Subjective assessment of rehabilitation protocol by patients after ACL reconstruction - preliminary report.
Subjective evaluation by patients has recently become an important adjunct to postoperative clinical assessment. Apart from standard physical examination, scales demonstrating patients' subjective outcome measures are used for assessing the efficacy of the treatment and rehabilitation of knee ligamentous injuries. The present work presents patients' subjective assessment of rehabilitation protocols after ACL reconstruction. Forty individuals who had undergone ACL reconstruction were randomised into two groups (G1, G2) and followed one of two rehabilitation protocols (A or B). The subjects assessed their knee function at baseline and after physical therapy using the Lysholm score and the IKDC form. The results were analysed with the Mann-Whitney U test. The subjects also completed a questionnaire at discharge. Analysis of Lysholm and IKDC scores revealed significant differences between the mean pre- and postrehabilitation results in the groups (p<0.05). The greatest improvement was seen in G2 patients rehabilitated with protocol B, with significant mean improvements of 56.3% and 46.7% for the Lysholm and IKDC scores, respectively. Group G1 registered only half of this magnitude of change. Protocol B was also highly rated in the questionnaires. According the patients opinion a rehabilitation protocol involving a larger number of open kinetic chain exercises may prove more effective in the rehabilitation of patients after ACL reconstruction compared to a programme basing mainly on closed kinetic chains.


Neurofibromatosis type 2 protein co-localizes with elements of the cytoskeleton.
The product of the neurofibromatosis type 2 (NF2) tumor suppressor gene is a 595-amino-acid protein bearing resemblance to a family of band-4.1-related proteins. These proteins, including ezrin, radixin, and moesin, probably function as molecular linking proteins, connecting the cytoskeleton to the cell membrane. On the grounds of the homology to the ezrin, radixin, and moesin proteins and on the basis of its predicted secondary structure, the NF2 protein is also thought to act as a cytoskeleton-cell membrane linking protein. Using monoclonal antibodies to amino- and carboxyl-terminal synthetic NF2 peptides we demonstrate the co-localization of the NF2 protein with elements of the cytoskeleton in a COS cell model system and in cultured human cells. Furthermore, the presence of the NF2 protein in tissue sections is shown. The monoclonal antibodies specifically stain smooth muscle cells and the stratum granulosum of the human epidermis. In cultured smooth muscle cells the NF2 protein co-localizes with actin stress fibers. Immunoelectron microscopy demonstrates the presence of the NF2 protein associated with keratohyalin granules and to a lesser extent with intermediate filaments in the human epidermis. We conclude that the NF2 protein is indeed associated with multiple elements of the cytoskeleton.


Dacron vs vein for femoropopliteal arterial bypass. Should the saphenous vein be spared?
The increasing need for the saphenous vein to bypass lesions of the coronary and other small arteries prompts a reconsideration of its routine use for femoropopliteal bypass. Evaluation after five years in 124 consecutive patients (135 procedures) demonstrated no significant difference in overall definitive patency between venous grafts (63%) and Dacron prostheses (65%). Dacron prostheses were avoided when below-knee anastomoses were required, but when the distal anastomoses were made above the knee, the five-year patency for veins and Dacron was equal (67%). Although the quality of the distal runoff influenced the long-term patency, effects were similar for veins and for Dacron. The data support the use of Dacron prostheses for femoropopliteal bypass proximal to the knee joint, allowing preservation of the saphenous vein for possible use elsewhere.


Metabolic syndrome components can predict C reactive protein concentration in adolescents.
Metabolic syndrome (MS) is suggested to be associated with a low grade inflammation state, but the relationship between inflammation biomarkers and the components of metabolic syndrome in adolescents are still lacking. To investigate the association between C-reactive protein (CRP) serum concentrations and metabolic syndrome components in adolescents. A cross-sectional population based study was conducted. Anthropometric, biochemical and clinical data were collected from 524 adolescents (11-15 years old) randomly sampled from school population of Alegre city, Espírito Santo, Brazil. Data were analyzed by STATA version 9.0. Adolescents with higher values for BMI (p = 0.001) and higher body fat percentage (p = 0.003) had higher CRP concentrations than those with lower BMI and body fat percentage. CRP concentrations was directly correlated with BMI (r = 0.17, p = 0.0001), waist circumference (r = 0.15, p = 0.0005), HDL-c (r = 0.13, p = 0.003), fasting insulin (r = 0.12, p = 0.003) and systolic blood pressure (r = 0.11, p with = 0.01). In the multiple linear regression analysis BMI (r = 0.05, p = 0.002), fasting glucose (r = -0.01, p = 0.003) and HDL-c (r = 0.017, p < 0.001) were associated to CRP concentrations after adjusting for the other components of MS. The association found between individual components of MS and CRP concentrations suggests that inflammation might be an early event in the development of metabolic disorders in adolescents.


The analgesic effect of a vapocoolant stream spray in reducing heat nociception on the glabrous skin of rat pups.
Blood sampling is a common screening and diagnostic test in newborn infants in the neonatal intensive care unit, and heel lancing accounts for two-thirds of these tests. Heel lancing causes acute pain and distress, and most infants rarely receive analgesics because of fear of respiratory depression from opioids and lack of effectiveness of topical local anesthetics on the glabrous skin. To circumvent this latter problem, we investigated the analgesic efficacy and safety of a topical vapocoolant spray. Forty Sprague-Dawley rat pups aged 7 days old were randomly assigned to receive either vapocoolant or saline spray on the plantar hindpaws for 5 to 6 seconds. Forty-five seconds later, the paws were subjected to a modified hotplate test to quantify the nociceptive flexor withdrawal (NFW) thresholds before and after treatment with the sprays. Seven days later, the animals were euthanized and the hindpaws were examined histologically. A nested analysis of variance approach was used to account for the triplicate measurements per animal. A 2-tailed P < 0.05 was considered significant. At baseline, there were no differences in the NFW thresholds between the 2 groups (P = 0.22). After treatment, these thresholds were significantly lower in both vapocoolant (P < 0.001) and saline (P = 0.008) groups relative to baseline values. The vapocoolant group demonstrated a significantly longer NFW latency time compared to the saline group (P < 0.001). All specimens in both groups were examined and showed normal skin histology. Vapocoolant spray treatment of the glabrous skin is effective and safe after a single treatment.


A combined analysis of regional energy metabolism and immunohistochemical ischemic damage in the gerbil brain.
By combining immunohistochemical technique with microassay methods, we analyzed regional energy metabolism in vulnerable and tolerant areas of gerbil brains during evolution of neuronal damage after bilateral common carotid artery occlusion for 10 min with subsequent reperfusion. Four animals were used for each reperfusion period. Based on the information from the immunohistochemical examination, we dissected out vulnerable and tolerant subregions of the hippocampus, cerebral cortex, and thalamus from freeze-dried 20-microm-thick sections, and measured the levels of creatine phosphate (P-Cr), adenine nucleotides, guanine nucleotides, and purine bodies by HPLC, and the levels of glucose, glycogen, and lactate by an enzyme-immobilized column method. There were no significant differences in the levels of metabolites between vulnerable and tolerant subregions of control brains. After reperfusion, both vulnerable and tolerant subregions recovered preischemic metabolic profiles by 2 days. Although the regional differences between vulnerable and tolerant subregions were minimal at each reperfusion period, there were delays in the recovery of P-Cr, ATP, and/or total adenine nucleotides in all vulnerable subregions. A decline of P-Cr, ATP, and GTP levels without change in %ATP, AMP, or purine bodies occurred after reperfusion for 3 days, coinciding with the development of immunohistochemical damage by the immunoreaction for microtubule-associated protein 1A. The results supported the notion that subtle but sustained impairment of energy metabolism caused by mitochondrial dysfunction in the early reperfusion period might trigger delayed neuronal death in vulnerable subregions.


Caged AG10: new tools for spatially predefined mitochondrial uncoupling.
The study of mitochondria and mitochondrial Ca2+ signalling in localised regions is hampered by the lack of tools that can uncouple the mitochondrial membrane potential (DeltaPsi(m)) in a spatially predefined manner. Although there are a number of existing mitochondrial uncouplers, these compounds are necessarily membrane permeant and therefore exert their actions in a spatially unselective manner. Herein, we report the synthesis of the first caged (photolabile protected) mitochondrial uncouplers, based on the tyrphostin AG10. We have analysed the laser photolysis of these compounds, using (1)H NMR and HPLC, and demonstrate that the major product of caged AG10 photolysis is AG10. It is shown that photolysis within single smooth muscle cells causes a collapse of DeltaPsi(m) consistent with photorelease of AG10. Furthermore, the effect of the photoreleased AG10 is localised to a subcellular region proximal to the site of photolysis, demonstrating for the first time spatially predefined mitochondrial uncoupling.


[Physiologic and pathologic role of iron in the human body. Iron deficiency anemia in newborn babies].
Iron is one of the most important essential metal ions of which significance is well known for ages. This element is a key moiety of several enzymes in iron containing heme or nonheme form and transfer and storage protein, hemoglobin and myoglobin. Several membrane carriers of iron have already been identified. The redox state of iron is determined by xanthine oxidase, cytochromes and Hp or ceruloplasmin and ferroxidase activity of apo-ferritin, respectively. Some vitamins (C, B2-, B3-, B6-, B12) play also a role in the metabolism of iron. The iron content of cells of the organs is well regulated by the iron homeostasis. Iron has a significant role in the immune system by producing oxygen containing free radicals. Anaemia induced by iron deficiency may cause a challenge concerns for pregnant women, babies and adolescent, primarily.


Feasibility evaluation of a new pericardial bioprosthesis with dye mediated photo-oxidized bovine pericardial tissue.
In an attempt to overcome the problem of calcification of bioprostheses, a novel bovine pericardial tissue valve preserved with a non-aldehyde, dye mediated photo-oxidation process (PhotoFixTM) developed by CarboMedics, Inc. The device was evaluated by implantation in the mitral position of juvenile sheep with a mean age of 3.5 months. Thirteen valves were evaluated; six experimental valves with photo-oxidized tissue, five identically designed valves with glutaraldehyde-fixed tissue, and two Carpentier-Edwards pericardial valves as controls. Four of the six animals in the photo-oxidized group were free of calcification when electively sacrificed at 152 days, 152 days, one year and 1.5 years respectively. One animal was electively sacrificed at 98 days. Pathologic findings indicated minimal calcification of the valve due to uneven stress distribution from two bent stent posts that most likely occurred during surgical implantation, but the device was still functional. The sixth animal with photo-oxidized tissue died at 131 days due to massive calcification of a single leaflet. There was no pathologic evidence of infection. Explants at five months from additional and still continuing sheep studies per FDA guidelines have not reproduced single leaflet calcification in over forty explanted valves with photo-oxidized tissue. The glutaraldehyde-fixed valves all exhibited some calcification at explant; two of these animals died early due to the mineralization. Both control animals with Carpentier-Edwards valves died early from mitral stenosis due to extensive device calcification. The fact that four of six valves with photo-oxidized tissue remained free of any signs of calcification for up to 1.5 years, while none of the other valves did, suggests that photo-oxidation is a promising method of preserving and fixing tissue for use in bioprostheses. These results suggest that photo-oxidized bioprosthetic valves may be clinically valuable and warrant further study.


[Non-conditional logistic regression analysis on risk factors of central venous catheter-related infection].
To study the correlation of indwelling central venous catheter and systemic infection, to study the causative microorganisms and factors contributing to infections, and the diagnosis and treatment of such infection. All the central venous catheters were produced by American or German companies. Subclavian vein, internal jugular vein, or femoral vein was chosen. Skin swab, blood in the catheter and peripheral blood were cultured. Clinical data including sex, age, disease, times of puncture, site of puncture, indwelling duration, type of catheter, caliber of catheter (single or double chamber, hemodialysis), nursing care, ways of use of the catheter were recorded, and they were subjected to non-conditional logistic regression analysis, then independent risk factors were determined with multivariate stepwise non-conditional logistic regression analysis. Unvaried non-conditional logistic regression analysis showed that sex, primary disease, site of puncture, nursing care, and ways of use of the catheter showed no correlation with CRS. Multivariate stepwise non-conditional logistic regression analysis showed that indwelling duration [odds ratio (OR)=2.682, 95% confidence interval (CI): 1.156-6.226, chi2=5.275, P=0.022], caliber of catheter (OR=2.702, 95% CI: 1.183-6.175, chi2=5.559, P=0.018) and white blood cell count (WBC)<4x10(9)/L (OR=1.371, 95% CI:1.044-1.800, chi2=5.142, P=0.023) were independent factors. The clinical study of 1,100 patients showed that the total correlated infection rate was 2.5% (28/1,100). Central venous catheterization is the major cause of bacteremia in hospital. The risk factors of infection are maintenance duration, location, and individual difference, and they are obviously correlated.


Partial dynamical symmetry in quantum Hamiltonians with higher-order terms.
A generic procedure is proposed to construct many-body quantum Hamiltonians with partial dynamical symmetry. It is based on a tensor decomposition of the Hamiltonian and allows the construction of a hierarchy of interactions that have selected classes of solvable states. The method is illustrated in the SO(6) limit of the interacting boson model of atomic nuclei and applied to the nucleus 196Pt.


Metastatic Colon Cancer in the Pituitary: A Case Report with Review of Literature.
We report a rare case of metastatic colonic adenocarcinoma to the pituitary gland in a 58-year-old who presented with visual decline and panhypopituitarism. He underwent urgent transsphenoidal endoscopic surgery with significant improvement of his vision, followed by adjuvant fractionated radiotherapy to the resection cavity. He made a satisfactory recovery, but regrettably died from COVID-19 9 weeks after completion of radiotherapy. A multidisciplinary approach is essential for optimal management of this condition due to its rarity and complexity.


Molecular basis for activation of G protein-coupled receptor kinases.
G protein-coupled receptor (GPCR) kinases (GRKs) selectively recognize and are allosterically regulated by activated GPCRs, but the molecular basis for this interaction is not understood. Herein, we report crystal structures of GRK6 in which regions known to be critical for receptor phosphorylation have coalesced to stabilize the kinase domain in a closed state and to form a likely receptor docking site. The crux of this docking site is an extended N-terminal helix that bridges the large and small lobes of the kinase domain and lies adjacent to a basic surface of the protein proposed to bind anionic phospholipids. Mutation of exposed, hydrophobic residues in the N-terminal helix selectively inhibits receptor, but not peptide phosphorylation, suggesting that these residues interact directly with GPCRs. Our structural and biochemical results thus provide an explanation for how receptor recognition, phospholipid binding, and kinase activation are intimately coupled in GRKs.


Influence of endodontic materials on the bonding of glass ionomer cement to dentin.
We assessed the bond strength of a glass ionomer cement to dentin that had been in contact with different materials. Flat dentin surfaces in freshly extracted human teeth were covered for 48 h with a 1 mm layer of a variety of materials that are used for temporary filling or root canal sealing. The products were mechanically removed and a glass ionomer cement cylindrical specimen bonded to the dentin surface. After 7-days immersion in 37 degrees C water the tensile bond strength was tested. The results were compared with those on dentin surfaces not in contact with any endodontic material. The statistical analysis showed that none of the materials used interfered with the bonding of the glass ionomer to dentin.


[Rapid reduction of a variety of organic functionalities including a new selective reduction with samarium diiodide].
This review deals with the rapid reduction of a variety of organic functionalities, including a new selective reduction of carboxylic acid, with samarium diiodide in the presence of additives under mild conditions. The single electron donor ability of samarium diiodide can be enhanced with ligands around Sm2+ when sufficient electrons are supplied from the ligands. Mechanistic consideration of this enhancement led to our finding that carboxylic acid, ester, amide, nitrile, pyridine and other functionalities were rapidly reduced with samarium diiodide in the presence of a base, acid, water and methanol as ligands at room temperature in good yields. Particularly, these systems directly reduced carboxylic acid into alcohol and a samarium diiodide--85% phosphoric acid system immediately reduced an aromatic primary amide to aldehyde in good yield. Pyridines were reduced to piperidines with a samarium diiodide-base or water system in excellent yields; also, the aromatic nucleus of phenol derivatives was rapidly reduced with a samarium diiodide-base system. Furthermore, these organic functionalities were rapidly reduced with an Sm or Yb metal-hydrochloric acid system. Aliphatic and aromatic carboxylic acids with a coexisting aldehyde or that bearing a formyl group were selectively reduced to the corresponding alcohols with a new samarium diiodide-samarium triflate-methanol-base or water system within a few minutes at room temperature in good to almost quantitative yield.


Expression profiling of metalloproteinases and their inhibitors in cartilage.
To profile the expression of all known members of the matrix metalloproteinase (MMP), ADAMTS, and tissue inhibitor of metalloproteinases (TIMP) gene families in normal cartilage and cartilage from patients with osteoarthritis (OA). Human cartilage was obtained from femoral heads at joint replacement for OA or following fracture to the femoral neck. Total RNA was purified, and gene expression was assayed using quantitative real-time polymerase chain reaction. Several members of the above gene families were regulated in OA. Genes that showed increased expression in OA were MMP13, MMP28, and ADAMTS16 (all at P < 0.001), MMP9, MMP16, ADAMTS2, and ADAMTS14 (all at P < 0.01), and MMP2, TIMP3, and ADAMTS12 (all at P < 0.05). Genes with decreased expression in OA were MMP1, MMP3, and ADAMTS1 (all at P < 0.001), MMP10, TIMP1, and ADAMTS9 (all at P < 0.01), and TIMP4, ADAMTS5, and ADAMTS15 (all at P < 0.05). Correlation analysis revealed that groups of genes across the gene families were coexpressed in cartilage. This is the first comprehensive expression profile of all known MMP, ADAMTS, and TIMP genes in cartilage. Elucidation of patterns of expression provides a foundation with which to understand mechanisms of gene regulation in OA and potentially to refine the specificity of antiproteolytic therapies.


Activation of P2X(7)-mediated apoptosis Inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice.
The study tested the hypothesis that apoptosis can prevent and control growth of neoplastic cells. Previous studies in-vitro have shown that the pro-apoptotic P2X(7) receptor regulates growth of epithelial cells. The specific objective of the present study was to understand to what degree the P2X(7) system controls development and growth of skin cancer in vivo, and what cellular and molecular mechanisms are involved in the P2X(7) action. Skin neoplasias in mice (papillomas, followed by squamous spindle-cell carcinomas) were induced by local application of DMBA/TPA. Experiments in-vitro utilized cultured epidermal keratinocytes generated from wild-type or from P2X(7)-null mice. Assays involved protein immunostaining and Western blots; mRNA real-time qPCR; and apoptosis (evaluated in situ by TUNEL and quantified in cultured keratinocytes as solubilized DNA or by ELISA). Changes in cytosolic calcium or in ethidium bromide influx (P2X(7) pore formation) were determined by confocal laser microscopy. (a) Co-application on the skin of the P2X7 specific agonist BzATP inhibited formation of DMBA/TPA-induced skin papillomas and carcinomas. At the completion of study (week 28) the proportion of living animals with cancers in the DMBA/TPA group was 100% compared to 43% in the DMBA/TPA+BzATP group. (b) In the normal skin BzATP affected mainly P2X(7)-receptor - expressing proliferating keratinocytes, where it augmented apoptosis without evoking inflammatory changes. (c) In BzATP-treated mice the degree of apoptosis was lesser in cancer than in normal or papilloma keratinocytes. (d) Levels of P2X(7) receptor, protein and mRNA were 4-5 fold lower in cancer tissues than in normal mouse tissues. (e) In cultured mouse keratinocytes BzATP induced apoptosis, formation of pores in the plasma membrane, and facilitated prolonged calcium influx. (f) The BzATP-induced apoptosis, pore-formation and augmented calcium influx had similar dose-dependence for BzATP. (g) Pore formation and the augmented calcium influx were depended on the expression of the P2X(7) receptor, while the BzATP-induced apoptosis depended on calcium influx. (h) The BzATP-induced apoptosis could be blocked by co-treatment with inhibitors of caspase-9 and caspase-3, but not of caspase-8. (a) P2X(7)-dependent apoptosis is an important mechanism that controls the development and progression of epidermal neoplasia in the mouse. (b) The P2X(7)-dependent apoptosis is mediated by calcium influx via P2X(7) pores, and involves the caspase-9 (mitochondrial) pathway. (c) The diminished pro-apoptotic effect of BzATP in mouse cancer keratinocytes is possibly the result of low expression of the P2X(7) receptor. (d) Activation of P2X(7)-dependent apoptosis, e.g. with BzATP could be a novel chemotherapeutic growth-preventive modality for papillomas and epithelial cancers in vivo.


Self-Rated Depressive Symptoms in Children and Youth with and without Cerebral Palsy: A Pilot Study.
Children with cerebral palsy (CP) often exhibit mental health problems, such as depressive symptoms. The purpose of this study was to describe the self-rated depressive symptoms in children with and without CP and to investigate the associated predictors. Participants included 24 children with CP and 33 typically developing (TD) children. Depressive symptoms were assessed using the Birleson Depression Self-Rating Scale for Children. Parents of the participants completed the Strengths and Difficulties Questionnaire. Severity of self-rated depressive symptoms was higher in children with CP than that in TD children. Particularly, decline in activities and enjoyment was identified as a contributor to the increased severity of depressive symptoms. Hierarchical multiple regression analysis revealed that the greater severity of depressive symptoms in children with CP was mediated by hyperactivity/inattention and peer problems. Our study suggests that it is imperative to provide opportunities to participate in social activities from an early age.


Reentrant Phase Transitions and Non-Equilibrium Dynamics in Membraneless Organelles.
Compartmentalization of biochemical components, interactions, and reactions is critical for the function of cells. While intracellular partitioning of molecules via membranes has been extensively studied, there has been an expanding focus in recent years on the critical cellular roles and biophysical mechanisms of action of membraneless organelles (MLOs) such as the nucleolus. In this context, a substantial body of recent work has demonstrated that liquid-liquid phase separation plays a key role in MLO formation. However, less is known about MLO dissociation, with phosphorylation being the primary mechanism demonstrated thus far. In this Perspective, we focus on another mechanism for MLO dissociation that has been described in recent work, namely a reentrant phase transition (RPT). This concept, which emerges from the polymer physics field, provides a mechanistic basis for both formation and dissolution of MLOs by monotonic tuning of RNA concentration, which is an outcome of cellular processes such as transcription. Furthermore, the RPT model also predicts the formation of dynamic substructures (vacuoles) of the kind that have been observed in cellular MLOs. We end with a discussion of future directions in terms of open questions and methods that can be used to answer them, including further exploration of RPTs in vitro, in cells, and in vivo using ensemble and single-molecule methods as well as theory and computation. We anticipate that continued studies will further illuminate the important roles of reentrant phase transitions and associated non-equilibrium dynamics in the spatial patterning of the biochemistry and biology of the cell.


Racial/Ethnic disparities in the awareness, treatment, and control of hypertension - United States, 2003-2010.
Hypertension is a leading cause of cardiovascular disease and affects nearly one third of U.S. adults. Because the risk for cardiovascular disease mortality increases as blood pressure increases, clinical recommendations for persons with stage 2 hypertension (systolic blood pressure [SBP] ≥160 mmHg or diastolic blood pressure [DBP] ≥100 mmHg) include a more extensive treatment and follow-up regime than for those with stage 1 hypertension (SBP 140-159 mmHg or DBP 90-99 mmHg). Although racial/ethnic disparities in the prevalence of hypertension have been well documented; ethnic disparities in the awareness, treatment, and control within blood pressure stages have not. To examine racial/ethnic disparities in awareness, treatment, and control of high blood pressure by hypertension stages, CDC analyzed data from the National Health and Nutrition Examination Survey (NHANES) for the period 2003-2010. This report describes the results of that analysis, which indicated that the proportion of Mexican-Americans and blacks with stage 1 and stage 2 hypertension was greater than for whites.* Among those with stage 1 hypertension, treatment with medication was significantly lower for Mexican-Americans compared with their non-Hispanic counterparts. Although treatment among persons with stage 2 hypertension did not differ by race/ethnicity, less than 60% of those with stage 2 hypertension were treated with medication. More efforts are needed to reduce barriers to accessing health care and low-cost medication, as well as increasing clinicians' hypertension treatment knowledge and adherence to clinical guidelines.


Microarray and bioinformatics analysis of gene expression in experimental membranous nephropathy.
Passive Heymann nephritis (PHN), the best characterized animal model of experimental membranous nephropathy, is characterized by subepithelial immune deposits, podocyte foot processes effacement and massive proteinuria beginning 4 days following disease induction. Although single genes involved in PHN have been studied, no whole genome-wide expression analysis of kidney tissue has been performed. Microarray analysis was performed to identify gene expression changes in PHN rat kidneys during the onset of proteinuria. Our results showed that 234 transcripts were differentially expressed in diseased animals compared to controls. Genes exclusively upregulated in diseased animals were mainly required for cell structure and motility, immunity and defense, cell cycle, and developmental processes. The single most increased gene was transgelin (Tagln) showing a 70-fold upregulation in animals with PHN. Protein-protein interaction analysis revealed the following four processes of major relevance in disease manifestation: (i) DNA damage and repair; (ii) changes in the extracellular matrix; (iii) deregulation of cytokines and growth factors, as well as (iv) rearrangements of the cytoskeleton. We show for the first time the complex interplay between multiple different genes in experimental membranous nephropathy, supporting a role for genomic approaches to better understanding and defining specific disease processes.


Electrophysiological characterization of the modified hERGT potassium channel used to obtain the first cryo-EM hERG structure.
The voltage-gated hERG (human-Ether-à-go-go Related Gene) K+ channel plays a fundamental role in cardiac action potential repolarization. Loss-of-function mutations or pharmacological inhibition of hERG leads to long QT syndrome, whilst gain-of-function mutations lead to short QT syndrome. A recent open channel cryo-EM structure of hERG represents a significant advance in the ability to interrogate hERG channel structure-function. In order to suppress protein aggregation, a truncated channel construct of hERG (hERGT ) was used to obtain this structure. In hERGT cytoplasmic domain residues 141 to 350 and 871 to 1,005 were removed from the full-length channel protein. There are limited data on the electrophysiological properties of hERGT channels. Therefore, this study was undertaken to determine how hERGT influences channel function at physiological temperature. Whole-cell measurements of hERG current (IhERG ) were made at 37°C from HEK 293 cells expressing wild-type (WT) or hERGT channels. With a standard +20 mV activating command protocol, neither end-pulse nor tail IhERG density significantly differed between WT and hERGT . However, the IhERG deactivation rate was significantly slower for hERGT . Half-maximal activation voltage (V0.5 ) was positively shifted for hERGT by ~+8 mV (p < .05 versus WT), without significant change to the activation relation slope factor. Neither the voltage dependence of inactivation, nor time course of development of inactivation significantly differed between WT and hERGT , but recovery of IhERG from inactivation was accelerated for hERGT (p < .05 versus WT). Steady-state "window" current was positively shifted for hERGT with a modest increase in the window current peak. Under action potential (AP) voltage clamp, hERGT IhERG showed modestly increased current throughout the AP plateau phase with a significant increase in current integral during the AP. The observed consequences for hERGT IhERG of deletion of the two cytoplasmic regions may reflect changes to electrostatic interactions influencing the voltage sensor domain.


The carboxyl terminal amino acid residues of Pseudomonas aeruginosa exotoxin A involved in cell toxicity and pathogenesis, characterized by a neutralizing human monoclonal antibody.
Human monoclonal antibody HI-1A4 (IgG3, lambda) neutralized a toxicity caused by pseudomonal exotoxin A (Ex-A) in cell culture and in vivo, and was effective in experimental Pseudomonas aeruginosa infections in mice. HI-1A4 inhibited an Ex-A catalyzed ADP-ribosylation of elongation factor 2 but did not inhibit an incorporation of toxin into a target cell at all. One molecule of HI-1A4 neutralized at least 2 molecules of Ex-A. HI-1A4 retained its binding activity at pH 4.0. The epitope region for HI-1A4 was demonstrated to be a carboxyl terminal end of amino acid residues 591-613 of Ex-A. HI-1A4 might bind to Ex-A carboxyl terminal region outside a target cell, be incorporated into cells as a complex with Ex-A, and inhibit the intracellular function in which the carboxyl terminal part of Ex-A was involved, resulting in the interruption of intoxication of Ex-A.


Transfer of neuroplasticity from nucleus accumbens core to shell is required for cocaine reward.
It is well established that cocaine induces an increase of dendritic spines density in some brain regions. However, few studies have addressed the role of this neuroplastic changes in cocaine rewarding effects and have often led to contradictory results. So, we hypothesized that using a rigorous time- and subject-matched protocol would demonstrate the role of this spine increase in cocaine reward. We designed our experiments such as the same animals (rats) were used for spine analysis and behavioral studies. Cocaine rewarding effects were assessed with the conditioned place preference paradigm. Spines densities were measured in the two subdivisions of the nucleus accumbens (NAcc), core and shell. We showed a correlation between the increase of spine density in NAcc core and shell and cocaine rewarding effects. Interestingly, when cocaine was administered in home cages, spine density was increase in NAcc core only. With anisomycin, a protein synthesis inhibitor, injected in the core we blocked spine increase in core and shell and also cocaine rewarding effects. Strikingly, whereas injection of this inhibitor in the shell immediately after conditioning had no effect on neuroplasticity or behavior, its injection 4 hours after conditioning was able to block neuroplasticity in shell only and cocaine-induced place preference. Thus, it clearly appears that the neuronal plasticity in the NAcc core is essential to induce plasticity in the shell, necessary for cocaine reward. Altogether, our data revealed a new mechanism in the NAcc functioning where a neuroplasticity transfer occurred from core to shell.


Infantile flexural seborrhoeic dermatitis. Neither biotin nor essential fatty acid deficiency.
The allegedly beneficial effect of biotin in the treatment of infantile 'flexural' seborrhoeic dermatitis was evaluated in a double-blind controlled study. No beneficial effect could be confirmed, and it is therefore unlikely that this disease is caused by biotin deficiency. Nor could this scaly dermatitis be ascribed to an essential fatty acid deficiency. Serum and adipose tissue fatty acids resembled each other and reflected the fatty acid composition of the diet.


The cephalogastric phase of the pancreatic response to food in the dog.
We studied post-meal pancreatic secretion and gastrin release in conscious dogs with duodenal Thomas cannulas. Normal dogs were tested in physiological conditions and with an i.v. infusion of atropine 20 micrograms/kg/h or secretin 0.5 CU/kg/h. The responses were also studied after antral and truncal vagotomy. In the early phase (0-20 min) of the response, before gastric emptying started, antral vagotomy reduced fluid and protein outputs, and truncal vagotomy reduced them still more. Atropine reduced only the protein response. Gastrin release reached a peak after 20-25 min. After antral and truncal vagotomy, gastrin release was reduced within 10 min after the meal. Late-phase (greater than 20 min) pancreatic secretion depended on the presence of chyme in the duodenum. The effects of atropine and antral vagotomy in the cephalogastric phase could be explained by antropancreatic reflexes stimulating fluid secretion (atropine-resistant pathway) and protein output (atropine-sensitive pathway).


Biodegradable magnesium wire promotes regeneration of compressed sciatic nerves.
Magnesium (Mg) wire has been shown to be biodegradable and have anti-inflammatory properties. It can induce Schwann cells to secrete nerve growth factor and promote the regeneration of nerve axons after central nervous system injury. We hypothesized that biodegradable Mg wire may enhance compressed peripheral nerve regeneration. A rat acute sciatic nerve compression model was made, and AZ31 Mg wire (3 mm diameter; 8 mm length) bridged at both ends of the nerve. Our results demonstrate that sciatic functional index, nerve growth factor, p75 neurotrophin receptor, and tyrosine receptor kinase A mRNA expression are increased by Mg wire in Mg model. The numbers of cross section nerve fibers and regenerating axons were also increased. Sciatic nerve function was improved and the myelinated axon number was increased in injured sciatic nerve following Mg treatment. Immunofluorescence histopathology showed that there were increased vigorous axonal regeneration and myelin sheath coverage in injured sciatic nerve after Mg treatment. Our findings confirm that biodegradable Mg wire can promote the regeneration of acute compressed sciatic nerves.


A New Propolis Type from Changbai Mountains in North-east China: Chemical Composition, Botanical Origin and Biological Activity.
Propolis is a bee product with a wide range of biological activities and its chemical compounds depend highly on the type of plant accessible to the bees. The Changbai Mountains are a major mountain range in Northeast China and are one of the major bee product-producing areas in China. In this study, we evaluated the total phenolic acids and flavonoid contents as well as the antioxidant activity of propolis sampled from the Changbai Mountains area (CBM). We identified the major compounds and qualified their contents by HPLC-ESI/MS and HPLC-UV, and found that the content of p-coumaric acid and an unknown peak (CBE) in CBM propolis was higher than in propolis from other parts of China. The unknown compound CBE was isolated, purified, and identified as benzyl p-coumarate by MS and NMR. Possible plant sources of CBM propolis are Populus davidiana dode and Populus simonii Carr, which widely distributed in the Changbai Mountains area. CBM propolis is a new propolis type, that could be an excellent raw material for health foods and pharmaceuticals.


Decreased GFAP-mRNA expression in spinal cord of cobalamin-deficient rats.
We have demonstrated previously that chronic vitamin B12 [cobalamin (Cbl)] deficiency preferentially affects glial cells in the rat central nervous system (CNS) and severely affects peripheral glial cells independently of and concomitantly with the central neuropathy. In this study, we determined the mRNA levels for myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in different CNS areas of rats made Cbl-deficient by total gastrectomy, as well as the mRNA levels for glycoprotein Po and peripheral myelin protein (PMP)22 in the sciatic nerve. GFAP-mRNA levels were significantly decreased in the spinal cord (SC) and hypothalamus, but not in the cortex, hippocampus, or striatum of totally gastrectomized (TGX) rats. No differences in GFAP protein levels were found in the SC and hypothalamus of the TGX rats treated or not with Cbl. MBP-mRNA levels were significantly decreased only in the hypothalamus, and the levels of mRNA for both glial markers returned to normal with Cbl replacement therapy. The levels of mRNA for the various myelin proteins in the sciatic nerve were not modified by Cbl deficiency. These results demonstrate that: a) the neurotrophic action of Cbl in rat CNS occurs in a zonal manner; and b) Cbl deficiency does not affect myelin synthesis (with the sole exception of the hypothalamus).


Altering the Specificity of the Antibody Response to HIV gp120 with a Glycoconjugate Antigen.
Some conserved glycans on the HIV envelope protein are targets of broadly neutralizing antibodies (bnAbs) of HIV. BnAbs provide a precise definition of broadly neutralizing epitopes on the envelope protein of HIV. These epitopes are promising for vaccine design. Many glycan-related antigens with high affinity to bnAbs have been tested as immunogens in vivo. However, it was found that no bnAb-like antibodies were induced. Vaccination with different immunogens containing the same neutralizing epitope may enhance the affinity maturation of antibodies which focus on the shared epitope. This combined immunization strategy showed great potential in peptide epitope-based vaccine design. However, it has not yet been explored on glycan-related epitopes to date. Herein, we take 2G12 as a model to validate this strategy on glycan-related epitopes. A high-affinity antigen of 2G12 was constructed by conjugating the D1 arm tetramannoside to bovine serum albumin. Then, the glycoconjugate was coimmunized with a recombinant gp120, which was expected to selectively benefit the induction of antibodies recognizing the neutralizing epitope of 2G12 on gp120. Mice were inoculated with the two antigens simultaneously or alternately to determine the suitable regimen for this strategy. The serological assays demonstrated that the antibody titers and subtypes responded to the whole gp120 were not improved, and the proportion of antibodies competitively bound to the 2G12 epitope was not enhanced significantly either. However, the coimmunized glycoconjugate selectively raised the proportion of antibodies recognizing D1 arm tetramannoside-related structures on gp120. These results provide important experience for the design of glycan-dependent bnAb-based vaccines.


[Respiratory function impairment during treatment of chronic hepatitis C with peginterferon alfa2 and ribavirin. Two cases presentation].
Pulmonary complications during standard therapy of chronic hepatitis C with pegylated interferon and ribavirin are rare but connected with wide spectrum of diseases from sarcoidosis to interstitial pneumonitis. The clinical course of that complications is often serious. In this paper, presentation of two patients with chronic hepatitis C with different anamnesis was shown. In the first case, without pulmonary burden, during therapy the features of pneumonitis were developed. In the second case, in patient with sarcoidosis, the antiviral therapy was carried out without important pulmonary aggravation. In reference to these observations and based on available literature, the pathogenetic mechanisms underlying pulmonary complications during this kind of therapy were discussed. Additionally, the scheme of pulmonary diagnostic proceeding in patients certified and then treated with peginterferon and ribawirin was proposed.


Aggressive Ossifying Fibroma of the Maxilla.
The aggressive ossifying fibroma is an uncommon benign fibro-osseous lesion which has been described in the literature under a variety of terms. This tumor is distinguished from standard ossifying fibroma based on its more clinically aggressive biological behavior, occurrence in children and young adults, and tendency to occur in different anatomic sites. We report a case of a 45-year-old female who presented with a unilateral swelling of the right middle face for 5 months. Clinical examination showed a mass extended over the right maxilla. Orthopantomogram and computed tomography scan were performed. Biopsy suggests a fibro-osseous lesion. The complete surgical excision of tumor was performed under local anesthesia. The histopathological examination revealed the diagnosis of an aggressive ossifying fibroma-trabeculae type. No recurrence was noted. Because of its aggressive and compressive nature, aggressive ossifying fibroma requires an early complete surgical excision. A long-term clinical and radiological surveillance is necessary to prevent recurrence.


Cold ischemia does not interfere with tolerance induction.
Ischemia/reperfusion injury activates innate immunity, which in turn may prevent tolerance induction. We asked whether prolonged cold ischemia interferes with successful tolerance induction. Kidneys from Dark Agouti donors were grafted into binephrectomized Lewis rats after short (20 min) or prolonged (6 hr) cold ischemia. Tolerance was induced by nondepleting anti-CD4 monoclonal antibody RIB 5/2 (10 mg/kg for 5 days). Binephrectomized untreated and cytotoxic T-lymphocyte antigen (CTLA)-4Ig treated recipients served as controls. Animals were followed for 100 days. Adoptive transfer experiments into sublethally irradiated naive Lewis were performed at day 100. Animals received kidneys from Dark Agouti rats subsequently without further immunosuppression and were followed for an additional 20 days. All RIB 5/2-treated recipients survived the first observation period independent of the cold ischemia time. Graft function, morphology, and transferred T-cell numbers were comparable in both groups. Twenty days after transfer amounts of intragraft and peripheral donor-derived cells were significantly reduced in recipients of the initially prolonged cold ischemia group associated with an attenuated immune response. Our results prove that an initially extended cold ischemia does not interfere with tolerance induced by RIB 5/2. Moreover, we conclude that a "tolerizing conditioning" achieved by prolonged cold ischemia during the tolerance-induction phase may reduce the immune response in recipients of an adoptive cell transfer.


Ectopic expression of CXCR5/BLR1 accelerates retinoic acid- and vitamin D(3)-induced monocytic differentiation of U937 cells.
The product of the blr1 gene is a CXC chemokine receptor (CXCR5) that regulates B lymphocyte migration and has been implicated in myelomonocytic differentiation. The U937 human leukemia cell line was used to study the role of blr1 in retinoic acid-regulated monocytic leukemia cell growth and differentiation. blr1 mRNA expression was induced within 12 hr by retinoic acid in U937 cells. To determine whether the early induction of blr1 might regulate inducible monocytic cell differentiation, U937 cells were stably transfected with blr1 (U937/blr1 cells). Ectopic expression of blr1 caused no significant cell cycle or differentiation changes, but caused the U937/blr1 cells to differentiate faster when treated with either retinoic acid or 1alpha,25-dihydroxyvitamin D(3). Treated with retinoic acid, U937/blr1 cells showed a greater increase in the percentage of CD11b expressing cells than vector control cells. Retinoic acid also induced a higher percentage of functionally differentiated blr1 transfectants as assessed by nitroblue tetrazolium reduction. U937/blr1 cells underwent moderate growth inhibition on treatment with retinoic acid. Similar results occurred with 1alpha,25-dihydroxyvitamin D(3). Because blr1 was induced early during cell differentiation and because its overexpression accelerated monocytic differentiation, it may be important for signals controlling cell differentiation.


Extrusion and Injection Molding of Poly(3-Hydroxybutyrate-co-3-Hydroxyhexanoate) (PHBHHx): Influence of Processing Conditions on Mechanical Properties and Microstructure.
Biobased and biodegradable polyhydroxyalkanoates (PHAs) have great potential as sustainable packaging materials. However, improvements in their processing and mechanical properties are necessary. In this work, the influence of melt processing conditions on the mechanical properties and microstructure of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) is examined using a full factorial design of experiments (DoE) approach. We have found that strict control over processing temperature, mold temperature, screw speed, and cooling time leads to highly increased elongation at break values, mainly under influence of higher mold temperatures at 80 °C. Increased elongation of the moldings is attributed to relaxation and decreased orientation of the polymer chains together with a homogeneous microstructure at slower cooling rates. Based on the statistically substantiated models to determine the optimal processing conditions and their effects on microstructure variation and mechanical properties of PHBHHx samples, we conclude that optimizing the processing of this biopolymer can improve the applicability of the material and extend its scope in the realm of flexible packaging applications.


CD8 T Cells Show Protection against Highly Pathogenic Simian Immunodeficiency Virus (SIV) after Vaccination with SIV Gene-Expressing BCG Prime and Vaccinia Virus/Sendai Virus Vector Boosts.
Toward development of a dual vaccine for human immunodeficiency virus type 1 (HIV-1) and tuberculosis infections, we developed a urease-deficient bacillus Calmette-Guérin (BCG) strain Tokyo172 (BCGΔurease) to enhance its immunogenicity. BCGΔurease expressing a simian immunodeficiency virus (SIV) Gag induced BCG antigen-specific CD4+ and CD8+ T cells more efficiently and more Gag-specific CD8+ T cells. We evaluated its protective efficacy against SIV infection in cynomolgus monkeys of Asian origin, shown to be as susceptible to infection with SIVmac251 as Indian rhesus macaques. Priming with recombinant BCG (rBCG) expressing SIV genes was followed by a boost with SIV gene-expressing LC16m8Δ vaccinia virus and a second boost with SIV Env-expressing Sendai virus. Eight weeks after the second boost, monkeys were repeatedly challenged with a low dose of SIVmac251 intrarectally. Two animals out of 6 vaccinees were protected, whereas all 7 control animals were infected without any early viral controls. In one vaccinated animal, which had the most potent CD8+ T cells in an in vitro suppression activity (ISA) assay of SIVmac239 replication, plasma viremia was undetectable throughout the follow-up period. Protection was confirmed by the lack of anamnestic antibody responses and detectable cell-associated provirus in various organs. Another monkey with a high ISA acquired a small amount of SIV, but it later became suppressed below the detection limit. Moreover, the ISA score correlated with SIV acquisition. On the other hand, any parameter relating anti-Env antibody was not correlated with the protection.IMPORTANCE Because both AIDS and tuberculosis are serious health threats in middle/low-income countries, development of a dual vaccine against them would be highly beneficial. To approach the goal, here we first assessed a urease-deficient bacillus Calmette-Guérin (BCG) for improvement of immunogenicity against both Mycobacterium tuberculosis and SIV. Second, we demonstrated the usefulness of Asian-origin cynomolgus monkeys for development of a preclinical AIDS vaccine by direct comparison with Indian rhesus macaques as the only validated hosts that identically mirror the outcomes of clinical trials, since the availability of Indian rhesus macaques is limited in countries other than the United States. Finally, we report the protective effect of a vaccination regimen comprising BCG, the highly attenuated vaccinia virus LC16m8Δ strain, and nontransmissible Sendai virus as safe vectors expressing SIV genes using repeated mucosal challenge with highly pathogenic SIVmac251. Identification of CD8+ T cells as a protective immunity suggests a future direction of AIDS vaccine development.


Interfacial Phenomena in Multi-Micro-/Nanolayered Polymer Coextrusion: A Review of Fundamental and Engineering Aspects.
The multilayer coextrusion process is known to be a reliable technique for the continuous fabrication of high-performance micro-/nanolayered polymeric products. Using laminar flow conditions to combine polymer pairs, one can produce multilayer films and composites with a large number of interfaces at the polymer-polymer boundary. Interfacial phenomena, including interlayer diffusion, interlayer reaction, interfacial instabilities, and interfacial geometrical confinement, are always present during multilayer coextrusion depending on the processed polymers. They are critical in defining the microstructural development and resulting macroscopic properties of multilayered products. This paper, therefore, presents a comprehensive review of these interfacial phenomena and illustrates systematically how these phenomena develop and influence the resulting physicochemical properties. This review will promote the understanding of interfacial evolution in the micro-/nanolayer coextrusion process while enabling the better control of the microstructure and end use properties.


The epidemiology of primary angle closure and associated glaucomatous optic neuropathy.
Angle closure glaucoma is emerging as a leading cause of blindness in the densely populated countries of Asia. It has a greater propensity to cause bilateral blindness than either primary open-angle glaucoma or secondary glaucoma. An estimated 9.4 million people in China aged 40 years and older have glaucomatous optic neuropathy. Approximately 5.2 million people (55%) would be blind in at least one eye. Around 1.7 million (18.1%) would be blind in both eyes. it is likely that PACG is responsible for the vast majority (91%) of bilateral glaucoma blindness in China. The number of Chinese people with an "occludable" drainage angle is in the region of 28.2 million, and of these 9.1 million have significant angle closure. There is a growing emphasis on a revised method of classifying the disease, which reserves the term "glaucoma" for cases with glaucomatous optic neuropathy. The term primary angle closure (PAC) is used in cases with a closed angle and peripheral anterior synechiae or raised intraocular pressure. Risk factors for PAC include older age, female gender, Chinese ethnicity, all of which are associated with anatomical risk factors of central and/or peripherally shallow anterior chambers (usually associated with a thicker, anteriorly-positioned lens), and a shorter axial length of the globe.


Roflumilast N-oxide inhibits bronchial epithelial to mesenchymal transition induced by cigarette smoke in smokers with COPD.
Epithelial to mesenchymal transition (EMT) is under discussion as a potential mechanism of small airway remodelling in COPD. In bronchial epithelium of COPD and smokers markers of EMT were described. In vitro, EMT may be reproduced by exposing well-differentiated human bronchial epithelial cells (WD-HBEC) to cigarette smoke extract (CSE). EMT may be mitigated by an increase in cellular cAMP. This study explored the effects of roflumilast N-oxide, a PDE4 inhibitor on CSE-induced EMT in WD-HBEC and in primary bronchial epithelial cells from smokers and COPD in vitro. WD-HBEC from normal donors were stimulated with CSE (2.5%) for 72 h in presence of roflumilast N-oxide (2 nM or 1 μM) or vehicle. mRNA and protein of EMT markers αSMA, vimentin, collagen-1, E-cadherin, ZO-1, KRT5 as well as NOX4 were quantified by real-time quantitative PCR or protein array, respectively. Phosphorylated and total ERK1/2 and Smad3 were assessed by protein array. cAMP and TGFβ1 were measured by ELISA. Reactive oxygen species (ROS) were determined by DCF fluorescence, after 30 min CSE (2.5%). Apoptosis was measured with Annexin V/PI labelling. In some experiments, EMT markers were determined in monolayers of bronchial epithelial cells from smokers, COPD versus controls. Roflumilast N-oxide protected from CSE-induced EMT in WD-HBEC. The PDE4 inhibitor reversed both the increase in mesenchymal and the loss in epithelial EMT markers. Roflumilast N-oxide restored the loss in cellular cAMP following CSE, reduced ROS, NOX4 expression, the increase in TGFβ1 release, phospho ERK1/2 and Smad3. The PDE4 inhibitor partly protected from the increment in apoptosis with CSE. Finally the PDE4 inhibitor decreased mesenchymal yet increased epithelial phenotype markers in HBEC of COPD and smokers. Roflumilast N-oxide may mitigate epithelial-mesenchymal transition in bronchial epithelial cells in vitro.


Long-term follow-up of metabolic activity in human alveolar echinococcosis using FDG-PET.
[(18)F]fluoro-deoxyglucose positron-emission-tomography (FDG-PET) detects metabolic activity in alveolar echinococcosis (AE). The slow changes in metabolic and morphological characteristics require long-term follow-up of patients. This is the first study to evaluate metabolic activity over may years, hereby assessing the utility of FDG-PET for the evaluation of disease progression and response to treatment. 15 patients received a follow-up FDG-PET combined with computed tomography (integrated PET/CT) with a median of 6.5 years after the first PET in 1999. Number and location of enhanced metabolic activity in the area of AE lesions was determined. Quantification of intensity of metabolic activity was assessed by calculation of mean standardized uptake values. AE lesions in 11/15 patients had been metabolically inactive initially, but only two showed permanent inactivity over the course of 81 months. Interestingly, in two patients metabolic activity was newly detected after 80 and 82 months. Benzimidazole treatment was intermittently discontinued in seven cases. Persisting activity at FDG-PET demanded continued benzimidazole treatment in four patients. Neither treatment duration, lesional size, calcifications nor regressive changes correlated with metabolic activity. Treatment responses are heterogeneous and vary from progressive disease despite treatment to long-term inactive disease with discontinued treatment. Lack of metabolic activity indicates suppressed parasite activity and is not equivalent to parasite death. However, metabolic activity may remain suppressed for years, allowing for temporary treatment discontinuation. Relapses are reliably detected with PET and restarting benzimidazole treatment prevents parasite expansion.


[Negative correlation between BMD and HbA1C in patients with type 2 diabetes].
This study included 145 patients with type 2 diabetes, and 95 non-diabetic control. We measured bone mineral density (BMD) at the sites with different cortical/cancellous bone ratio (lumbar spine, femoral neck, and distal radius). BMD and Z score at the distal radius were significantly lower in type 2 diabetic patients than those in control subjects. In type 2 diabetic patients, negative correlation between BMD and the mean HbA(1C) during the last 2 years was found significantly at the distal radius in both sexes. These results indicate the selective cortical bone loss in type 2 diabetes, and suggest the importance of evaluating BMD at the radius as well and keeping good metabolic control to prevent bone loss in type 2 diabetic patients.


Assessing treatment effect in pancreatic cancer.
Pancreatic cancer is one of the most deadly forms of cancer (43,140 new cases per year; 36,800 deaths), and most people with pancreatic cancer do not survive past 5 years. New therapeutic regimens are constantly being evaluated in an attempt to reduce the rapid progression of this disease. Although some patients receive neoadjuvant therapy in an attempt to make a nonresectable or borderline-resectable tumor resectable, more patients with resectable disease are being enrolled in clinical trials that provide neoadjuvant therapy. This means more pancreatic resections must be evaluated for therapy effect. Histologic grading schemes for the assessment of posttherapy response have been described, but difficulties associated with determining the histologic features of treatment effect in pancreatic cancer have not been addressed. To critically review the diagnostic criteria for proposed grading schemes for pancreatic cancer treated with neoadjuvant chemoradiation therapy and to provide guidance to surgical pathologists who encounter treated pancreatic cancer resections. Published peer-reviewed literature and the personal experience of the authors. Assessment of treatment effect in pancreatic cancer is difficult. Pathologists need to be aware that some histologic features of treatment effect overlap with histologic features seen in untreated pancreatic cancer, such as tumor cell anaplasia, necrosis, and fibrosis. Careful assessment of pancreatic resections, including detailed gross examination and thorough histologic sampling, is important in accurately assessing treatment effect and improving patient outcomes.


Breastfeeding Duration and Development of Dysglycemia in Women Who Had Gestational Diabetes Mellitus: Evidence from the GUSTO Cohort Study.
(1) Background: Breastfeeding has been shown to support glucose homeostasis in women after a pregnancy complicated by gestational diabetes mellitus (GDM) and is potentially effective at reducing long-term diabetes risk. (2) Methods: Data from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study were analyzed to understand the influence of breastfeeding duration on long-term dysglycemia (prediabetes and diabetes) risk in women who had GDM in the index pregnancy. GDM and dysglycemia four to seven years postpartum were determined by the oral glucose tolerance test (OGTT). A Poisson regression model with a robust error variance was used to estimate incidence rate ratios (IRRs) for dysglycemia four to seven years post-delivery according to groupings of the duration of any breastfeeding (<1, ≥1 to <6, and ≥6 months). (3) Results: Women who had GDM during the index pregnancy and complete breastfeeding information and OGTT four to seven years postpartum were included in this study (n = 116). Fifty-one women (44%) had postpartum dysglycemia. Unadjusted IRRs showed an inverse association between dysglycemia risk and ≥1 month to <6 months (IRR 0.91; 95% confidence interval [CI] 0.57, 1.43; p = 0.68) and ≥6 months (IRR 0.50; 95% CI 0.27, 0.91; p = 0.02) breastfeeding compared to <1 month of any breastfeeding. After adjusting for key confounders, the IRR for the ≥6 months group remained significant (IRR 0.42; 95% CI 0.22, 0.80; p = 0.008). (4) Conclusions: Our results suggest that any breastfeeding of six months or longer may reduce long-term dysglycemia risk in women with a history of GDM in an Asian setting. Breastfeeding has benefits for mothers beyond weight loss, particularly for those with GDM.


[Comparison of deficits in visual cortex between anisometropic and strabismic amblyopia by fMRI retinotopic mapping].
To study the neural mechanism of visual cortical deficits between anisometropic and strabismic amblyopia comparatively by BOLD-fMRI retinotopic mapping. Ten anisometropic amblyopes, 10 strabismic amblyopes and 9 normal subjects underwent fMRI with retinotopic mapping and luminous spots stimuli (spatial frequency: 6 cpd, contrast: 0.5). 1.5T MRI system was used to obtain functional images of visual cortex. Responses in primary and secondary visual cortex were compared among the dominant (normal subject group), anisometropic and strabismic amblyopic eyes by one-way ANOVA, successively analyzed by paired-samples t test between amblyopic eyes and fellow fixing eyes (anisometropic and strabismic amblyopia group respectively). Their fMRI deficits of amblyopes were analyzed regressively in two amblyopia groups respectively. The result of one-way ANOVA showed significantly a lower activation (average T value) in V1, V2, V3, Vp and V7 visual areas (P < 0.05, P values 0.018, 0.007, 0.002, 0.000, 0.025 respectively) between anisometropic amblyopia and normal group. This was in accordance with the result of paired-samples t test between amblyopic eyes and fellow fixing eyes in anisometropic amblyopia group (P < 0.05, P values 0.035, 0.007, 0.020, 0.009, 0.023 respectively). Statistical difference was found in V1, V2 and Vp areas between strabismic amblyopia and normal group (P < 0.05, P values 0.010, 0.007 & 0.003 respectively). The paired-samples t test in strabismic amblyopia group showed statistical difference only in V2, Vp areas (P < 0.05, P values 0.026 and 0. 009 respectively. ). So the two results were discordant. Between the two amblyopic groups, there was no statistical difference (P > 0.05) except in V7 area (P < 0.05, P value = 0.048). There was no causal relation between the primary visual cortical deficits and the secondary cortex in amblyopia (P > 0.05). Anisometropic amblyopia and strabismic amblyopia both have functional deficits in the primary and secondary visual cortex. The neural mechanism of secondary visual cortical deficits may be more complex than decreased cortex activation induced by the deficit of primary cortex. In the primary cortex, strabismic amblyopia and anisometropic amblyopia have neuronal deficits and/or abnormal interaction. In addition, strabismic amblyopia may also have suppressive influences of the fixing eyes upon the amblyopic eyes. Anisometropic amblyopia has the neural undersampling at a high spatial frequency in the secondary visual cortex as compared to amblyopic amblyopia.


[CME: Paraneoplastic Endocrine Syndromes].
CME: Paraneoplastic Endocrine Syndromes Abstract. Paraneoplastic endocrine syndromes are caused by ectopic hormone production by malignant tumor cells. Knowledge of paraneoplastic endocrine syndromes may allow a timely diagnosis of the underlying cancer at a treatable stage and, on the other hand, appropriate treatment of the endocrine manifestations reduces morbidity and mortality of the affected patients. The most common endocrine syndromes are paraneoplastic hypercalcaemia, caused by the secretion of PTHrP, and hyponatremia, caused by the inadequate secretion of ADH. Although there may be clinical symptoms like fatigue, nausea/vomiting and renal insufficiency for hypercalcaemia and gait disturbances and mental alterations for hyponatremia, the diagnosis must be confirmed by laboratory testing and prompt the search for associated tumors.


Use of the Oximeter-539 WTW, equipped with a sensor Trioxmatic-300, for the functional analysis of dilute solutions of human Hb-A.
Dissociation curves for oxygen of dilute samples of human adult Hb-A were evaluated on this occasion, by using the Oximeter-539 WTW with its sensor, and a suitable spectrophotometer. At this purpose, Hb samples were desaturated in oxygen upon given experimental conditions, by bubbling pure nitrogen in them, and their re-oxigenation in air was followed, step by step, by multiple oximetries. In addition, all the spectrophotometric measurements of the saturation of Hb-O2%, corresponding to each individual oximetry, were carried out parallely but separately. Dilution of Hb-A was maintained at 0.1 mM in heme. The p50 at pH 7.3 was 4.435 +/- 0.299 Torr, with the n-value of 2.7 +/- 0.2; Bohr effect was -0.55 +/- 0.08, within a pH range between 6.8, 7.3 and 7.8, whereas chloride and DPG effects at pH 7.3 (the most useful value) were 0.42 +/- 0.44 and 0.453 +/- 0.0187 respectively. In conclusion, these results are similar to those obtained with automated procedures, upon comparable experimental conditions, but do not require expensive and sophisticated instruments. Such a technique could be very useful in the hemoglobinopathies, which are common in Italy, and it could be easily adapted to perform comparative studies on animal hemoglobins not far from human species.


In Vivo Translatome Profiling in Spinal Muscular Atrophy Reveals a Role for SMN Protein in Ribosome Biology.
Genetic alterations impacting ubiquitously expressed proteins involved in RNA metabolism often result in neurodegenerative conditions, with increasing evidence suggesting that translation defects can contribute to disease. Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, whose role in pathogenesis remains unclear. Here, we identified in vivo and in vitro translation defects that are cell autonomous and SMN dependent. By determining in parallel the in vivo transcriptome and translatome in SMA mice, we observed a robust decrease in translation efficiency arising during early stages of disease. We provide a catalogue of RNAs with altered translation efficiency, identifying ribosome biology and translation as central processes affected by SMN depletion. This was further supported by a decrease in the number of ribosomes in SMA motor neurons in vivo. Overall, our findings suggest ribosome biology as an important, yet largely overlooked, factor in motor neuron degeneration.


Stereoselective Self-Assembly of Complex Chiral Radial [5]Catenanes Using Half-Sandwich Rhodium/Iridium Building Blocks.
Herein, we have successfully achieved the stereoselective synthesis of two chiral radial [5]catenanes in a single step through the self-assembly of bidentate ligands containing l-alanine residues and binuclear half-sandwich organometallic rhodium(III)/iridium(III) clips. Remarkably, these two chiral radial [5]catenanes exhibit complex stereochemical structures as revealed by single-crystal X-ray diffraction. The eight binuclear units and eight bidentate ligands in their solid-state structures all exhibit a single planar chirality, and the interlocking between molecular macrocycles exhibits a single co-conformational mechanical helical chirality. This indicates that the introduction of the point chirality in the ligands enables the efficient stereoselective construction of mechanically interlocked molecules. Furthermore, by using ligands containing d-alanine residues, radial [5]catenanes with the opposite planar chirality and opposite co-conformational mechanical helical chirality have also been obtained.


Properties and mechanism of action of pyruvate, phosphate dikinase from leaves.
1. Sugar-cane leaf pyruvate,P(i) dikinase was prepared free of enzymes that would interfere with studies on the stoicheiometry and mechanism of the reaction it catalyses. The reaction was unequivocally shown to involve the conversion of equimolar amounts of pyruvate, ATP and P(i) into phosphoenolpyruvate, AMP and PP(i). 2. The purified enzyme was stable at pH8.3 only if stored at about 20 degrees in the presence of Mg(2+) and a thiol-reducing reagent, care being taken to prevent the oxidation of the thiol. 3. The apparent Michaelis constants for phosphoenolpyruvate and PP(i) were 0.11mm and 0.04mm respectively and that for AMP was less than 4mum. 4. At pH8.3 the initial velocity of the reaction was about 6 times as fast in the direction towards phosphoenolpyruvate synthesis as in the reverse direction. 5. With the exception of ATP, all the products of the reaction in both directions were inhibitory. 6. The phosphate groups of PP(i) were derived from P(i) and from the terminal phosphate of ATP. 7. Isotope-exchange studies indicated that the reaction proceeds in the following steps:Enzyme+ATP+P(i) right harpoon over left harpoon Enzyme-P+AMP+PP(i)Enzyme-P+pyruvate right harpoon over left harpoon Enzyme+phosphoenolpyruvate


Determination of trans-10-hydroxy-2-decenoic acid content in pure royal jelly and royal jelly products by column liquid chromatography.
In this research, several royal jellies and commercial products containing royal jelly were analysed for their trans-10-hydroxy-2-decenoic acid (10-HDA) content by using a column liquid chromatography technique. Ten samples claimed to be pure royal jelly, containing 10-HDA between 0.75 and 2.54%. Seven samples claimed to contain royal jelly as an ingredient which ranged from non-detectable to 0.054%. The technique was found to be rapid with high recovery.


One-pot synthesis of pyrrolo[1,2-a]quinoxalines.
A transition metal-free process for the regioselective synthesis of pyrrolo[1,2-a]quinoxalines under mild conditions in one-pot is described. The reaction afforded a variety of products in good to excellent yields. Indolo[1,2-a]quinoxalines were also synthesized from indole-2-carboxamides under the same conditions.


Effects of acute and subchronic administration of dexefaroxan, an alpha(2)-adrenoceptor antagonist, on memory performance in young adult and aged rodents.
The present study examined the influence of dexefaroxan, a potent and selective alpha(2)-adrenoceptor antagonist, on cognitive performance in rodents. In young adult rats, dexefaroxan reversed the deficits induced by UK 14304 [5-bromo-N-(4,5-dihydro-1-H-imidazol-2-yl)-6-quinoxalinamine], scopolamine, and diazepam in a passive avoidance task. In this test, dexefaroxan also attenuated the spontaneous forgetting induced by a 15-week training-testing interval. Moreover, dexefaroxan, given immediately after training, increased the memory performance of rats trained with a weak electric footshock in the passive avoidance test, facilitated spatial memory processes in the Morris water maze task in rats, and increased the performance of mice in an object recognition test. Thus, dexefaroxan appears to have a promnesic effect in these tests by facilitating the processes of memory retention, rather than acquisition or other noncognitive influences. The facilitatory effects of dexefaroxan in young adult rats persisted even after a 21- to 25-day constant subcutaneous infusion by using osmotic minipumps, indicating that tolerance to the promnesic effect of the drug did not occur during this prolonged treatment interval. Furthermore, in the passive avoidance and Morris water maze tests, dexefaroxan ameliorated the age-related memory deficits of 24-month-old rats to a level that was comparable to that of young adult animals, and reversed the memory deficits induced by excitotoxin lesions of the nucleus basalis magnocellularis region. Together, these findings support a potential utility of dexefaroxan in the treatment of cognitive deficits occurring in Alzheimer's disease.


Vibrational spectroscopic studies of L,D-alternating phenylalanine peptides.
Infrared and Raman spectra of Boc-(D-Phe-L-Phe)n-OMe, with n = 4 and 5, and Boc-L-Phe-(D-Phe-L-Phe)7-OMe, have been obtained in crystalline and solution states. Based on the earlier spectroscopic studies on Boc-(L-Val-D-Val)n-OMe, with n = 4, 6 and 8, and the predictions from the normal-mode calculations of double-stranded beta-helix conformations, structures have been assigned for the three oligopeptides. In the crystalline state, all three oligopeptides have a double-stranded increases decreases beta 5.6 structure. Spectra from chloroform solution indicate that the solid-state conformation is retained in this solvent for all three oligopeptides.


Apparatus for studying fretting fatique in vacuum.
Recent investigations on the mechanism of fretting fatigue have indicated that mechanical damage, not chemical corrosion, has the largest effect in decreasing structural component life. Since there is no general agreement on the mechanism of fretting fatigue, an experiment has been designed to evaluate statistically the relative role of the mechanical process and the chemical process in reducing fatigue life. An initial step was to develop an apparatus that allows fretting fatigue tests to be performed in both laboratory air and vacuum environments. A detailed discussion of the experimental apparatus and experimental procedure are presented in this paper. Also typical test results are presented. It is found that fretting fatigue in vacuum is about ten times slower than that in laboratory air. Fractographic analysis of the wear surface indicated that less severe fretting damage occurred in the vacuum environment.


[Prior infected influenza virus could protect mice from challenge of lethal influenza virus].
To determine whether it could protect mice from challenge of lethal influenza virus which group prior infected A(H1N1) pdm09 and H9N2 virus respectively. 150 BALB/c mice are divided into three groups. Mice are infected A(H1N1) pdm09 virus (pCA07) and poultry H9N2 virus (GZ333) respectively. Infected mice are challenged with 10 times of lethal dose virus (PR8) then compare the viral load, antibody and survival of the two group mice before and after challenged. Both experimental group mice survived after challenge of lethal influenza virus and lung viral load are lower than that of the first infection. Antibodies derived from the infective virus and challenge virus. Prior infected A(H1N1) pdm09 and H9N2 virus could protect mice from challenge of lethal influenza virus.


Supporting gender-diverse young people: the role of the nurse.
Gender-diverse individuals will need to access healthcare services for various reasons, with most of this care provided outside of specialist gender services. Nurses have an important role in advocating for the specific needs of gender-diverse individuals and providing person-centred care. Therefore, they have a responsibility to ensure their knowledge of appropriate terminology and gender-affirming interventions is up to date. This article provides information about gender diversity to enhance nurses' understanding of this area to enable them to care for gender-diverse people effectively and sensitively. While the focus of this article is on gender-diverse young people, the same principles can be applied across all age groups.


Retrospective analysis of spinal arachnoid cysts in 14 dogs.
Spinal cord dysfunction secondary to spinal arachnoid cysts (SACs) has been reported previously in dogs. This retrospective study reviews the clinical signs, radiographic findings, and outcome after surgical resection of SACs in 14 dogs. Plain vertebral column radiographs and myelography were done in all dogs. Computed tomography (CT) was done in 7 dogs and magnetic resonance (MR) imaging in 3 dogs. Affected dogs were between 1 and 12 years of age, and 8 of 14 were Rottweilers. Abnormalities detected on neurological examination depended on the location of the SAC. Five dogs had bilobed or multiple SACs. SACs were located in the cervical vertebral column in 11 dogs and in the thoracic vertebral column in 4 dogs. All dogs had dorsally or dorsolaterally located SACs. Two dogs also had additional ventrally located SACs. Spinal cord compression secondary to intervertebral disc extrusion or protrusion was demonstrated at the site of the SACs in 2 dogs. Surgical resection of the SACs was completed in all dogs. Eleven dogs were available for follow-up. Five weeks postoperatively, 7 dogs improved in neurological function, with some residual ataxia and paresis in 6 of these dogs. Neurological function had deteriorated in 4 dogs. It was concluded from this study that Rottweilers have a higher incidence of SACs than other breeds of dog. Furthermore, bilobed or multiple SACs can occur commonly, and myelography effectively localized SACs in dogs. Surgical resection of SACs resulted in improvement in neurological function in the majority of treated dogs.


Instrumental Music Educators in a COVID Landscape: A Reassertion of Relationality and Connection in Teaching Practice.
For many countries instrumental music tuition in secondary schools is a ubiquitous event that provides situated and personalized instruction in the learning of an instrument. Opportunities and methods through which teachers operate during the COVID-19 outbreak challenged music educators as to how they taught, engaged, and interacted with students across online platforms, with alarm over aerosol dispersement a major factor in maintaining online instrumental music tuition even as students returned to "normal" face to face classes. This qualitative study investigated the practices employed by instrumental music educators in secondary schools in Melbourne, Australia, analyzing teacher perspectives to music tuition amidst the restriction of interaction with students remotely via online means. Thematic analysis of the interview transcripts revealed music educational approaches that fostered connection, empathy and receptiveness to relationship-building, guiding students in slower and deeper learner-centered approaches, asserting pedagogical practices that reinforced and promoted interpersonal connectedness in and through musical experience and discovery. These findings provide a framework for how music educators can facilitate connection, motivation and student autonomy generating personal meaning and commitment to music making and the learning relationship, which can translate to significant student learning and value in the learning music. Exploring teachers' pedagogical practices and behaviors within this dyadic teacher-student relationship is a significant addition to the literature, enabling the consideration of the type of connective behaviors required to stimulate and develop long-term interest in music.


Repression of a large number of genes requires interplay between homologous recombination and HIRA.
During homologous recombination, Dbl2 protein is required for localisation of Fbh1, an F-box helicase that efficiently dismantles Rad51-DNA filaments. RNA-seq analysis of dbl2Δ transcriptome showed that the dbl2 deletion results in upregulation of more than 500 loci in Schizosaccharomyces pombe. Compared with the loci with no change in expression, the misregulated loci in dbl2Δ are closer to long terminal and long tandem repeats. Furthermore, the misregulated loci overlap with antisense transcripts, retrotransposons, meiotic genes and genes located in subtelomeric regions. A comparison of the expression profiles revealed that Dbl2 represses the same type of genes as the HIRA histone chaperone complex. Although dbl2 deletion does not alleviate centromeric or telomeric silencing, it suppresses the silencing defect at the outer centromere caused by deletion of hip1 and slm9 genes encoding subunits of the HIRA complex. Moreover, our analyses revealed that cells lacking dbl2 show a slight increase of nucleosomes at transcription start sites and increased levels of methylated histone H3 (H3K9me2) at centromeres, subtelomeres, rDNA regions and long terminal repeats. Finally, we show that other proteins involved in homologous recombination, such as Fbh1, Rad51, Mus81 and Rad54, participate in the same gene repression pathway.


Improvement of electrophoretic enantioseparation of amlodipine by polybrene.
In chiral and non-chiral electrophoretic resolution of basic drugs, adsorption of analytes to negatively charged capillary wall could lead to poor repeatability of migration time and peak area. In addition, chiral resolutions of basic drugs are commonly performed in low pH buffers. Therefore, longer analysis time due to suppression of electroosmotic flow (EOF) is another dilemma. In this work the improvement effect of polybrene (PB), a cationic polymer, on chiral separation of a model basic drug, amlodipine (AML), was investigated. PB both as a semi-permanent coating agent and as an additive in the running buffer was utilized. Better results were obtained with PB as a buffer additive. Compare to untreated bare silica without using PB in running buffer, addition of 0.0005% PB buffer decreased analysis time downed to 3 folds; efficiency improved up to 5 folds; limit of detection (LOD) and limit of quantification (LOQ) downed to 8 folds and within-day migration time and peak area repeatabilities, in terms of relative standard deviations (RSD) downed to 5 and 20 folds, respectively.


Differential contribution to neuroendocrine tumorigenesis of parallel egfr signaling in cancer cells and pericytes.
Factors associated with tumor sensitivity to epidermal growth factor receptor (EGFR) inhibitors in the context of wild-type EGFR remain elusive. This study investigates the mechanistic basis of responsiveness to EGFR inhibitors in the RIP1-Tag2 (RT2) mouse model of pancreatic neuroendocrine tumorigenesis (PNET). Upon treatment of RT2 mice with EGFR inhibitors, PNET tumors harboring wild-type, nonamplified alleles of Egfr grow at a markedly reduced rate and display a significant increase in tumor cell apoptosis, as well as reduced neovascularization. The authors identify Tgf-α and Hb-egf as key limiting mediators of separable pathological functions of Egfr in neuroendocrine tumor progression: Tgf-α mutant tumors present with an elevated apoptotic index, whereas Hb-egf mutant lesions exhibit decreased angiogenic switching and neovascularization. This study not only associates Tgf-α and Hb-egf expression with wild-type Egfr oncogenicity but also ascribes the proangiogenic activity of Egfr in this tumor model to a novel mesenchymal Hb-egf/Egfr signaling axis, whereby endothelial and pericyte-derived Hb-egf activates Egfr specifically in tumor-associated perivascular cells, leading to increased pericyte coverage of the tumor endothelium and enhanced angiogenesis.


Chemometric Optimization of Biologically Active Compounds Extraction from Grape Marc: Composition and Antimicrobial Activity.
The article focuses on the optimization of the extraction process of biologically active compounds (BAC) from grape marc-a by-product of the wine industry. The influence of temperature, specifically 30 °C, 45 °C and 65 °C, and ethanol concentration in solutions, specifically 0-96% (v/v) on the extraction yield of polyphenols, flavonoids, tannins and anthocyanins, were investigated. The composition of individual polyphenols, anthocyanins and organic acids, antioxidant activity (DPPH and ABTS) and CIELab chromatic characteristics of the grape marc extracts (GME), were characterized. The microbiostatic and microbicidal effects in direct contact of GME with pathogenic microorganisms, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, were determined in vitro. The influence of extraction parameters on the total polyphenol content (TPC), total flavonoid content (TFC), tannin content (TC), total anthocyanin content (TAC) and their interdependencies were studied using information analysis. A mathematical model was developed on cubic spline functions. The analysis of individual compounds showed the presence of a wide range of flavonoids (procyanidin B2, procyanidin B1, hyperoside and quercetin), flavones (catechin), hydroxybenzoic acid derivatives (gallic, protocatechuic, p-hydroxybenzoic acids, m-hydroxybenzoic acid, syringic acid), hydroxycinic acid derivatives and ferulic acid methyl ester. The malvidol-3-glucoside was the main anthocyanin identified in the extract. A high amount of tartaric acid was also found. GME showed significant antimicrobial activity against Gram-positive bacteria and lower activity against Gram-negative bacteria.


Isomer specificity of conjugated linoleic acid (CLA): 9E,11E-CLA.
Conjugated linoleic acids (CLA) were identified in 1980's, since then it has been intensively studied due to its various beneficial health effects such as anti-inflammatory, anti-atherogenic, anti-carcinogenic and anti-diabetic/obesity effects. Isomer specificity of a number of CLA isomers, especially predominant isomer 9Z,11E- and 10E,12Z-CLA, is now recognized. However, the less prevalent CLA isomers have not been well characterized. Recently, studies have reported the distinctively different effects of 9E,11E-CLA in colon cancer cells, endothelial cells, and macrophage cells compared to the rest of CLA isomers. In this review, various effects of CLAs, especially anti-inflammatory and anti-atherogenic effects, will be discussed with focusing on the isomer-specific effects and potential mechanism of action of CLA. At last, recent studies about 9E,11E-CLA in in vitro and animal models will be discussed.


Lessons from more than 80 structures of the GluA2 ligand-binding domain in complex with agonists, antagonists and allosteric modulators.
Ionotropic glutamate receptors (iGluRs) constitute a family of ligand-gated ion channels that are essential for mediating fast synaptic transmission in the central nervous system. These receptors play an important role for the development and function of the nervous system, and are essential in learning and memory. However, iGluRs are also implicated in or have causal roles for several brain disorders, e.g. epilepsy, Alzheimer's disease, Parkinson's disease and schizophrenia. Their involvement in neurological diseases has stimulated widespread interest in their structure and function. Since the first publication in 1998 of the structure of a recombinant soluble protein comprising the ligand-binding domain of GluA2 extensive studies have afforded numerous crystal structures of wildtype and mutant proteins including different ligands. The structural information obtained combined with functional data have led to models for receptor activation and desensitization by agonists, inhibition by antagonists and block of desensitization by positive allosteric modulators. Furthermore, the structural and functional studies have formed a powerful platform for the design of new selective compounds.


Ultra-fast dye sensitisation and co-sensitisation for dye sensitized solar cells.
We present a rapid (5 min) and controlled sensitisation method for dye sensitized solar cells which gives 6.0% for the Ru dye N719 and 3.7% for the IR absorbing squaraine SQ1. Rapid co-sensitization (N719 and SQ1) gives efficiencies up to 7.9%. Devices have similar or better efficiency to those dyed passively for 18 h.


A structural foundation for studying chlamydial polymorphic membrane proteins.
Infections by bacteria in the genus Chlamydia cause a range of widespread and potentially debilitating conditions in humans and other animals. We analyzed predicted structures of a family of proteins that are potential vaccine targets found in all Chlamydia spp. Our findings deepen the understanding of protein structure, provide a descriptive framework for discussion of the protein structure, and outline regions of the proteins that may be key targets in host-microbe interactions and anti-chlamydial immunity.


Predictability and Vector Analysis of Laser In Situ Keratomileusis for Residual Errors in Eyes Implanted With Different Multifocal Intraocular Lenses.
To investigate potential differences in predictability, efficacy, and safety of corneal excimer laser to correct residual myopia, hyperopia, and astigmatism in eyes previously implanted with multifocal intraocular lenses using distinct optical surfaces and platforms for multifocality. This prospective comparative study included 37 eyes submitted to laser in situ keratomileusis correction for residual errors after implantation of either an apodized diffractive-refractive (Restor) or a full-diffractive (Tecnis) multifocal intraocular lens. Data analysis included investigation of predictability, efficacy, and safety of excimer laser surgery to correct residual errors. A double-angle plot, using vector analysis, was also created to evaluate predictability of astigmatism correction. At 6-month follow-up, statistical analyses revealed a significant improvement when comparing preoperative (0.51 ± 0.25 and 0.44 ± 0.18) and postoperative values (0.17 ± 0.10 and 0.09 ± 0.07) of uncorrected distance visual acuity (P < 0.0001 and <0.0001), preoperative (0.92 ± 0.61 and 1.02 ± 0.45) and postoperative values (0.33 ± 0.23 and 0.19 ± 0.17) of manifest refractive spherical equivalent (P = 0.0006 and <0.0001), and preoperative (-1.08 ± 0.70 and -0.65 ± 0.42) and postoperative values (-0.25 ± 0.28 and -0.14 ± 0.21) of astigmatism (P < 0.0001 and <0.0001) in eyes implanted with Restor and Tecnis, respectively. Vector analysis revealed a predictable correction of astigmatism in all groups. Ninety-two percent of total eyes achieved a manifest refractive spherical equivalent within ±0.5 of emmetropia. Corneal excimer laser refractive surgery seems to be equally effective to correct different residual errors, including astigmatism, in eyes implanted with intraocular lenses with various platforms for multifocality.


Ultrastructural study of the initial phases of pancreatic carcinoma induced by BOP in the Syrian golden hamster.
A serial study was carried out on the lesions induced by N-nitroso-bis(2-oxopropyl)amine (BOP) in the Syrian golden hamster until the appearance of pancreatic ductal carcinomas. During the initial phase, first findings were cytolysis of acinar cells close to blood vessels and other cells, together with a loss of zymogen granules from the cytoplasm, and an increase in the diameters of the acinar lumens. After week 11 a proliferation of ductule-like cells was observed. We consider that a minimum proliferation of cells at the acinus-ductule junction would give rise to pseudoductules composed of remains of acinar cells together with ductule-like cells.


Fractionation and Analysis of Polypeptides of Euglena gracilis Chloroplasts.
Intact Euglena gracilis chloroplasts, purified on gradients of silica sol, were lysed osmotically and fractionated by centrifugation on discontinuous gradients of sucrose into their soluble, envelope membrane, and thylakoid membrane components. The proteins of the different subchloroplast fractions, as well as those of whole chloroplasts, were analyzed by electrophoresis on sodium dodecyl sulfate polyacrylamide gels. The polypeptide profile of each fraction was distinctive and was in general similar to the profile obtained for analogous fractions of the chloroplasts of higher plants.The envelope membranes were separated into two fractions in the gradients according to their banding densities. Electron micrographs showed that the light envelope fraction consisted mostly of single-membrane vesicles, whereas the heavy envelope fraction consisted of multiple layers of folded membranes. Both envelope fractions were ultrastructurally distinct from the thylakoid membranes.


Extensive defects of mitochondrial electron-transfer chain in muscular cytochrome c oxidase deficiency.
This study was undertaken to estimate the extent of molecular defects in the mitochondrial electron-transfer chain of a patient with mitochondrial myopathy. Biochemical and immunochemical studies were performed on the skeletal muscle mitochondria. Spectrophotometry and enzyme activity measurements localized a definite defect at the segment of cytochrome c oxidase (complex IV) of the electron-transfer chain. Immunoblotting and immunoprecipitation studies using the anti-complex IV antibody revealed that the contents of subunits 1, 4, 5, 6, and 7 of complex IV were markedly diminished and that subunit 2 was almost absent. Immunohistochemistry of the muscle tissue revealed a considerable accumulation of immunoreactive materials of complex IV in the ragged-red fibers. The immunoblots using the anti-NADH-ubiquinone oxidoreductase antibody demonstrated that the contents of NADH-ubiquinone oxidoreductase subunits were 47% of control and that the contents of three subunits were considerably decreased. The contents of ubiquinol-cytochrome c oxidoreductase subunits were also somewhat low (77% of control) and one of the minor contaminants detected in the control was completely absent. High-resolution one-dimensional sodium dodecyl sulfate-urea-gel electrophoresis disclosed that six additional unidentified polypeptides in the control were markedly diminished or completely missing. These results demonstrate that the molecular defects in the mitochondrial electron-transfer chain are more extensive than would be expected from either spectral analysis or enzyme activity measurements alone, and involve not only complex IV but also NADH-ubiquinone oxidoreductase and ubiquinol-cytochrome c oxidoreductase and several unidentified mitochondrial proteins.


Lung morphology-perfusion correlation on perfusion SPECT-CT fusion images in two cases of septic pulmonary embolism.
Septic pulmonary embolism (SPE) is a critical disorder which requires fast diagnosis for treatment, while SPE continues to pose a diagnostic challenge in radiologic imaging. We describe detailed findings on breath-hold perfusion SPECT-CT fusion images in 2 patients with SPE. Regardless of absence or nonspecific morphologic abnormality in these patients, the fusion images showed multiple wedge-shaped segmental/subsegmental perfusion defects along specific pulmonary arteries, highly suggesting embolic event. Follow-up fusion images after treatment showed changes in lung perfusion defects and morphology. Assessment of lung morphology-perfusion correlation on reliable fusion images contributes to correct diagnosis of SPE and monitoring of treatment effect.


Efficient Hydrogen Generation and Total Nitrogen Removal for Urine Treatment in a Neutral Solution Based on a Self-Driving Nano Photoelectrocatalytic System.
Urine is the main source of nitrogen pollution, while urea is a hydrogen-enriched carrier that has been ignored. Decomposition of urea to H2 and N2 is of great significance. Unfortunately, direct urea oxidation suffers from sluggish kinetics, and needs strong alkaline condition. Herein, we developed a self-driving nano photoelectrocatalytic (PEC) system to efficiently produce hydrogen and remove total nitrogen (TN) for urine treatment under neutral pH conditions. TiO2/WO3 nanosheets were used as photoanode to generate chlorine radicals (Cl•) to convert urea-nitrogen to N2, which can promote hydrogen generation, due to the kinetic advantage of Cl-/Cl• cyclic catalysis. Copper nanowire electrodes (Cu NWs/CF) were employed as the cathode to produce hydrogen and simultaneously eliminate the over-oxidized nitrate-nitrogen. The self-driving was achieved based on a self-bias photoanode, consisting of confronted TiO2/WO3 nanosheets and a rear Si photovoltaic cell (Si PVC). The experiment results showed that hydrogen generation with Cl• is 2.03 times higher than in urine treatment without Cl•, generating hydrogen at 66.71 μmol h-1. At the same time, this system achieved a decomposition rate of 98.33% for urea in 2 h, with a reaction rate constant of 0.0359 min-1. The removal rate of total nitrogen and total organic carbon (TOC) reached 75.3% and 48.4% in 2 h, respectively. This study proposes an efficient and potential urine treatment and energy recovery method in neutral solution.