peer-reviewed articles. Key factors that lead posters to journal publication are not well understood and difficult to quantify. This study investigates the association between bibliometrics of authors who presented posters at the North American Skull Base Society (NASBS) meeting and odds of journal publication. Methods Posters from the 2016 to 2018 NASBS archive were reviewed. Hirsch-index (h-index) of first (FH) and senior (SH) authors, research type, research topic, and number of poster authors (nAuthPost) were collected. For posters published as journal articles, number of days from poster presentation to publication (nDays), number of authors in published articles (nAuthArt), and journal impact factor (JIF) were recorded. Results One-hundred sixty-nine of 481 posters (35.1%) were published as articles. Median FH and SH for published versus unpublished posters were 7 versus 5 ( p = 0.01) and 29 versus 19 ( p < 0.001), respectively. When adjusted with multivariate regression, only SH ( p < 0.001) and nAuthPost ( p = 0.001) were significantly associated with odds of publication. Median (interquartile range [IQR]) nDays was 361 (394). Increased authors from poster to article ( p = 0.017) and lower FH ( p = 0.08) were correlated with increased time to publication. Median (IQR) JIF for all publications was 1.723 (1.068). Conclusions Bibliometrics such as h-index and number of authors from posters can help objectively characterize and predict future success in research productivity.


High-speed measurement of rotational anisotropy nonlinear optical harmonic generation using position-sensitive detection.
We present a method of performing high-speed rotational anisotropy nonlinear optical harmonic generation experiments at rotational frequencies of several hertz by projecting the harmonic light reflected at different angles from a sample onto a stationary position-sensitive detector. The high rotational speed of the technique, 10(3) to 10(4) times larger than existing methods, permits precise measurements of the crystallographic and electronic symmetries of samples by averaging over low frequency laser-power, beam-pointing, and pulse-width fluctuations. We demonstrate the sensitivity of our technique by resolving the bulk fourfold rotational symmetry of GaAs about its [001] axis using second-harmonic generation.


Structural determinants of the Alzheimer's amyloid beta-peptide.
The hallmark event of Alzheimer's disease (AD) is the deposition of amyloid as insoluble fiber masses in extracellular neuritic plaques and around the walls of cerebral blood vessels. The main component of amyloid is a hydrophobic peptide, named amyloid beta-peptide (beta A4), which results from the processing of a much longer membrane amyloid precursor protein (APP). This review focuses on the structural features of beta A4 and the factors that determine beta A4 insolubilization. Theoretical and experimental studies of the primary structure of beta A4 have shown that it is composed of a completely hydrophobic C-terminal domain, which adopts beta-strand structure, and an N-terminal region, whose sequence permits different secondary structures. In fact, this region can exist as an alpha-helical or beta-strand conformation depending on the environmental condition (pH and hydrophobicity surrounding the molecule). The effects of pH and hydrophobicity on beta A4 structure may elucidate the mechanisms determining its aggregation and amyloid deposition in AD.


Reversal of renal failure and paraplegia after thoracoabdominal aneurysm repair.
Repair of ruptured thoracoabdominal aortic aneurysms is complicated by high rates of perioperative paraplegia, renal insufficiency, and mortality. This report describes a patient with a ruptured thoracoabdominal aortic aneurysm in whom preoperative acute renal failure was reversed with hemodialysis, aortic replacement, and renal revascularization. Prompt cerebrospinal fluid drainage reversed delayed-onset postoperative paraplegia and led to immediate, complete neurologic recovery.


Espresso Coffee Mitigates the Aggregation and Condensation of Alzheimer's Associated Tau Protein.
Espresso coffee is among the most consumed beverages in the world. Recent studies report a protective activity of the coffee beverage against neurodegenerative disorders such as Alzheimer's disease. Alzheimer's disease belongs to a group of disorders, called tauopathies, which are characterized by the intraneuronal accumulation of the microtubule-associated protein tau in fibrillar aggregates. In this work, we characterized by NMR the molecular composition of the espresso coffee extract and identified its main components. We then demonstrated with in vitro and in cell experiments that the whole coffee extract, caffeine, and genistein have biological properties in preventing aggregation, condensation, and seeding activity of the repeat region of tau. We also identified a set of coffee compounds capable of binding to preformed tau fibrils. These results add insights into the neuroprotective potential of espresso coffee and suggest candidate molecular scaffolds for designing therapies targeting monomeric or fibrillized forms of tau.


[Effects of CD/5-FC suicide gene therapy system on human malignant glioma cells in vitro].
To investigate the killing effects of cytosine deaminase/5-fluorocytosine (CD/5-FC) suicide gene therapy system on human malignant glioma cells in vitro. The pCMVCD plasmid was transfected into the U251 human malignant glioma cells using Lipofectamine 2000-mediated method. Resistant clones (named U251/CD cells) were isolated by screening with G418 presence. U251/CD cells were incubated with 5-FC in different concentrations to determine the number of viability cells (or cytotoxicity assay), and measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The concentrations of 5-fluorouracil (5-FU) in the media were measured by the high-performance liquid chromatography (HPLC) analysis. The untreated U251 cells were insensitive to 5-FC, with the IC50 about 6 500 micromol/L. After the transfection, the IC50 was dramatically reduced to about 10 micromol/L. Therefore, gene transfection made G418-resistant clones (U251/CD cells) highly sensitive to 5-FC. HPLC analysis showed that 5-FU was detected in U251/CD cell medium. The killing effects of U251 cells modified by CD gene were induced by 5-FC, and the CD/5-FC system was feasible to treat glioma.


Lymphocytes produce IL-1beta in response to Fcgamma receptor cross-linking: effects on parenchymal cell IL-8 release.
Neutrophils mediate tissue injury in response to immune complexes, although the factors that induce their recruitment are incompletely understood. We have reported that lymphocytes may be important regulators of monocyte and macrophage IL-8 release in the presence of immobilized IgG. Since tissue parenchymal cells are important local producers of IL-8 but are not directly stimulated by FcgammaR cross-linking, we hypothesized that lymphocytes may also regulate parenchymal IL-8 release. Supernatants from lymphocytes incubated on immobilized IgG induced primary human fibroblasts and human mesangial cells to produce IL-8 (17 +/- 3.5 and 44 +/- 8 ng/ml, respectively). Fibroblast and mesangial cell IL-8 mRNA levels were similarly increased by the conditioned lymphocyte supernatant. Immobilized anti-human FcgammaRIII, but not FcgammaRI or FcgammaRII Abs, could stimulate this IL-8-inducing activity in lymphocytes, suggesting that FcgammaRIII-bearing lymphocytes were responsible. Supernatants from lymphocytes incubated on immobilized IgG contained 2.2 +/- 0.8 ng/ml of IL-1beta, while enriched monocyte preparations from the same donors incubated on immobilized IgG released only 0.1 +/- 0.04 ng/ml of IL-1beta (p = 0.05). Consistent with the identification of IL-1beta as the lymphocyte factor, fibroblast or mesangial cell IL-8 release induced by the IgG-stimulated lymphocyte supernatants was inhibited by 1) the combination of IL-1R antagonist and soluble type II IL-1R, 2) an IL-1-converting enzyme inhibitor, or 3) anti-IL-1beta but not preimmune Abs. These data suggest that targeted deposits of IgG can stimulate FcgammaRIII-bearing lymphocytes to produce IL-1beta, which induces parenchymal cell IL-8 release.


YAP nuclear translocation induced by HIF-1α prevents DNA damage under hypoxic conditions.
Maladaptive repair of acute kidney injury (AKI) is associated with a high risk of developing chronic kidney disease deemed irremediable even in present days. When AKI arises from ischemia-reperfusion injury, hypoxia usually plays a major role. Although both hypoxia-inducible factor-1α (HIF-1α) and yes-associated protein (YAP) have been proven to promote renal cell survival under hypoxia, there is a lack of research that studies the crosstalk of the two and its effect on kidney repair. In studying the crosstalk, CoCl2 was used to create a mimetic hypoxic environment. Immunoprecipitation and proximity ligation assays were performed to verify protein interactions. The results show that HIF-1α interacts with YAP and promotes nuclear translocation of YAP at a high cell density under hypoxic conditions, suggesting HIF-1α serves as a direct carrier that enables YAP nuclear translocation. This is the first study to identify HIF-1α as a crucial pathway for YAP nuclear translocation under hypoxic conditions. Once translocated into a nucleus, YAP protects cells from DNA damage and apoptosis under hypoxic conditions. Since it is unlikely for YAP to translocate into a nucleus without HIF-1α, any treatment that fosters the crosstalk between the two holds the potential to improve cell recovery from hypoxic insults.


[The use of acupuncture reflex therapy in the combined treatment of osteoarthrosis patients].
As many as 40 patients with osteoarthrosis of the hip and knee joints were followed up. Of these, 20 subjects received non-steroidal anti-inflammatory drugs together with intraarticular administration of glucocorticosteroids and inhibitors of proteases. The other 20 patients were exposed, apart from the above measures, to acupuncture treatments. Indicators of articular pains and tenderness of joints in palpation got significantly lower by the end of the course of treatment in those patients having received, in addition to drugs, acupuncture treatments.


INDICATORS OF DENTAL HEALTH AND LOCAL IMMUNITY IN YOUNG ADULTS WHO HAVE SUFFERED FROM CORONAVIRUS INFECTION.
The aim: To determine the dental status and state of local immunity in young adults who have suffered from the coronavirus disease. Materials and methods: The main group consisted of 30 people aged 20-22 years, who suffered from the coronavirus infection Covid19 6.1±1.2 months ago. The comparison group included 20 people who did not have a coronavirus infection. The control group consisted of 35 people, randomized by age and sex, who did not have signs of caries and periodontal tissue disease and did not have coronavirus disease. All patients were examined for dental status and local immunity. Results: The analysis of indicators of dental status revealed the possibility of the existence of a relationship between the signs of acute SARS-Cov2 viral infection and the development of caries and periodontal tissue diseases. Significant changes in the local immunity of the oral cavity were found in the examined patients, which had a pathogenetic influence on the development and progression of caries and periodontal tissue diseases: a significant increase in the level of Ig G, as well as a probable decrease in the concentration of SIg A relative to the comparison group, a probably higher normative value of pathogenic small- and medium-molecular CICs with a significant decrease in the level of physiological large-sized CICs relative to the comparison group, a decrease in the content of anti-inflammatory IL-4, as well as increased concentration of pro-inflammatory cytokines. Conclusions: Young adults who have suffered a coronavirus infection during the last 6 months have significantly higher caries prevalence, bleeding index, PMA index and hygiene index, halitosis, which indicates deeper tissue damage and tooth pathology with the formation of dentition defects than in the comparison group. Indicators of local immunity of the oral fluid have a deep and specific character.


Soy product intake and serum isoflavonoid and estradiol concentrations in relation to bone mineral density in postmenopausal Japanese women.
To evaluate soy intake and serum concentrations of estradiol and isoflavonoids and their relationship to bone mineral density (BMD) and serum bone-specific alkaline phosphatase (bone ALP) activity, we conducted a cross-sectional study of 87 postmenopausal Japanese women. Soy product and isoflavone intake from soy products and intake of nutrients were assessed with a semiquantitative food-frequency questionnaire. BMD (mg/cm2) was measured by single-energy X-ray absorptiometry at the site of the calcaneus. Serum estradiol (E2) and the sex hormone-binding globulin (SHBG) were measured by radioimmunoassay. Serum genistein and daidzein concentrations were measured by a high-performance liquid chromatography MS/MS method. A statistically significant correlation was observed between the ratio of E2 to SHBG and BMD (Spearman r=0.38, p=0.0003) after controlling for age, body mass index, smoking status, age at menarche, and intake of vegetable fat, vitamin C and salt. Soy product and isoflavone intake and serum isoflavones were not significantly correlated with BMD after controlling for the covariates. Serum ALP was not significantly correlated with soy product and isoflavone intake, the E2/SHBG ratio or serum isoflavones. The present study supports the association of BMD with serum estradiol; however, it does not support the association of BMD with soy or isoflavone intake or serum isoflavone levels.


<Original Article>Brain activity in patients with unilateral sensorineural hearing loss during auditory perception in noisy environments.
Patients with unilateral sensorineural hearing loss (UHL) often complain of hearing difficulties in noisy environments. To clarify this, we compared brain activation in patients with UHL with that of healthy participants during speech perception in a noisy environment, using functional magnetic resonance imaging (fMRI). A pure tone of 1 kHz, or 14 monosyllabic speech sounds at 65‒70 dB accompanied by MRI scan noise at 75 dB, were presented to both ears for 1 second each and participants were instructed to press a button when they could hear the pure tone or speech sound. Based on the activation areas of healthy participants, the primary auditory cortex, the anterior auditory association areas, and the posterior auditory association areas were set as regions of interest (ROI). In each of these regions, we compared brain activity between healthy participants and patients with UHL. The results revealed that patients with right-side UHL showed different brain activity in the right posterior auditory area during perception of pure tones versus monosyllables. Clinically, left-side and right-side UHL are not presently differentiated and are similarly diagnosed and treated; however, the results of this study suggest that a lateralityspecific treatment should be chosen.


Retrospective comparison of low molecular weight heparin vs. warfarin vs. oral Xa inhibitors for the prevention of recurrent venous thromboembolism in oncology patients: The Re-CLOT study.
Background There is increasing evidence indicating oral factor Xa inhibitors can be used for secondary prevention of venous thromboembolism. Studies are needed to compare oral factor Xa inhibitors, low molecular weight heparins, and warfarin in the oncology population. The purpose of this study is to evaluate the recurrent venous thromboembolism incidence in oncology patients utilizing oral Xa inhibitors, low molecular weight heparins, or warfarin. Methods Using retrospectively collected data, we compared the recurrent venous thromboembolism incidence in oncology patients taking rivaroxaban/apixaban, enoxaparin, or warfarin with at least three months of follow-up. Patients were included if they had an active cancer, venous thromboembolism, and taking warfarin, enoxaparin, or rivaroxaban/apixaban. The primary endpoint was the first episode of recurrent venous thromboembolism at three months. Secondary endpoints included recurrent venous thromboembolism after six months, major bleeding, and mortality. Results Of 127 venous thromboembolism patients, 48 received rivaroxaban or apixaban, 23 received enoxaparin, and 56 received warfarin. The three most common cancer diagnoses were lung (21%), colorectal (14%), and breast (14%). There was no difference in venous thromboembolism recurrence at three months between the rivaroxaban/apixaban (0%), warfarin (3.6%), and the enoxaparin cohorts (4.4%) (p = 0.8319). Major bleeding at three months was only seen in one patient in the enoxaparin arm (4.2%). Mortality at three months was 0%, 3.6%, and 17.4% in the rivaroxaban/apixaban, warfarin, and enoxaparin cohorts, respectively. Conclusion The results of this retrospective study suggest that oral factor Xa inhibitors are potential options for cancer patients with venous thromboembolism. However, randomized, controlled trials are needed to confirm these results.


Determination of lithium-ion distributions in nanostructured block polymer electrolyte thin films by X-ray photoelectron spectroscopy depth profiling.
X-ray photoelectron spectroscopy (XPS) depth profiling with C60(+) sputtering was used to resolve the lithium-ion distribution in the nanometer-scale domain structures of block polymer electrolyte thin films. The electrolytes of interest are mixtures of lithium trifluoromethanesulfonate and lamellar-forming polystyrene-poly(oligo(oxyethylene)methacrylate) (PS-POEM) copolymer. XPS depth profiling results showed that the lithium-ion concentration was directly correlated with the POEM concentration. Furthermore, chemical state and atomic composition of the film were analyzed through the deconvolution of the C1s signal, indicating that the lithium ions appear to be uniformly distributed in the POEM domains. Overall, the unique capabilities of C60(+) depth profiling XPS provide a powerful tool for the analysis of nanostructured polymer thin films in applications ranging from energy storage and generation to surface coatings and nanoscale templates.


[Variation trends of China terrestrial vegetation net primary productivity and its responses to climate factors in 1982-2000].
A new estimation model of vegetation net primary production (NPP) based on remote sensing data and climatic data was presented, with which, the NPP of China terrestrial vegetation in 1982-2000 was estimated, and the intra- and inter- annual variation patterns of the NPP and its responses to climate factors were studied. The results showed that there was an obvious seasonal regularity in the intra-annual variation of the NPP. In 1982-2000, all the terrestrial vegetation types presented an increasing annual NPP, with the greatest increment for deciduous needle leaf forests and the smallest one for grasses. Evergreen broadleaf forests had the largest inter-annual variation, while grasses had the smallest one. Comparing with temperature, precipitation played a stronger driving role in the intra-annual variation of the NPP, and the effects of precipitation and temperature were more obvious in North China than in South China. The driving roles of the climate factors varied with season and latitude.


Diagnostic utility of array-based comparative genomic hybridization in a clinical setting.
Array-based comparative genomic hybridization is a recently introduced technique for the detection of submicroscopic genomic imbalances (deletions or duplications) across the entire genome. To assess the potential utility of a widely available array-based comparative genomic hybridization platform that targets specific, clinically relevant, loci across the genome for cytogenetic diagnosis in a clinical setting, we reviewed the medical records of all 373 patients at Children's Hospital Boston who had normal chromosomal analysis and were tested with this targeted array-based comparative genomic hybridization over a 1-year period from November 1, 2004 to October 31, 2005. These patients were tested because of a suspicion of chromosomal abnormalities based on their clinical presentation. Thirty-six patients (9.7%) had abnormal array-based comparative genomic hybridization results. Twenty patients (5.4%) had potentially pathogenetic genomic imbalances and 16 patients (4.3%) had copy number variations that are not believed to be pathogenetic. Thirteen of 234 patients (5.6%) with mental retardation/global developmental delay, 10/114 patients (8.8%) with facial dysmorphism, 5/58 patients (8.6%) with multiple congenital anomalies, and 4/35 patients (11.4%) with both facial dysmorphism and multiple congenital anomalies had potentially pathogenetic genomic imbalances. Targeted array-based comparative genomic hybridization is a clinically available test that is useful in the evaluation of patients suspected of having chromosomal disorders. However, it is best used as an adjunct to chromosomal analysis when a clear genetic diagnosis is unavailable.


Venous lesions as a cause of sylvian aqueductal obstruction: case report.
The cases of two patients who presented with sylvian aqueductal obstruction caused by venous lesions (an ectatic vein and a developmental venous anomaly, which are uncommon causes of obstructive hydrocephalus) are reported. A 42-year-old man presented with chronic headache and behavior abnormalities. Magnetic resonance imaging revealed supratentorial ventricular dilation caused by an obstruction of the sylvian aqueduct by a developmental venous anomaly. An 18-year-old man complained of intermittent headaches. The magnetic resonance imaging scan disclosed aqueductal stenosis-type hydrocephalus secondary to an ectatic vein. Both patients underwent endoscopic third ventriculostomy and recovered well. During the procedures, the aqueductal obstruction by venous elements could be seen clearly. Venous anomalies may cause obstructive hydrocephalus and can be suspected in cases of chronic and intermittent headaches. Endoscopic third ventriculostomy is an effective treatment.


Design, synthesis, and in vitro anti-hepatocellular carcinoma of novel thymine thioglycoside analogs as new antimetabolic agents.
A first reported direct method for preparation of thymine thioglycoside analogs utilizing novel pyrimidine-2(1H)-thiones and α-bromoglucose or α-bromogalactose tetraacetate as starting components is described. The synthetic potential of the method is demonstrated. The evaluation of antiproliferative activity against HepG-2 cell lines (Liver carcinoma cell lines) shows that most of the compounds have high antitumor activities especially 6b, 6e, 11b, and 12b. Moreover, molecular modelings of these compounds reveal that they have high binding affinity through hydrogen bond interaction with the binding pocket of thymidylate synthase dihydrofolate reductase (TS-DHFR).


Nanoscale chemical imaging of the additive effects on the interfaces of high-voltage LiCoO2 composite electrodes.
X-ray photoemission electron microscopy (X-PEEM) of cycled LiCoO2 composite electrodes has revealed the interfaces of various components within the composite electrodes and their dependence on additives in the electrolyte and the interplay of multiple components in the electrodes. This study visualizes CoF2 distribution and Co-O bonding variation along with local component agglomeration and degradation. The obtained new insights will assist further development of long-life high-voltage LiCoO2/C batteries.


Management of fetal lung lesions.
We have learned from prenatal diagnosis that there is a wide spectrum of clinical severity for fetuses that have a lung mass. Accurate prognostic information is necessary for providing appropriate management and parental counseling. If an associated life-threatening anomaly is present or if the mother is ill with the mirror syndrome, then the family might choose to terminate the pregnancy. If the fetus is not hydropic and an isolated fetal lung lesion is present, the mother is followed by serial ultrasound and arrangements are made for the best possible care after birth. Some CCAMs and many BPSs will shrink in size, so it is important to try to differentiate these lesions using prenatal diagnostic criteria, although this technique is not always possible. All fetuses that had fetal thoracic masses without hydrops in our series survived in the setting of maternal transport, planned delivery, and postnatal evaluation at a facility with ECMO capability. Many of the babies that had large lesions at our center required ventilatory support, and six babies needed treatment with ECMO. Our impression is that these nonhydropic fetuses that had lung masses had less lung hypoplasia and a much better prognosis than those that had diaphragmatic hernia despite a similar degree of mediastinal shift as judged by prenatal sonography. In asymptomatic neonates that have a cystic lung lesion, we believe that elective resection is warranted because of the risks of infection and occult malignant transformation. Malignancies consist mainly of pleuropulmonary blastoma in infants and young children and bronchioloalveolar carcinoma in older children and adults. After confirmation of CCAM location by postnatal chest CT scan with intravenous contrast, we recommend elective resection at 1 month of age or older. This age has been chosen because anesthetic risk in babies decreases after 4 weeks of age. An experienced pediatric surgeon can safely perform a lobectomy in infants with minimal morbidity. Early resection also maximizes compensatory lung growth. In contrast, we have usually followed patients with a tiny, asymptomatic, noncystic BPS if we are confident of the diagnosis based on postnatal imaging studies. We do not favor the approach of catheterization and embolization for the treatment of larger BPS lesions. If the fetus is hydropic at presentation or if hydrops develops during serial follow-up, management depends upon the gestational age. For hydropic fetuses of greater than 32 weeks' gestation, early delivery should be considered so that the lesion can be resected ex utero, but the neonatal outcome is dismal. We recently managed two such cases using an ex utero intrapartum therapy (EXIT) strategy with resection of the mass during the EXIT procedure. Both fetuses survived and one required the use of ECMO. For hydropic fetuses of less than 32 weeks' gestation, there is now a new therapeutic option, treating the lesion before birth.


The SKN-1 hunger games: May the odds be ever in your favor.
Animals must continually assess nutrient availability to develop appropriate strategies for survival and reproductive success. It is no secret that nutritional state plays a large role in both aging and health.(1-7) Appropriate cellular energy usage is not only crucial for animal starvation survival, but is also important for diseases such as obesity and cancer, which characteristically have metabolic dysfunction.(8-10) C. elegans are exceptionally well poised to handle bouts of starvation as resource availability in the wild varies greatly.(11,12) We recently discovered an evolutionarily conserved pathway, regulated by the cytoprotective transcription factor SKN-1/Nrf2, which integrates diet composition and availability with utilization for survival.(13,14) These responses have potent impact on organismal physiology and remarkably are influenced by current and parental life history events, including choice of diet. In this commentary we will focus on recent insights concerning dietary intake and the impact that this can have throughout the life history of the nematode, Caenorhabditis elegans. In light of the strong impact that diet plays throughout life we urge caution when interpreting previous studies that make use of only one diet and suggest a reinvestigation utilizing a different diet is warranted.


Familial anaplastic ependymoma: evidence of loss of chromosome 22 in tumour cells.
A family with anaplastic ependymomas, histologically verified in three cases and neuroradiologically suggested in a fourth, is presented. Two healthy brothers both had two affected sons. All four male patients were younger than 5 years at the time of diagnosis. Two boys died before the age of 3 years. Genotype analysis (with polymorphic DNA markers for chromosome 22 and interphase cytogenetic analysis) of one of the tumours showed a subpopulation of tumour cells with monosomy of (part of) chromosome 22. Non-neoplastic cells of this patient showed a normal karyotype. These findings give further evidence for the role of a tumour suppressor gene on chromosome 22 in the pathogenesis of familial ependymal tumours.


Equine viral vaccines: the past, present and future.
The increasing international movement of horses combined with the relaxation of veterinary regulations has resulted in an increased incidence of equine infectious diseases. Vaccination, along with management measures, has become the primary method for the effective control of these diseases. Traditionally modified live and inactivated vaccines have been used and these vaccines have proven to be very successful in preventing disease. However, there are a number of equine infectious diseases for which conventional technology has shown its limitations. The advent of recombinant technology has stimulated the development of second generation vaccines, including gene deleted mutants, live vectored vaccines and DNA vaccines. These vaccines have in common that protective antigens are endogenously processed and presented along the molecules of the MHC I and MHC II complex, resulting in the stimulation of both humoral and cell-mediated immune responses similar to natural infection. The present paper provides a review of the vaccines being employed today against the most important equine viral diseases followed by a summary of new developments that are expected to bring improved vaccines to the market in the foreseeable future.


[Clinical analysis on tuberculosis cases among foreigners in our hospital].
Although the incidence rate in Japan has been decreasing since the declaration of tuberculosis emergency in 1999, the reported tuberculosis cases among foreigners have been increasing year by year (from 5.1% in 2000 to 6% in 2003). As the number of foreign residents in Japan has been increasing every year, tuberculosis cases among them are also expected to increase. The aim of this study is to investigate and clarify clinical features of recent tuberculosis patients among foreigners. Fifty-two cases were analyzed, who were admitted to our hospital because of active tuberculosis from January 2004 to April 2007. Among total 52 cases, male was 29, female 23, and the mean age (SD) of the patients was 31.8 (+/- 8.8) years old. Their mother countries were China, Republic of Korea and so on. The cavitary lesions were found on chest X-ray in 54%, the drug resistant rate was 8.2%, and the treatment completion rate was 92%. Comparing with reports in the past, almost parameters about tuberculosis control have improved, for example the drug resistant rate was decreased and the treatment completion rate was increased. The promotion of DOTS strategy in Japan might be attributed to the improvement of these parameters. Because more immigrants from the developing countries are expected in near future, not only strengthening current DOTS strategy but also new countermeasures such as QFT-2G and Electronic-Nose Technology should be introduced into tuberculosis control of foreigners living in Japan to decrease tuberculosis incidence and improve treatment outcome by early detection and adherence to treatment.


Clinical implications of defining the gross tumor volume with combination of CT and 18FDG-positron emission tomography in non-small-cell lung cancer.
To compare the planning target volume (PTV) definitions for computed tomography (CT) vs. positron emission tomography (PET) in non-small-cell lung cancer (NSCLC). A total of 21 patients with NSCLC underwent three-dimensional conformal radiotherapy planning. All underwent a staging F-18 fluorodeoxyglucose-position emission tomography (18FDG-PET) scan and underwent treatment simulation using CT plus a separate planning 18FDG-PET scan. Three sets of target volumes were defined: Set 1, CT volumes (CT tumor + staging PET nodal disease); Set 2, PET volumes (planning PET tumor {gross tumor volume (GTV) = [(0.3069 x mean standardized uptake value) + 0.5853])}; Set 3, composite CT-PET volumes (fused CT-PET tumor). Sets 1 and 2 were compared using a matching index. Three-dimensional conformal radiotherapy plans were created using the Set 1 (CT) volumes; and coverage of the Set 3 (composite) volumes was evaluated. Separate three-dimensional conformal radiotherapy plans were designed for the Set 3 volumes. For the primary tumor GTV, the Set 1 (CT) volume was larger than the Set 2 (PET) volume in 48%, smaller in 33%, and equal in 19%. The mean matching index was 0.65 (35% CT-PET mismatch). Although quantitatively similar, the volumes differed qualitatively. The Set 3 (composite) volume was larger than either CT or PET alone in 62%, smaller in 24%, and equal in 14%. The dose-volume histogram parameters did not differ among the plans for Set 1 (CT) vs. Set 3 (composite) volumes. Small portions of the Set 3 PTV were significantly underdosed in 40% of cases using the CT-only plan. Computed tomography and PET are complementary and should be obtained in the treatment position and fused to define the GTV for NSCLC. Although the quantitative absolute target volume is sometimes similar, the qualitative target locations can be substantially different, leading to underdosage of the target when planning is done using CT alone without PET fusion.


Acute pancreatitis after viperid snake cerastes cerastes envenoming: a case report.
Snakebites by the viper snake Cerastes cerastes are quite common across the world but rarely published with regard to their mostly benign course. The reported case study depicts the envenoming of a 36-year-old Czech man, a private herpetologist, who suffered snakebite to his finger. He developed a painful local reaction with hemorrhagic oedema. Subsequently, consumption coagulopathy with thrombocytopenia and haemolysis, colicky pain in the epigastrium and acute renal failure developed. Acute exudative pancreatitis was diagnosed on the third day after envenoming. Hemorrhagic oedema of the arm was complicated by a phlegmon. Symptomatic treatment including haemodialysis, fresh frozen plasma and thrombocytes was administered. Antivenom was not administered due to the delay in referral to the specialized unit. The patient recovered within one month, only postnecrotic defects of the finger persisted.


Community partnerships: educational linkages to increase the number of primary care practitioners.
The Community Partnerships initiative is focused on the creation of academic, non-hospital community health centers shaped by people and institutions at the local level. In our view, public policy-makers need such positive ideas and programs to support--things to be for rather than against. Incessant lamenting about the problems of the health care system will change the system less than will positive programs shaped and supported by the people whose needs they serve. All of us in medical education recognize the need for change in medical education. The Community Partnerships program represents one strategy for change that brings communities directly into the sphere of influence and enables them to enhance the relevance of the educational experience for health professions students.


Occupational class differences in outcomes after ischemic stroke: a prospective observational study.
Occupational class is an integral part of socioeconomic status. The studies focused on the occupational difference in ischemic stroke outcome in a Chinese population are limited. We aimed to investigate the associations between occupational class and the prognosis of patients with ischemic stroke in China. We included 1484 ischemic stroke participants (mean age: 63.42 ± 11.26 years) from the prospective cohort study: Infectious Factors, Inflammatory Markers and Prognosis of Acute Ischemic Stroke (IIPAIS). Occupational class was categorized into white-collar workers, blue-collar workers and farmers in our study. Study outcomes were cardiovascular events and all-cause mortality within 12 months after ischemic stroke onset. We applied Cox proportional hazard model to evaluate the associations between the occupational class and study outcomes after ischemic stroke. Within 12 months after ischemic stroke, there were 106 (7.5%) cardiovascular events and 69 (4.9%) all-cause deaths. The Kaplan-Meier plots showed that white-collar workers had highest risk of cardiovascular events after 12-month follow-up (Log-rank P = 0.02). Multivariate adjusted hazard ratio and 95% confidence intervals (CIs) of farmers versus white-collar workers was 0.43(0.20-0.91) for cardiovascular events. No significant difference showed in blue-collar workers versus white-collar workers, with fully adjusted hazard ratio 0.62(95% CIs, 0.23-1.67). Compared with white-collar workers, farmers are associated with less risk of cardiovascular events at 12 months after ischemic stroke, while there are no significant differences in blue-collar workers.


An evaluation of local item dependencies in the Medical Council of Canada Qualifying Examination Part I.
This study investigates (a) whether items within the Multiple-Choice Questions component of the Medical Council of Canada's Qualifying Examination Part I exhibit local dependencies and (b) potential sources of such dependencies. The dimensionality of each of six discipline-based subtests was assessed based on exploratory nonlinear factor analyses. A standardized Fisher's z statistic was used to test residual item correlations for local item dependencies. The characteristics of pairs of items flagged as possibly locally dependent were reviewed. Some items in the Pediatrics and Public Medicine/Community Health subtests are locally dependent; these tend to be the more difficult items on the subtests. While these results are encouraging, the possible causes and potential impacts of any local dependencies should be investigated further.