Salvage of Implant-Based Breast Reconstruction in Nipple-Sparing Mastectomies With Autologous Flaps.
Implant-based breast reconstruction (IBR) after nipple-sparing mastectomies (NSM) can have complications that require explantation of a tissue expander or permanent prosthesis. When complications occur, preservation of the nipple-areola complex (NAC) remains critical to ensure aesthetic breast reconstruction. To date, there are minimal data on outcomes for patients experiencing unplanned explantations in IBR after NSM. To evaluate final reconstructive outcomes for NSM patients who undergo IBR and have an unplanned explanation and to separately analyze the outcome of the NAC aesthetic subunit. We analyzed a prospectively maintained database of NSM patients undergoing IBR reconstruction at a single institution to identify patients who had complications resulting in unplanned explanation. Demographics, covariates, and reconstructive outcomes, including salvage with IBR or autologous flaps, were assessed. Final outcomes of the NAC were also evaluated. A total of 213 patients underwent 382 NSM with IBR with either direct-to-implant (DTI) or tissue expander/implant (TE/I) reconstructions. The complication rate was 15.2% (N = 58) and 33 (8.6%) unplanned explantations occurred: 23 (69.8%) of whom ultimately completed reconstruction with either IBR (30.4%) or autologous flaps (69.6%). NACs were preserved in 62.5% of breasts with unplanned explantations. Only 8 NACs were lost in the entire cohort (2.1%). Following unplanned explantations in IBR after NSM, salvage can be performed with either IBR or autologous flaps. However, the majority of salvage procedures in IBR after NSM will be with autologous flaps that bring in healthy soft tissue to restore location specific defects caused by complications. The NAC can ultimately be preserved as an aesthetic subunit in most patients despite the occurrence of initial complications.


Lycopene enhances bone neoformation in calvaria bone defects of ovariectomized rats.
Osteoporosis can affect a significant part of the population and fractures are the most common complications associated with this disease, leading to high public health costs. Thus, the prevention of fractures is relevant to individuals with signs and symptoms as well as to the health system. Postmenopausal osteoporosis has been associated with oxidative stress, emphasizing the importance of an efficient defense system to maintain bone health. Lycopene is a carotenoid with antioxidant properties that may stimulate osteoblastogenesis and inhibit osteoclastogenesis. The purpose of this investigation was to analyze the influence of lycopene in the bone neoformation of calvaria defects in ovariectomized rats utilizing the concentration of 45 mg/kg. Wistar Hannover female rats were divided into ovariectomized and sham groups. The ovariectomized animals received 45 mg/kg lycopene (OvxL) or water (Ovx) by daily gavage the day after ovariectomy/sham surgery for 16 weeks. Twelve weeks after ovariectomy, there were performed 5-mm calvaria defects followed by euthanasia after 4 weeks. Samples of bone tissue were collected to perform morphological and morphometrical analysis of the neoformed bone area, and percentage with Software Image J. Morphological evaluation showed mature bone with more osteocytes in the group OVxL when compared to the other groups. The morphometrical analysis demonstrated a significant increase of bone neoformation in the group OvxL (p<0.05). The data obtained suggest that lycopene benefits bone repair in the absence of estrogenic hormones.


Creating an Optimal IP Learning Environment: NCICLE Pathways to Excellence.
Clinical learning environments are a shared space for various professions working together to provide the best care for patients. The National Collaborative for Improving the Clinical Learning Environment (NCICLE) published the NCICLE Pathways to Excellence: Expectations for an Optimal Interprofessional Clinical Learning Environment to Achieve Safe and High-Quality Patient Care as a tool that can be used to assess and develop ways to optimize learning and patient care. This framework provides guidance for health care professionals to collaborate with executives to transform the clinical learning environment and patient outcomes. [J Contin Educ Nurs. 2022;53(4):150-152.].


High protein and mRNA expression levels of TUBB3 (class III ß-tubulin) are associated with aggressive tumor features in esophageal adenocarcinomas.
Esophageal adenocarcinomas show an increasing incidence in the Western world and their overall survival remains low. Microtubules are multifunctional cytoskeletal proteins involved in crucial cellular roles, including maintenance of cell shape, intracellular transport, meiosis, and mitosis. Microtubulus-TUBB3 was found overexpressed in several carcinomas suggesting a significant role in cancer development. High levels of TUBB3 expression were also described to be associated with poor clinical outcome in various cancers. It was shown that overexpression of TUBB3 could be related to reduced efficiency of taxane-based targeting anticancer drugs in several cancer types. There is a statistically significant association between high TUBB3 protein and TUBB3 mRNA expression and shortened survival (p<0,0001). Prognostic impact of TUBB3 expression is seen in patients with and without multimodal treatment. Multivariate analysis revealed a strong TUBB3 expression to be an independent prognosis factor. Validation of protein expression by mRNA in situ hybridization underlines the credibility of the immunohistochemical results. Our study emphasized the significant importance of TUBB3 in esophageal adenocarcinoma. TUBB3 serves as an independent prognostic marker and may be a valuable biomarker for routine application in esophageal adenocarcinoma especially to address the need for adjuvant treatment in individuals following neoadjuvant therapy and surgery. Future prospective studies are needed which include the results of TUBB3 in preoperative biopsy material to proof the prognostic impact of TUBB3. 280 esophageal adenocarcinomas that underwent primary surgical resection or resection after neoadjuvant therapy were analyzed by mRNA-in-situ-hybridization (RNAscope®) and by immunohistochemistry (TUBB3 rabbit monoclonal antibody; Epitomics).


Restoration of X-ray resistance and V(D)J recombination in mutant cells by Ku cDNA.
Three genetic complementation groups of rodent cells are defective for both repair of x-ray-induced double-strand breaks and V(D)J recombination. Cells from one group lack a DNA end-binding activity that is biochemically and antigenically similar to the Ku autoantigen. Transfection of complementary DNA (cDNA) that encoded the 86-kilodalton subunit of Ku rescued these mutant cells for DNA end-binding activity, x-ray resistance, and V(D)J recombination activity. These results establish a role for Ku in DNA repair and recombination. Furthermore, as a component of a DNA-dependent protein kinase, Ku may initiate a signaling pathway induced by DNA damage.


Urgent-Start Peritoneal Dialysis as a Bridge to Definitive Chronic Renal Replacement Therapy: Short- and Long-Term Outcomes.
Background: The peritoneal dialysis (PD) urgent-start pathway, without typical 2-week break-in period, was meant for late-referral patients able and prone to join PD-first program, with its main advantages such as: keeping the vascular system intact, preserving their residual renal function and retaining life-style flexibility. We compared the short- and long-term outcomes of consecutive 35 patients after urgent- and 94 patients after the planned start of PD as the first choice. Methods: The study included all incident end-stage renal disease patients starting PD program between January 2005 and December 2015, classified into two groups: those with urgent (unplanned) and those with elective (planned) start. Urgent PD was initiated as an overnight automatic procedure (APD) with dwell volume gradually increased, and after 2-3 weeks, target PD method was established. Results: The mean time between catheter implantation and PD start was 3.5 ± 2.3 in urgent and 16.2 ± 1.7 days in planned-start groups (p < 0.00001). 51% of the patients in the urgent-start group required PD during first 48 h after catheter insertion. Mean follow-up of 17.6 ± 11.09 months (median: 19.0) was in the urgent-start group and 28.6 ± 26.6 months (median: 19.5) in the planned-start group. The early mechanical complications were observed more often in the urgent-start group (29 vs. 4%, p = 0.00005). The only significant predictors of early mechanical complications were serum albumin (p = 0.02) and time between the catheter insertion and PD start. The first year patient survival and technique survival censored for death and kidney transplantation were not significantly different between groups. In Cox proportional analysis the independent risk factors for patient survival as well as for method and patient survival appeared Charlson Comorbidity Index CCI (HR 1.4; p = 0.01 and 1.24; p = 0.02) and time from catheter implantation to PD start with HR 5.11; p = 0.03 and 4.29; p = 0.04 for <2 days, while time >14 days lost its predictive value (p = 0.07). Conclusion: Peritoneal dialysis may be a feasible and safe alternative to HD in patients who need to start dialysis urgently without established dialysis access, with an acceptable complications rates, as well as patient and technique survival.


Cancer-associated fibroblasts and their role in tumor progression.
The stromal elements of a malignant tumor can promote cancer progression and metastasis. The structure of the tumor stroma includes connective tissue elements, blood vessels, nerves, and extracellular matrix (ECM). Some of the cellular elements of the tumor stroma are cancer-associated f ibroblasts (CAFs). The origin and function of CAFs have been actively studied over the past thirty years. CAFs produce collagen, the main scaffold protein of the extracellular matrix. Collagen in the tumor stroma stimulates f ibrosis, enhances the rigidity of tumor tissue, and disrupts the transmission of proliferation and differentiation signaling pathways. CAFs control tumor angiogenesis, cell motility, tumor immunogenic properties, and the development of resistance to chemo- and immunotherapy. As a result of metabolic adaptation of rapidly growing tumor tissue to the nutrients and oxygen deprivation, the main type of energy production in cells changes from oxidative phosphorylation to anaerobic glycolysis. These changes lead to sequential molecular alterations, including the induction of specif ied transcriptional factors that result in the CAFs activation. The molecular phenotype of activated CAFs is similar to f ibroblasts activated during inf lammation. In activated CAFs, alpha-smooth muscle actin (α-SMA) is synthetized de novo and various proteases and f ibronectin are produced. Since CAFs are found in all types of carcinomas, these cells are potential targets for the development of new approaches for anticancer therapy. Some CAFs originate from resident f ibroblasts of the organs invaded by the tumor, while others originate from epithelial tumor cells, which are undergoing an epithelial-mesenchymal transition (EMT). To date, many molecular and metabolic inducers of the EMT have been discovered including the transforming growth factor-beta (TGF-β), hypoxia, and inf lammation. This review classif ies modern concepts of molecular markers of CAFs, their functional features, and discusses the stages of epithelial- mesenchymal transition, and the potential of CAFs as a target for antitumor therapy.


Role of polyamines and their antimetabolites in clinical medicine.
Polyamine research, which began with a clinical observation more than 300 years ago, has progressed for several decades as pure basic research, sometimes considered as an academic triviality. The role of polyamines in clinical medicine is coming of age. The fruits of polyamine research are just now entering into the realm of practical application and in a very multidisciplinary manner. Basic research on polyamine metabolism and the elucidation of their physiologic functions has involved many academically interesting, even revolutionary, aspects, but the imagination of biochemists and cell biologists may no longer be sufficient to discover the best ways to translate the results of this basic research into clinical practice. It is almost certain that polyamine antimetabolites will soon find their place among the drug regimens used for the treatment of human malignancies and, possibly, also of hyperproliferative skin diseases. The elucidation of the role of polyamines in cell differentiation may offer fundamental applications regarding the regulation of cell cycle events. The discovery of the antiparasitic properties of polyamine antimetabolites may have a major impact on the well-being of millions of people in the developing world. The potential application of polyamine research in microbial and viral diseases is an area in which investigational insight is just beginning. Finally, the clinical chemistry of extracellular polyamines, although initially disappointing, has not yet been explored in depth and may offer applications useful for the diagnosis or follow-up of a variety of common diseases.


Chemical modification of tryptophanase by chloramine T: a possible involvement of the methionine residue in enzyme activity.
Tryptophanase purified from Escherichia coli B/1t7-A was irreversibly inactivated by chloramine T (sodium N-chloro-p-toluenesulfonamide). The mode of inactivation was rather complex and did not follow pseudo-first-order kinetics. The inactivation of the apoenzyme was much faster than that of the holoenzyme. The Km value for the synthetic substrate S-o-nitrophenyl-L-cysteine (SOPC) increased concomitantly with the modification. In contrast, the Km value for the coenzyme, pyridoxal 5'-phosphate (PLP), was not altered. L-Serine, another substrate, and L-alanine, a competitive inhibitor, protected the enzyme from inactivation. Determination of SH groups in the enzyme protein with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) showed that modification of two SH groups per enzyme subunit resulted in a complete inactivation. When the enzyme was subjected to chloramine T-modification following the SH group modification with DTNB, further inactivation was still observed, even after the addition of dithiothreitol. The SH-blocked enzyme preparation thus obtained, however, exhibited less pH dependency of inactivation by chloramine T than that of the native enzyme. The amino acid analysis of the chloramine T-modified enzyme showed that modification of four or five methionine residues among the 16 residues per subunit proceeded concomitantly with the complete inactivation. Modification of the enzyme with chloramine T quenched the absorption peak near 500 nm, characteristic of a quinoidal structure formed by labilization of the alpha-proton. These results suggest the possibility that chloramine T modifies not only the SH groups, but also methionine residues important for the catalytic activity of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)


Small-bowel obstruction: a review of 465 cases.
A retrospective review of experience with small-bowel obstruction at the University Hospital in Birmingham for a ten-year period (January 1963 through December 1972) revealed 465 episodes of obstruction in 415 patients. The mortality was 4% in obstruction due to adhesions, and 28% in obstruction caused by carcinoma; overall mortality was 8%. Intra-abdominal adhesions were the cause of 69% of cases. Malignant obstruction (mostly from metastatic disease) was the second most common cause of obstruction, and external hernia was third. Delay in diagnosis and inappropriately prolonged used of long intestinal tubes added to the mortality and can be avoided. We suggest a plan for prompt, consistent diagnosis and recommend more liberal use of the barium meal in questionable cases.


Are Narrow Focus Exhaustivity Inferences Bayesian Inferences?
In successful communication, the literal meaning of linguistic utterances is often enriched by pragmatic inferences. Part of the pragmatic reasoning underlying such inferences has been successfully modeled as Bayesian goal recognition in the Rational Speech Act (RSA) framework. In this paper, we try to model the interpretation of question-answer sequences with narrow focus in the answer in the RSA framework, thereby exploring the effects of domain size and prior probabilities on interpretation. Should narrow focus exhaustivity inferences be actually based on Bayesian inference involving prior probabilities of states, RSA models should predict a dependency of exhaustivity on these factors. We present experimental data that suggest that interlocutors do not act according to the predictions of the RSA model and that exhaustivity is in fact approximately constant across different domain sizes and priors. The results constitute a conceptual challenge for Bayesian accounts of the underlying pragmatic inferences.


[The history of training at the Société psychoanalytique de Paris].
As from its creation in 1926, the Société psychanalytique de Paris took charge of organizing the transmission of psychoanalysis by founding a first Institut whose activities came to an end in 1940. As from the founding of a second Institut de Psychanalyse by S. Nacht in 1954, the training of psychoanalysts was to follow an orientation that was particular to the Société psychanalytique de Paris. Specific conflicts pertaining to the question of psychoanalytic training, the scisson of the Société psychanalytique de Paris and the evolution of the psychoanalytic movement in France were determining factors in the evolution of training at the Institut. The selection of candidates, didactic analysis, supervision, teaching and details concerning the training program are presented in their evolution.


The Role of Electrostatic Interactions in Binding of Histone H3K4me2/3 to the Sgf29 Tandem Tudor Domain.
Several reader domain proteins that specifically recognize methyllysine-containing histones contain the negatively-charged aspartate or glutamate residues as part of the aromatic cage. Herein, we report thermodynamic analyses for the recognition of histone H3K4me3 and H3K4me2 by the tandem tudor domain of Sgf29 and its recognition site variants. Small uncharged and large aromatic substitutions on the Asp266 site resulted in a significant decrease in binding affinities for both H3K4me3 and H3K4me2, demonstrating the role of the negative charge of Asp266 in the readout process by Sgf29. This study emphasizes the essential contribution of electrostatic interactions to the overall binding affinity, and reveals that the underlying mechanisms for the recognition of Kme2/3 depend on the composition and arrangement of the aromatic cage.


Improved apparatus for spinal fluid cytomorphology.
The design of an apparatus for spinal fluid cytomorphology is described. It represents an improvement over previous devices using the enhanced sedimentation principle and has given reliable clinical results over a three year period.


Cerebellar modulation of the reward circuitry and social behavior.
The cerebellum has been implicated in a number of nonmotor mental disorders such as autism spectrum disorder, schizophrenia, and addiction. However, its contribution to these disorders is not well understood. In mice, we found that the cerebellum sends direct excitatory projections to the ventral tegmental area (VTA), one of the brain regions that processes and encodes reward. Optogenetic activation of the cerebello-VTA projections was rewarding and, in a three-chamber social task, these projections were more active when the animal explored the social chamber. Intriguingly, activity in the cerebello-VTA pathway was required for the mice to show social preference in this task. Our data delineate a major, previously unappreciated role for the cerebellum in controlling the reward circuitry and social behavior.


Management of the clinically negative neck in early-stage head and neck cancers after transoral resection.
The decision regarding treatment of the clinically negative neck has been debated extensively. This is particularly true with early-stage tumors for which surgery is the treatment of choice, and the tumor has been resected transorally without a cervical incision. Elective neck dissection in this situation is an additional procedure with potential associated morbidity. The alternative strategy for the clinically negative neck is to "wait and watch." Both an elective neck dissection policy and a "watchful waiting" policy have their proponents. The purpose of this article was for us to review the literature about this subject to try to answer the following question: if the tumor has been resected transorally, should an elective treatment of the neck be performed or is a "watchful waiting" policy safe and adequate? We conclude that, currently, the best available evidence suggests that elective neck dissection does not seem to be superior to the policy of observation without neck surgery, with regard to survival and control of neck disease. This review highlights the need for further well-designed prospective studies that will provide more reliable answers to the debatable issue of the management of the clinically negative neck in such cases.


Role in translation of a triple tandemly repeated sequence in the 5'-untranslated region of human thymidylate synthase mRNA.
A triple tandem repeat (TTR) consisting of 90 nucleotides exists immediately upstream of the ATG initiator codon in human thymidylate synthase (TS) cDNA (pcHTS-1). To investigate the role of the TTR in the expression of the TS cDNA, we used pcHTS-1 to construct mutant cDNA clones in which part of the TTR was deleted or an additional element was inserted. The mutant cDNA plasmid was introduced into murine TS-negative mutant cells and the relative translation efficiencies of the mutant cDNAs were determined by measuring the transient expression of TS activity and the amount of TS mRNA transcribed. The translation efficiency in transient expression of the mutants was increased by deletions covering all the first two repeated elements, and the part of the third closest to the ATG initiator codon, but was not affected by deletions of only parts of the first two repeated elements at the 5' end. The translation efficiency was also not affected by insertion of an additional repeated element into the TTR. These results suggest that the first two repeated elements at the 5' end both have inhibitory effects on translation of the TS mRNA, probably due to the unique structural feature of this element.


Identification and characterization of (GA/CT)n-microsatellite loci from Quercus petraea.
In this study a size selected genomic library from Quercus petraea was screened for (GA/CT)n-microsatellite sequences. The resulting loci were analysed by PCR for their usefulness as molecular markers in Q. petraea and Q. robur. 17 out of 52 tested primer pairs resulted in the amplification of a polymorphic single-locus pattern. The number of alleles found per locus varied from 6 to 16. Combining the genetic variation observed for the characterized loci provides a unique genotype for all the individuals tested. Using intraspecific controlled crosses of Q. robur trees Mendelian inheritance could be shown for five loci.


Inhibition of Aurora kinase B is important for biologic activity of the dual inhibitors of BCR-ABL and Aurora kinases R763/AS703569 and PHA-739358 in BCR-ABL transformed cells.
ABL tyrosine kinase inhibitors (TKI) like Imatinib, Dasatinib and Nilotinib are the gold standard in conventional treatment of CML. However, the emergence of resistance remains a major problem. Alternative therapeutic strategies of ABL TKI-resistant CML are urgently needed. We asked whether dual inhibition of BCR-ABL and Aurora kinases A-C could overcome resistance mediated by ABL kinase mutations. We therefore tested the dual ABL and Aurora kinase inhibitors PHA-739358 and R763/AS703569 in Ba/F3- cells ectopically expressing wild type (wt) or TKI-resistant BCR-ABL mutants. We show that both compounds exhibited strong anti-proliferative and pro-apoptotic activity in ABL TKI resistant cell lines including cells expressing the strongly resistant T315I mutation. Cell cycle analysis indicated polyploidisation, a consequence of continued cell cycle progression in the absence of cell division by Aurora kinase inhibition. Experiments using drug resistant variants of Aurora B indicated that PHA-739358 acts on both, BCR-ABL and Aurora Kinase B, whereas Aurora kinase B inhibition might be sufficient for the anti-proliferative activity observed with R763/AS703569. Taken together, our data demonstrate that dual ABL and Aurora kinase inhibition might be used to overcome ABL TKI resistant CML.


Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily member.
Human CD38 is a cell surface molecule involved in the regulation of lymphocyte adhesion to endothelial cells. This suggests that HUVEC bear a ligand(s) for CD38 on the cell surface. By means of the mAb Moon-1, which specifically inhibits CD38-mediated cell adhesion, we have identified a trans-membrane 130-kDa molecule acting as a ligand for CD38. Here, we report that the molecule recognized by the Moon-1 mAb is CD31, a member of the Ig superfamily. This conclusion is based on 1) cross-inhibition assays between Moon-1 and reference anti-CD31 mAbs; 2) sequential immunoprecipitation experiments using Moon-1 and known anti-CD31 mAbs, and 3) reactivity of the Moon-1 mAb with CD31 transfectants. Further, CD31 and CD38 cognate interactions were found to modulate heterotypic adhesion as well as to implement cytoplasmic calcium fluxes identical to those obtained by means of agonistic anti-CD38 mAbs. Other effects tested included the synthesis of messages for a panel of cytokines, markedly increased upon receptor-ligand interactions. These results suggest that the interplay between CD38 and its ligand CD31 is an important step in the regulation of cell life and of the migration of leukocytes (and CD38+ cancer cells) through the endothelial cell wall.


A critical evaluation of glucocorticoids in the management of severe COVID-19.
The viral infection by SARS-CoV-2 has irrevocably altered the life of the majority of human beings, challenging national health systems worldwide, and pushing researchers to rapidly find adequate preventive and treatment strategies. No therapies have been shown effective with the exception of dexamethasone, a glucocorticoid that was recently proved to be the first life-saving drug in this disease. Remarkably, around 20 % of infected people develop a severe form of COVID-19, giving rise to respiratory and multi-organ failures requiring subintensive and intensive care interventions. This phenomenon is due to an excessive immune response that damages pulmonary alveoli, leading to a cytokine and chemokine storm with systemic effects. Indeed glucocorticoids' role in regulating this immune response is controversial, and they have been used in clinical practice in a variety of countries, even without a previous clear consensus on their evidence-based benefit.


[Evolution of Neisseria meningitidis sensitivity to various antimicrobial drugs over the course of chemoprophylaxis during an epidemic outbreak].
The aim of this study was to assess the evolution of the population MICs for various antimicrobial drugs against Neisseria meningitidis isolates obtained from asymptomatic carriers during a chemoprophylaxis campaign carried out for an epidemic outbreak of meningococcal disease in Nerva, a small town in Huelva province (Spain). A nasopharyngeal carrier study including 427 people was carried out to determine the incidence rate of the epidemic strain among the general population. On the basis of the results, chemoprophylaxis with rifampicin was administered to the population aged 15 to 29 years (age group showing the highest incidence of the epidemic strain among carriers) living in Nerva. Three months later a new carrier study was performed (507 people) to evaluate the effects of chemoprophylaxis. Given the evolution of the outbreak, seven months later a new intervention was required with ciprofloxacin chemoprophylaxis; a second carrier study (399 people) was performed two months later to evaluate its effect. The number of strains isolated during the three carrier studies was 59 (13.8%), 33 (6.5%), and 22 (5.5%), respectively. Analysis of the changes in the MIC50 and MIC90 for the various antibiotics from the first to the second carrier study (rifampicin chemoprophylaxis) showed statistical differences only in the distribution of rifampicin MICs. Similarly, when changes from the second to the third study were analyzed (ciprofloxacin chemoprophylaxis), significant variations were detected for the cefotaxime MICs. Nevertheless, although there were changes in the MICs, the percentages of susceptibility from the beginning to the end of the study did not vary. Massive chemoprophylaxis in the age group with the highest incidence of the epidemic strain among carriers did not clearly modify the antibiotic susceptibility of the isolates. However, a slight increase in the MIC50 and MIC90 was observed for rifampicin after the first chemoprophylactic intervention and for cefotaxime at the end of the study. Consecutive chemoprophylactic interventions with rifampicin and ciprofloxacin had an impact on the percentage of meningococcal carriers in the overall population, with a clearly decreasing trend.


Amine-selective affinity resins based on pH-sensitive reversible formation of covalent bonds.
A new class of affinity resins using reversible covalent bonds is introduced for the separation of amine-containing molecules. pH-sensitive reversible formation of amic acid bonds between amines and carboxylate dimethyl maleic anhydride-decorated wrinkled silica nanoparticle resins was used to selectively retain and release amine-containing molecules, by controlling the pH.


An investigation of biodiesel production from wastes of seafood restaurants.
This work illustrates a comparative study on the applicability of the basic heterogeneous calcium oxide catalyst prepared from waste mollusks and crabs shells (MS and CS, resp.) in the transesterification of waste cooking oil collected from seafood restaurants with methanol for production of biodiesel. Response surface methodology RSM based on D-optimal deign of experiments was employed to study the significance and interactive effect of methanol to oil M : O molar ratio, catalyst concentration, reaction time, and mixing rate on biodiesel yield. Second-order quadratic model equations were obtained describing the interrelationships between dependent and independent variables to maximize the response variable (biodiesel yield) and the validity of the predicted models were confirmed. The activity of the produced green catalysts was better than that of chemical CaO and immobilized enzyme Novozym 435. Fuel properties of the produced biodiesel were measured and compared with those of Egyptian petro-diesel and international biodiesel standards. The biodiesel produced using MS-CaO recorded higher quality than that produced using CS-CaO. The overall biodiesel characteristics were acceptable, encouraging application of CaO prepared from waste MS and CS for production of biodiesel as an efficient, environmentally friendly, sustainable, and low cost heterogeneous catalyst.


Advancing rehabilitation research: an interactionist perspective to guide question and design.
The purpose of this position statement is to propose an interactionist framework to bring together the existing literature and provide a unifying direction for rehabilitation research. The framework comprises three components: the conceptual model, the research question, and the research design. The interactionist conceptual model has been adapted from the World Health Organization International Classification of Functioning, Disability, and Health. The model forms the starting point that guides the specification of the research question, which, in turn, guides the selection of research design. This approach demands that the question takes precedence and that there be an extensive repertoire of research designs, each of which is valued for its 'goodness-of-fit' with the question, rather than an a priori, single hierarchical ordering of designs. Research designs must be appropriate for questions that examine the disability experience, development over the lifespan, multifaceted interventions, low incidence conditions, and development of new interventions. Analytical challenges include dealing with confounding, mediating, and moderating variables. Rehabilitation researchers--and those who fund their work--should consider and value the use of diverse research methods to best answer the questions posed from the interactionist perspective.


miR-1207-5p regulates the sensitivity of triple-negative breast cancer cells to Taxol treatment via the suppression of LZTS1 expression.
Taxol-based chemotherapy is a conventional therapeutic approach for the treatment of triple-negative breast cancer (TNBC). However, the insensitivity of TNBC cells to Taxol greatly limits the anticancer effect of the drug and leads to patient mortality. The present study first evaluated the expression levels of microRNA (miR)-1207-5p in human normal breast epithelial MCF-10A cells and TNBC cell lines (MDA-MB-231, MDA-MB-436 and MDA-MB-453). The results revealed that the highest miR-1207-5p level was in MDA-MB-231, which suggested an oncogenic role of miR-1207-5p in TNBC. Therefore, MDA-MB-231 served as the present study's research model in subsequent experiments. The mRNAs that functioned as tumor suppressor factors for miR-1207-5p were then determined. Leucine zipper tumor suppressor gene 1 (LZTS1), which was predicted by TargetScan 6.2 and was supported by the results of a dual luciferase assay, was identified as a target of miR-1207-5p. AntagomiR-1207-5p increased LZTS1 mRNA and protein expressions, enhanced cell growth arrest and cell apoptosis induced by Taxol in MDA-MB-231 cells. Additionally, it was observed that, when compared with Taxol treatment, the combination of Taxol and antagomiR-1207-5p induced a sharp decrease in B-cell lymphoma 2 (Bcl-2) and phosphorylated-protein kinase B expression accompanied by an increase in the Bcl-2-associated X protein expression. Finally, miR-1207-5p expression was significantly increased, while LZTS1 expression was significantly decreased, in TNBC tissues when compared with normal adjacent tissues, and there was a negative correlation between miR-1207-5p and LZTS1 expression. In addition, there was a notable elevation in the expression of miR-1207-5p and a reduction in the expression of LZTS1 in the Taxol non-responsive TNBC tissues when compared with the Taxol-responsive TNBC tissues. The results of the present study suggested that miR-1207-5p may be a promising predictor of sensitivity towards Taxol in TNBC.


High-speed eight-channel thermocouple amplifier.
An eight-channel thermocouple amplifier system was constructed to measure rapid changes in temperature of only 1 or 2 degrees C simultaneously from many sites within the heart. The system has a response time of less than 5 ms, a resolution of less than 0.025 degrees C, and a voltage gain of approximately 2,500.


Proinflammatory cytokines induce amelotin transcription in human gingival fibroblasts.
Amelotin (AMTN) is a secreted protein transcribed predominantly during the maturation stage of enamel formation and localized in the junctional epithelium. We investigated differences in the levels of AMTN gene expression between non-inflamed gingiva and inflamed gingiva from patients with chronic periodontitis. Total RNAs were isolated from these tissues and their gene expression profiles were monitored by DNA microarray. The observed induction of AMTN mRNA in inflamed gingiva and cultured human gingival fibroblasts (HGF) was confirmed by real-time PCR. Transient transfection assays were performed using chimeric constructs of mouse AMTN gene promoter fragments linked to a luciferase reporter gene. Immunohistochemical localization of AMTN in inflamed and non-inflamed gingiva was assessed by immunohistochemistry. Among many differentially expressed genes, the level of AMTN mRNA was significantly increased in inflamed gingiva. Treatment of HGF with interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) induced the expression of AMTN mRNA, and increased the luciferase activities of the AMTN promoter constructs. AMTN protein was detected in inflamed gingival connective tissue and junctional epithelium. These findings demonstrate that proinflammatory cytokines induce AMTN gene expression in human gingival fibroblasts and suggest a role for AMTN in gingival inflammation.


Technical note: A histochemical approach in diagnosing hanging mechanical asphyxia on cadavers undergoing advanced putrefactive phenomena.
The authors used a particular protocol on putrefied corpses to highlight the cutaneous furrow. Two groups of cadavers were selected: in the first group (suicide by hanging mechanical asphyxia), the authors sampled cutaneous lozenges on the furrow still macroscopically recognisable, while in the second group (corpses deceased by different means), we sampled cutaneous lozenges in the hypostatic leaning. All specimens were divided in two: one underwent standard fixation while the other, previously rehydrated in Sandison's solution, was then fixed in formalin. All specimens were stained with hematoxylin and eosin and Resorcin-Fuchsin. Samples processed with formalin and the H&E staining underlined various artifacts; vice versa, the Sandison solution associated with Resorcin-Fuchsin staining demonstrated the compression of the elastic fibres, with focal positivity in hanged corpses, and diffuse positivity in the entire hypostatic leaning. Sandison's rehydrating solution and Resorcin-Fuchsin staining exalt the supposed application of an asphyctic mean even on putrefied corpses in those cases burdened by a diagnostic doubt.


Xylanase supplementation of pelleted wheat-based diets increases growth efficiency and apparent metabolizable energy and decreases viscosity of intestinal contents in broilers.
This study was designed to test graded supplementation of a thermostable xylanase in pelleted, wheat-based diets fed to broiler chickens over a 28-d period. A total of 600 Ross 708 male broilers were allotted to 1 of 5 dietary treatments: positive control (PC), negative control (NC; 125 kcal of AME/kg diet reduction relative to PC), and NC supplemented with 10, 15, or 30 g/ton of xylanase. Wheat-soybean meal-based diets were pelleted and fed in 2 feeding phases (14-d each). Study outcomes included growth performance, AME, and ileal digesta viscosity with 20 battery cages of 6 birds per treatment. Data were analyzed by 1-way ANOVA along with estimation of Pearson correlation coefficients. Whereas no difference between NC and PC was observed for BW gain, NC birds exhibited increased (P < 0.05) feed intake during each feeding phase and overall, which caused improvements (P < 0.05) in feed conversion ratio (FCR) for PC vs. NC birds. The analyzed AME of PC birds was 112 kcal/kg of diet greater (P < 0.05) than for NC birds, though no differences in digesta viscosity were observed. Xylanase supplementation of the NC diet at 15 or 30 g/ton elicited overall improvements (P < 0.05) in BW gain beyond the PC, while the 30 g/ton level equalized feed intake with the PC. Regardless of level, xylanase supplementation improved (P < 0.05) the FCR relative to the NC, thereby equalizing the response with the PC. Similarly, supplementation with any xylanase level increased (P < 0.05) AME over the NC, making all treatments synonymous with the PC. Digesta viscosity of all xylanase-supplemented treatments was decreased relative to both the NC and PC treatments. Overall, this study provided clear evidence that addition of a thermostable xylanase to pelleted wheat-based diets elicited improvements in growth performance of broilers concomitant with a reduction in digesta viscosity and elevation of analyzed dietary AME content.


Short-term effects of atropine combined with orthokeratology (ACO) on choroidal thickness.
To analyse the one-month change in subfoveal choroidal thickness (SFChT) of myopic children treated with 0.01 % atropine, orthokeratology (OK), or their combination. This is a prospective, randomized controlled trial. One hundred fifty-four children aged between 8 and 12 years with a spherical equivalent (SE) of -1.00 to -6.00 diopters were enrolled. Subjects were randomly assigned to receive 0.01 % atropine and orthokeratology (ACO, n = 39), 0.01 % atropine and single vision glasses (atropine, n = 42), orthokeratology and placebo (OK, n = 36), or placebo and single vision glasses (control, n = 37). SFChT was assessed using optical coherence tomography (OCT). Ocular parameters, including axial length (AL), were measured using a Lenstar LS 900. SFChT significantly increased in the ACO (14.12 ± 12.88 μm, p < 0.001), OK (9.43 ± 9.14 μm, p < 0.001) and atropine (5.49 ± 9.38 μm, p < 0.001) groups, while it significantly decreased in the control group (-4.81 ± 9.93 μm, p = 0.006). The one-month change in SFChT was significantly different between the control and treatment groups (p < 0.001). The results of pairwise comparisons among the treatment groups showed that the magnitude of the SFChT change was larger in the ACO group than in the atropine group (p = 0.002). The changes in the ACO and OK groups were not significantly different (p = 0.326). The combination of OK and atropine induced a greater increase in SFChT than monotherapy with atropine, which might indicate a better treatment effect for childhood myopia control.


Homeostatic Regulation of Astrocytes by Visual Experience in the Developing Primary Visual Cortex.
During postnatal development, sensory experience shapes the organization and function of cortical circuits. Previous studies focusing on experience-dependent plasticity of neurons have revealed a variety of mechanisms underlying cortical circuit rewiring. Emerging evidence shows that astrocytes play important roles in shaping cortical circuits through extensive interactions with different types of neurons and other glia cells. However, it remains unclear how astrocytes respond to sensory experience during postnatal development. In the present study, we profiled the maturation of astrocytes in the primary visual cortex (V1) at different postnatal stages. We then investigated the anatomical and physiological changes of astrocytes in V1 induced by multiple types of visual experience within 4 postnatal weeks. Compared with monocular deprivation during the critical period, binocular deprivation showed stronger impact on reactive astrocytes in V1. Moreover, long-term binocular deprivation significantly reduced the density of reactive astrocytes in layer 2/3 of V1 while strengthening gap junction couplings between astrocytes at the same time. Therefore, our data demonstrated that cortical astrocytes could undergo homeostatic plasticity in response to long-term changes of sensory inputs. The plasticity of astrocytes may interact with the plasticity of neurons to cooperatively shape cortical circuit refinement during postnatal development.


Von Recklinghausen's disease associated with malignant peripheral nerve sheath thmor presenting with constipation and urinary retention: a case report and review of the literature.
A malignant peripheral nerve sheath tumor (MPNST) is a rare neoplasm arising from peripheral nerve sheaths. We herein report the first case of MPNST originating from the left gluteal muscle region, diffusely extending into the adjacent small pelvis and perineum. The patient was a 25-year-old man who presented with symptoms of progressive constipation and urinary retention associated with weight loss. The patient had a family history of neurofibromatosis type 1. Physical examination showed numerous cafe-au-lait spots and sessile cutaneous neurofibromas. A computed tomography scan revealed a giant tumor which displaced the bladder and segments of the intestine. The histopathological diagnosis was MPNST. The mass was considered inoperable and palliative colostomy was performed. The patient declined chemotherapy and radiation therapy and died 2 months later.


The role of inflammasomes in cutaneous pathology.
Inflammasomes are large intracellular multiprotein complexes, which constitute a novel part of the innate immune system. In response to danger signals from pathogens or other harmful agents, inflammasomes assemble resulting in production of the inflammatory cytokines. We discuss recent knowledge of the role of deregulated inflammasome activity in skin pathologies such as autoinflammatory diseases as well as common skin diseases such as psoriasis and atopic dermatitis. We also present an insight into the activation and effector mechanisms of inflammasomes in skin carcinogenesis. The complex influence of inflammasome on cutaneous disorders raises new challenges and opportunities for the treatment of skin diseases.


Neural correlates of binocular depth inversion illusion in antipsychotic-naïve first-episode schizophrenia patients.
Binocular depth inversion illusion (BDII), a visual, 'top-down'-driven information process, is impaired in schizophrenia and particularly in its early stages. BDII is a sensitive measure of impaired visual information processing and represents a valid diagnostic tool for schizophrenia and other psychotic disorders. However, neurobiological underpinnings of aberrant BDII in first-episode schizophrenia are largely unknown at present. In this study, 22 right-handed, first-episode, antipsychotic-naïve schizophrenia patients underwent BDII assessment and MRI scanning at 1.5 T. The surface-based analysis via new version of Freesurfer (6.0) enabled calculation of cortical thickness and surface area. BDII total and faces scores were related to the two distinct cortical measurements. We found a significant correlation between BDII performance and cortical thickness in the inferior frontal gyrus and middle temporal gyrus (p < 0.003, Bonferroni corr.), as well as superior parietal gyrus, postcentral gyrus, supramarginal gyrus, and precentral gyrus (p < 0.05, CWP corr.), respectively. BDII performance was significantly correlated with surface area in the superior parietal gyrus and right postcentral gyrus (p < 0.003, Bonferroni corr.). BDII performance may be linked to cortical thickness and surface area variations in regions involved in "adaptive" or "top-down" modulation and stimulus processing, i.e., frontal and parietal lobes. Our results suggest that cortical features of distinct evolutionary and genetic origin differently contribute to BDII performance in first-episode, antipsychotic-naïve schizophrenia patients.


[Polygraphic recording of tremor and of hypertonic phenomena. Application to the action of various drugs].
The recording technique described makes possible the detailed analysis of hypertonia and tremor in Parkinson's disease, as well as the action of different drugs. It may contribute to the understanding of the physiopathological basis of these motor disturbances and the mode of action of anti-parkinsonian drugs. It also represents a reliable method of repeated observation, independent of subjective factors, in the evaluation of the long-term effectiveness of a medication. We were particularly concerned with the evaluation and comparison of the effect of different drugs in the course of a short study, involving the administration of a single dose of the medications used. In this way were studied: Apomorphine, given sub-cutaneously in non-emetic doses, which decreases in a constant and spectacular fashion both tremor and hypertonia ; Piribedil (1-3 mg IV) ; L-Dopa (100 mg IV) ; Ro-080576/007 F in a dose of one capsule containing 200 mg of L-Dopa and 50 mg of L-dopa-decarboxylase inhibitor. The effect of these various medications was invariable greater than that of a placebo and lasted much longer. With these doses, and under the special experimental conditions of this study, Piribedil was better tolerated and in general more active than L-dopa, in particular in relation to tremor. The action observed in the course of this short study prior to treatment might, to a certain extent, make it possible to predict the effect of long-term treatment.


Intestinal microbiome in scleroderma: recent progress.
Our evolving understanding of how gut microbiota affects immune function and homeostasis has led many investigators to explore the potentially pathologic role of gut microbiota in autoimmune diseases. This review will discuss the rapidly advancing field of microbiome research in systemic sclerosis (SSc), an incurable autoimmune disease with significant gastrointestinal morbidity and mortality. Recent reports have identified common perturbations in gut microbiota across different SSc cohorts. Compared with healthy controls, patients with SSc have decreased abundance of beneficial commensal genera (e.g. Faecalibacterium, Clostridium and Bacteroides) and increased abundance of pathbiont genera (e.g. Fusobacterium, Prevotella and Erwinia). Certain genera may protect against (e.g. Bacteroides, Clostridium, and Lactobacillus), or conversely exacerbate (e.g. Fusobacterium and Prevotella) gastrointestinal symptoms in SSc. These genera represent potential targets to avert or treat gastrointestinal dysfunction in SSc. Emerging evidence suggests that alterations in gut microbiota exist in the SSc disease state; however, future basic and clinical studies are needed to ascertain the mechanism by which these alterations perpetuate inflammation and fibrosis in SSc. Therapeutic trials are also needed to investigate whether dietary interventions or fecal transplantation can restore the gut microbial balance and improve health outcomes in SSc. VIDEO ABSTRACT: http://links.lww.com/COR/A38.


Gallstone expectoration following laparoscopic cholecystectomy.
Laparoscopic cholecystectomy is the treatment of choice for uncomplicated gallstone disease. Laparoscopic cholecystectomy may result in lost (spilled) gallstones. Such stones may precipitate various infective intra-abdominal complications. An unusual case of spilled gallstones eroding the diaphragm and eventually being expectorated out 12 months after laparoscopic cholecystectomy is reported.


The role of insulin resistance in experimental diabetic retinopathy-Genetic and molecular aspects.
Diabetic retinopathy is characterized by defects in the retinal neurovascular unit. The underlying mechanisms of impairment-including reactive intermediates and growth-factor dependent signalling pathways and their possible interplay are incompletely understood. This study aims to assess the relative role of hyperglycemia and hyperinsulinemia alone or in combination on the gene expression patterning in the retina of animal models of diabetes. As insulinopenic, hyperglycemic model reflecting type 1 diabetes, male STZ-Wistar rats (60mg/kg BW; i.p. injection at life age week 7) were used. Male obese ZDF rats (fa/fa) were used as type-2 diabetes model characterized by persisting hyperglycemia and transient hyperinsulinemia. Male obese ZF rats (fa/fa) were used reflecting euglycemia and severe insulin resistance. All groups were kept till an age of 20 weeks on respective conditions together with appropriate age-matched controls. Unbiased gene expression analysis was performed per group using Affymetrix gene arrays. Bioinformatics analysis included analysis for clustering and differential gene expression, and pathway and upstream activator analysis. Gene expression differences were confirmed by microfluidic card PCR technology. The most complex genetic regulation in the retina was observed in ZDF rats with a strong overlap to STZ-Wistar rats. Surprisingly, systemic insulin resistance alone in ZF rats without concomitant hyperglycemia did not induce any significant change in retinal gene expression pattern. Pathway analysis indicate an overlap between ZDF rats and STZ-treated rats in pathways like complement system activation, acute phase response signalling, and oncostatin-M signalling. Major array gene expression changes could be confirmed by subsequent PCR. An analysis of upstream transcriptional regulators revealed interferon-γ, interleukin-6 and oncostatin-M in STZ and ZDF rats. CONCLUSIONS: Systemic hyperinsulinaemia without hyperglycemia does not result in significant gene expression changes in retina. In contrast, persistent systemic hyperglycemia boosts much stronger expression changes with a limited number of known and new key regulators.


Importance of glucose-6-phosphate dehydrogenase activity for cell growth.
The intracellular redox potential, which is determined by the level of oxidants and reductants, has been shown to play an important role in the regulation of cell growth. The principal intracellular reductant is NADPH, which is mainly produced by the pentose phosphate pathway through the actions of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, and by 6-phosphogluconate dehydrogenase. Previous research has suggested that an increase in G6PD activity is important for cell growth. In this article, we suggest that G6PD activity plays a critical role in cell growth by providing NADPH for redox regulation. The results show the following: 1) inhibition of G6PD activity abrogated growth factor stimulation of [3H]thymidine incorporation in all cell lines tested; 2) overexpression of G6PD stimulated cell growth, as measured by an increase in [3H]thymidine incorporations as compared with cells transfected with vector alone; 3) inhibition of G6PD caused cells to be more susceptible to the growth inhibitory effects of H2O2; 4) inhibition of G6PD led to a 30-40% decrease in the NADPH/NADP ratio; and 5) inhibition of G6PD inhibited cell anchorage and significantly decreased the growth-related stimulation of tyrosine phosphorylation.


Antinociceptive effects of the aqueous extract of Brugmansia suaveolens flowers in mice.
The infusion of Brugmansia suaveolens, popularly known as trombeteira or cartucheira, has been used to treat pain in Brazil. The present study was conducted to test for its antinociceptive effects using the abdominal-writhing, formalin, tail-flick, and hot-plate tests in mice. The aqueous extract from B. suaveolens flowers administered intraperitoneally at doses of 100 and 300 mg/kg body weight significantly inhibited acetic acid-induced abdominal constrictions. An increase in hot-plate latency was also observed in animals receiving both doses (100 and 300 mg/kg). In the formalin test, both doses from the aqueous extract inhibited the first (0-5 min) and second phase (20-25 min). Tail-flick assays demonstrated that treatment of animals with plant extract induced attenuation of the response. These results suggest that the aqueous extract from B. suaveolens flowers produced antinociceptive effects, as demonstrated in the experimental models of nociception in mice. This supports popular medicinal uses of this plant as an analgesic.


Risks of hyperthermia associated with hot tub or spa use by pregnant women.
There are a limited number of human studies linking hot tub or spa use during early pregnancy to increased risks for neural tube defects (NTDs) or spontaneous abortion. However, these data can be considered in the context of human studies that have demonstrated an association between high maternal fever in early pregnancy and NTDs. In addition, there is a large volume of animal literature suggesting that, regardless of the heat source, an elevated core maternal temperature at or above the threshold of 2 degrees C over baseline, as well as timing and duration of exposure, are the critical factors in conferring risk. Therefore, the potential for hot tub or spa use to increase core maternal body temperature to risky levels and thus increase the risk for NTDs is likely. A woman who knows or who may not yet be aware that she is pregnant should be advised of the recommended limits of exposure. She should also be aware of the possible variability in hot tub or spa temperature readings and be able to accurately monitor maximum water temperature in the hot tub or spa so that her body temperature can be maintained below 38.9 degrees C.


Insight into high myopia and the macula.
The incidence of myopia is constantly on the rise. Patients of high myopia and pathological myopia are young and can lose vision due to a number of degenerative changes occurring at the macula. With the emergence of new technologies such as swept-source optical coherence tomography (OCT) and OCT angiography, our understanding of macular pathology in myopia has improved significantly. New conditions such as myopic traction maculopathy have been defined. Early, noninvasive detection of myopic choroidal neovascularization and its differentiation from lacquer cracks is possible with a greater degree of certainty. We discuss the impact of these new exciting and promising technologies and management of macular pathology in myopia. Incorporation of OCT in the microscope has also improved macular surgery. New concepts such as fovea-sparing internal limiting membrane peeling have emerged. A review of literature and our experience in managing all these conditions are discussed.


Synovial osteochondromatosis in bilateral subacromial bursae.
Abstract We report a rare case of synovial osteochondromatosis in bilateral subacromial bursae. A 73-year-old man presented with sudden shoulder pain. Roentgenograms showed a large number of calcifications between the acromial processes, and a greater tuberosity on both sides. Surgery was performed to remove loose bodies from both sides. There were 11 in the right subacromial bursa, and 9 in the left. According to Milgram's staging system, this case was diagnosed as stage III. A follow-up examination 10 months after the operation found no recurrence, pain, or limitation of the range of motion on either side.


Hippocampal Synaptic Dysfunction in a Mouse Model of Huntington Disease Is Not Alleviated by Ceftriaxone Treatment.
Glutamate transporters, particularly glutamate transporter 1 (GLT-1), help to prevent the adverse effects associated with glutamate toxicity by rapidly clearing glutamate from the extracellular space. Since GLT-1 expression and/or function are reduced in many neurodegenerative diseases, upregulation of GLT-1 is a favorable approach to treat the symptoms of these diseases. Ceftriaxone, a β-lactam antibiotic reported to increase GLT-1 expression, can exert neuroprotective effects in a variety of neurodegenerative diseases; however, many of these diseases do not exhibit uniform brain pathology. In contrast, as a drug that readily crosses the blood-brain barrier, ceftriaxone administration is likely to increase GLT-1 levels globally throughout the neuroaxis. In Huntington disease (HD), low GLT-1 expression is observed in the striatum in postmortem tissue and animal models. While ceftriaxone was reported to increase striatal GLT-1 and ameliorate the motor symptoms in a mouse model of HD, the extrastriatal effects of ceftriaxone in HD are unknown. Using electrophysiology and high-speed imaging of the glutamate biosensor iGluSnFR, we quantified real-time glutamate dynamics and synaptic plasticity in the hippocampus of the Q175FDN mouse model of HD, following intraperitoneal injections of either saline or ceftriaxone. We observed an activity-dependent increase in extracellular glutamate accumulation within the HD hippocampus, which was not the result of reduced GLT-1 expression. Surprisingly, ceftriaxone had little effect on glutamate clearance rates and negatively impacted synaptic plasticity. These data provide evidence for glutamate dysregulation in the HD hippocampus but also caution the use of ceftriaxone as a treatment for HD.


Non-coding RNAs: a promising target for early metastasis intervention.
Metastases account for the overwhelming majority of cancer-associated deaths. The dissemination of cancer cells from the primary tumor to distant organs involves a complex process known as the invasion-metastasis cascade. The underlying biological mechanisms of metastasis, however, remain largely elusive. Recently, the discovery and characterization of non-coding RNAs (ncRNAs) have revealed the diversity of their regulatory roles, especially as key contributors throughout the metastatic cascade. Here, we review recent progress in how three major types of ncRNAs (microRNAs, long non-coding RNAs, and circular RNAs) are involved in the multistep procedure of metastasis. We further examine interactions among the three ncRNAs as well as current progress in their regulatory mechanisms. We also propose the prevention of metastasis in the early stages of cancer progression and discuss current translational studies using ncRNAs as targets for metastasis diagnosis and treatments. These studies provide insights into developing more effective strategies to target metastatic relapse.


Formation of extracellular lipoteichoic acid by oral streptococci and lactobacilli.
Examination of the culture fluids from a number of strains of oral streptococci and latobacilli has shown the presence of an erythrocyte-sensitizing antigen with the properties of lipoteichoic acid. The antigen was isolated from the culture fluids of Lactobacillus casei and Lactobacillus fermentum and characterized chemically and serologically, For other strains, serological evidence for the presence of lipoteichoic acid depends on the reactivity with antiserum specific for the glycerol phosphate backbone. The relative concentrations of the antigen in culture fluids from different organisms, in culture fluids from different stages of growth, and in extracts of organisms was estimated by determining the maximum dilution that fully sensitized erythrocytes; the culture fluid titer, which is the reciprocal of the dilution, varied from 4 to 320. Strains of Streptococcus mutans were generally characterized by a high level of extracellular lipoteichoic acid, the amount being greater than that detectable in cell extracts; this conclusion was confirmed by using the quantitative precipitin method. A high-molecular-weight fraction obtained from S. mutans BHT culture fluid was effective in sensitizing erythrocytes at a concentration of 1 mug/ml, compared with 2 mug/ml required for cellular lipoteichoic acid from L. casei. The detecting procedure depends on the teichoic acid sensitizing erythrocytes but, as shown with L. fermentum, low-molecular-weight nonsensitizing teichoic acid may also be present in culture fluid.


CAK, the p34cdc2 activating kinase, contains a protein identical or closely related to p40MO15.
The mitotic inducer p34cdc2 requires association with a cyclin and phosphorylation on Thr161 for its activity as a protein kinase. CAK, the p34cdc2 activating kinase, was previously identified as an enzyme necessary for this activating phosphorylation. We confirm here that CAK is a protein kinase and describe its purification over 13,000-fold from Xenopus egg extracts. We further show that CAK contains a protein identical or closely related to the previously identified Xenopus MO15 gene: p40MO15 copurifies with CAK, and an antiserum to p40MO15 specifically depletes cAK activity. CAK appears to be the only protein in Xenopus egg extracts that can activate complexes of either p34cdc2 or the closely related protein kinase, p33cdk2, with either cyclin A or cyclin B. The sequence similarity between p40MO15 and p34cdc2, and the approximately 200 kDa size of CAK, suggest that p40MO15 may itself be regulated by subunit association and by protein phosphorylations.


Surgical management of coronal and sagittal imbalance of the spine without PSO: a multicentric cohort study on compensated adult degenerative deformities.
Sagittal imbalance of severe adult degenerative deformities requires surgical correction to improve pain, mobility and quality of life. Our aim was a harmonic and balanced spine, treating a series of adult degenerative thoracolumbar and lumbar kyphoscoliosis by a non posterior subtraction osteotomy technique. We operated 22 painful thoracolumbar and lumbar compensated degenerative deformities by anterior (ALIF), extreme lateral (XLIF) and transforaminal (TLIF) interbody fusion and grade 2 osteotomy (SPO) to restore lumbar lordosis and mobilize the coronal curve. Two-stage surgery, first anterior and after 2 or 3 weeks posterior, was proposed when the Oswestry Disability Index (ODI) was equal to or greater than 50% and VAS more than 5. All patients were submitted to X-ray and clinical screening during pre, post-operative and follow-up periods. We performed 5 ALIFs, 39 XLIFs, 8 TLIFs, 32 SPOs. No major complications were recorded and complication rate was 18% after lateral fusion and 22.7% after posterior approach. Pelvic tilt, lumbar lordosis, sagittal vertical axis and thoracic kyphosis improved (p < 0.05). Clinical follow-up (mean 20.5; range 18-24) was satisfactory in all cases, except for two due to sacroiliac pain. Mean preoperative VAS was 7.7 (range 6-10), while ODI was 67% on average (range 50-78). After two-stage surgery, VAS and ODI decreased, respectively, to 2.4 (range 2-4) and 31% (range 25-45), while their values were 4 (range 2-6) and 35% (range 20-55) at the final follow-up. Current follow-up does not allow definitive conclusions. However, the surgical approach adopted in this study seems promising, improving balance and clinical condition of adult patients with a compensated sagittal degenerative imbalance of the thoracolumbar spine.


Diffusion control in an elementary protein folding reaction.
The cold-shock protein CspB (from Bacillus subtilis), a very small protein of 67 residues, folds extremely fast in a reversible N &lrharr; U two-state reaction. Both unfolding and refolding are strongly decelerated when the viscosity of the solvent is increased by adding ethylene glycol or sucrose. The folding of CspB thus seems to follow Kramers' model for reactions in which the reactants must diffuse together. It indicates that the compaction of the protein chain occurs in the rate-limiting step of folding. Chain diffusion to a productively collapsed form and the crossing of a high energy barrier are thus tightly coupled in this folding reaction, and the measured reaction rate depends on both the diffusion of the protein chain in the solvent and the magnitude of the activation energy. We suggest that in protein folding an energetic barrier is essential to separate the native from the unfolded conformations of a protein. This barrier protects the ordered structure of a native protein against continuous unfolding by diffusive chain motions and leads to apparent two-state behavior.


Activation of the TGF-beta/Smad signaling pathway in focal segmental glomerulosclerosis.
Although the pathogenetic relevance of transforming growth factor-beta (TGF-beta) to glomerulosclerosis is well established, it is not known whether a signal transduction cascade of TGF-beta is involved in the development of focal segmental glomerulosclerosis (FSGS), nor is it clear how TGF-beta 1 is activated during the course of FSGS formation. We examined the expression patterns of TGF-beta 1, thrombospondin-1 (TSP-1), TGF-beta type II receptor (TGF-beta IIR), phosphorylated Smad2/Smad3, and podocyte-specific epitopes [Wilms' tumor protein-1 (WT-1) and glomerular epithelial protein-1 (GLEPP-1)] in 15 renal biopsy specimens with idiopathic FSGS and six renal biopsies with no detectable abnormalities by means of immunohistochemistry. The mRNA expression patterns of TGF-beta 1, TGF-beta IIR, and TSP-1 were further evaluated by in situ hybridization in seven biopsies. In the controls, immunostaining for TGF-beta 1, TSP-1, TGF-beta IIR, and phosphorylated Smad2/Smad3 was almost negligible, but an apparent signal for TGF-beta 1, TSP-1, and TGF-beta IIR mRNAs was observed in the visceral glomerular epithelial cells (GEC). In the cases of FSGS, the expression levels of TGF-beta 1, TSP-1, and TGF-betaIIR proteins and mRNAs and phosphorylated Smad2/Smad3 were significantly increased, particularly in the GEC of the sclerotic segments, wherein WT-1 and GLEPP-1 were not detected. These results suggest that damage to podocyes may stimulate TGF-beta 1, TSP-1, and TGF-beta IIR expression in GEC, thereby activating the Smad signaling pathway and, in so doing, leading to overproduction of the extracellular matrix (ECM). Thus, a signal transduction cascade of the TGF-beta/Smad signaling pathway, which is activated in the GEC, appears to be involved in the development of FSGS.


Structural changes in 2-diarylthiophene-substituted starburst compounds upon charging: a theoretical and spectroelectrochemical study.
The role of charging in structural changes of 2-diarylaminothiophene-substituted starburst compounds is clarified by combining theoretical and spectroelectrochemical studies. A systematic and comparative theoretical calculation based on density functional theory and semiempirical Austin Model 1 (AM1) calculations is performed on the neutral and charged states of four model tris(5-diarylamino-5-thienyl)-terminated starburst compounds with a central triphenylamine and 1,3,5-triphenylbenzene moiety. Our results indicate that the charging of molecules leads to structural changes by quinoid-type components mostly on the dendrimers terminated by phenothiazinyl fragments. Based on the optimal geometries, the spectroscopic properties were calculated using the semiempirical Zerner's intermediate neglect overlap method. The presented theoretical results and the spin electron distributions of charged states and their spectra are supported by the spectroelectrochemical observations caused by the different electron localization within the studied molecules after charging. The satisfactory agreement between theoretical electronic transitions and experimental values indicates that a rational design of tunable molecular layers in organic devices based on the starburst compounds described is possible.


Protein Conformational Flexibility Enables the Formation of Dense Liquid Clusters: Tests Using Solution Shear.
According to recently proposed two-step nucleation mechanisms, crystal nuclei form within preexisting dense liquid clusters. Clusters with radii about 100 nm, which capture from 10(-7) to 10(-3) of the total protein, have been observed with numerous proteins and shown to host crystal nucleation. Theories aiming to understand the mesoscopic size and small protein fraction held in the clusters have proposed that in solutions of single-chain proteins, the clusters consist of partially misfolded protein molecules. To test this conjecture, we perturb the protein conformation by shearing solutions of the protein lysozyme. We demonstrate that shear rates greater than a threshold applied for longer than 1 h reduce the volume of the cluster population. The likely mechanism of the observed response involves enhanced partial unfolding of lysozyme molecules, which exposes hydrophobic surfaces between the constituent domains to the aqueous solution.


An orally delivered small-molecule formulation with antiangiogenic and anticancer activity.
Targeting angiogenesis, the formation of blood vessels, is an important modality for cancer therapy. TNP-470, a fumagillin analog, is among the most potent and broad-spectrum angiogenesis inhibitors. However, a major clinical limitation is its poor oral availability and short half-life, necessitating frequent, continuous parenteral administration. We have addressed these issues and report an oral formulation of TNP-470, named Lodamin. TNP-470 was conjugated to monomethoxy-polyethylene glycol-polylactic acid to form nanopolymeric micelles. This conjugate can be absorbed by the intestine and selectively accumulates in tumors. Lodamin significantly inhibits tumor growth, without causing neurological impairment in tumor-bearing mice. Using the oral route of administration, it first reaches the liver, making it especially efficient in preventing the development of liver metastasis in mice. We show that Lodamin is an oral nontoxic antiangiogenic drug that can be chronically administered for cancer therapy or metastasis prevention.


[Oral hygiene. KIGGS data on caries preventative behaviour].
The present analysis deals with the identification of populations at risk with regard to oral hygiene and the prevention of caries in children and adolescents in Germany. Using a written questionnaire, which constituted a part of the KIGGS Survey for children and adolescents, 17,641 participants aged between 0 to 17 years were asked about how frequently they brushed their teeth, and how often they had dental check-ups. During a standardised medical interview caries preventative medications were recorded. In consideration of socio-demographic factors, risk populations for insufficient dental hygiene and caries prophylaxis were identified by means of logistic regression. Determinants for insufficient dental hygiene are male sex (odds ratio (OR) 1.6), low social status (OR 2.2) and migrational background (OR 2.3). The social and culture-specific determinancy is also mirrored in the insufficient utilisation of dental check-ups. In addition, there are significant differences between East and West Germany (OR West 1.3) and urban residence (OR 1.9). Age (0-2 years OR 10.4), social and migrational status proved to be significant factors influencing use of tablet fluoridation. These results stress the necessity of preventative measures for these specific target groups to improve dental hygiene and health.


Temporal series analysis approach to spectra of complex networks.
The spacing of nearest levels of the spectrum of a complex network can be regarded as a time series. Joint use of the multifractal detrended fluctuation approach (MF-DFA) and diffusion entropy (DE) is employed to extract characteristics from this time series. For the Watts-Strogatz small-world model, there exists a critical point at rewiring probability P(r) =0.32. For a network generated in the range 0< P(r) <0.32, the correlation exponent is in the range of 1.0-1.64. Above this critical point, all the networks behave similar to that at p(r) =1. For the Erdos-Renyi model, the time series behaves like fractional Brownian motion noise at p(ER) =1/N. For the growing random network (GRN) model, the values of the long-range correlation exponent are in the range of 0.74-0.83. For most of the GRN networks the probability distribution function of a constructed time series obeys a Gaussian form. In the joint use of MF-DFA and DE, the shuffling procedure in DE is essential to obtain a reliable result.


CMTM5 exhibits tumor suppressor activities and is frequently silenced by methylation in carcinoma cell lines.
CMTM5 (CKLF-like MARVEL transmembrane domain containing member 5) is located at 14q11.2, a locus associated with multiple cancers. It has six RNA splicing variants with CMTM5-v1 as the major one. We explored its expression pattern in normal tissues and tumor cell lines, as well as its functions in carcinoma cells. We evaluated CMTM5 expression by semiquantitative reverse transcription-PCR (RT-PCR) in normal tissues and carcinoma cell lines of cervical, breast, nasopharyngeal, lung, hepatocellular, esophageal, gastric, colon, and prostate. We further examined CMTM5 promoter methylation in these cell lines. We also analyzed CMTM5 expression after 5-aza-2'-deoxycytidine treatment and genetic demethylation and the functional consequences of restoring CMTM5 in HeLa and PC-3 cells. CMTM5-v1 is broadly expressed in human normal adult and fetal tissues, but undetectable or down-regulated in most carcinoma cell lines. Its promoter methylation was detected in virtually all the silenced or down-regulated cell lines. The silencing of CMTM5 could be reversed by pharmacologic demethylation or genetic double-knockout of DNMT1 and DNMT3B, indicating methylation-mediated mechanism. Restoration of CMTM5-v1 suppressed carcinoma cell proliferation, migration, and invasion. These results indicate that CMTM5 exhibits tumor suppressor activities, but with frequent epigenetic inactivation in carcinoma cell lines.


Endoscopic endonasal surgery--concepts in treatment of recurring rhinosinusitis. Part II. Surgical technique.
Our endoscopic endonasal surgery, under the guidance of rigid endoscopes, aims at the primary focuses in the anterior ethmoid, clearing stenotic clefts and infected ethmoidal cells of diseased mucosa. The maxillary ostium is enlarged into the anterior nasal fontanelle to provide drainage and ventilation. There is no need for any fenestration into the inferior nasal meatus. Once the ethmoidal focus is cleared, the dependent larger sinuses usually heal without having been touched--even if their mucosal pathologies seemed almost irreversible. The endoscopic procedure, which except in children is carried out under local and surface anesthesia, is described in detail. Excellent results with this method, developed by Messerklinger, indicate that there is seldom need for a Caldwell-Luc operation as the state-of-the-art procedure in chronic recurring sinusitis.


Making of a Successful Early Mobilization Program for a Medical Intensive Care Unit.
To provide a guideline for intensive care unit (ICU) early mobilization program development and implementation and to describe the patient characteristics and endpoints for those who participated in our hospital's early mobilization program. An ICU early mobilization program was developed with five guiding principles: analgesia/sedation optimization, sedation minimization, protocol of progressive mobility, physical therapy and occupational therapy recruitment, and nursing education. This program began in April 2014, and the initial 32 patients who ambulated while receiving mechanical ventilation were retrospectively assessed and their characteristics described. After program implementation, more than 50 mechanically ventilated patients ambulated in the first year following early mobilization initiation. Patients with an FiO2 as high as 1.0 and on nonconventional modes of mechanical ventilation successfully ambulated without adverse events. The mean ambulation distance was 102 ± 152 f. and usually required three ICU staff members with 5 to 10 minutes of preparation before ambulation. After implementation, a retrospective analysis revealed a decrease in the average length of ICU stay, from 4.8 to 4.1 days. Addressing analgesia and sedation practices, along with instituting a progressive mobility protocol and recruiting physical and occupational therapy, may serve as a guide to the creation of a successful early mobilization program. This study provides additional supportive evidence that early mobilization in the ICU is safe and effective.


Cell-specific cyclic AMP-mediated induction of the PDGF receptor.
Cyclic AMP (cAMP) cooperates with a wide variety of polypeptide growth factors to synergistically stimulate the proliferation of many vertebrate cell types. However, the cellular mechanisms underlying these cooperative interactions are for the most part unknown. We have identified one such mechanism by observing that (i) cultured rat Schwann cells proliferate in response to platelet-derived growth factor (PDGF) only if simultaneously cultured in the presence of agents that elevate intracellular cAMP and (ii) this unmasked PDGF response is accounted for by a dramatic cAMP-mediated induction of PDGF receptor mRNA and protein. cAMP-mediated induction of the PDGF receptor results in enhanced, ligand dependent receptor autophosphorylation, and in enhanced PDGF activation of c-fos gene expression. In addition, this induction is unique to those cells, such as Schwann cells, for which cAMP is itself mitogenic. These results indicate that the synergistic proliferative effect obtained from the combination of cAMP and polypeptide growth factors may in large result from the cAMP-mediated induction of growth factor receptors.


USP39 promotes colorectal cancer growth and metastasis through the Wnt/β-catenin pathway.
In the present study, we first examined the expression of USP39 protein using tissue array containing 90 colorectal cancer (CRC) tissues and 9 clinical samples, and observed that it has significantly higher expression in cancer tissues as compared to the corresponding adjacent normal tissues. Also, we tested USP39 expression level in four CRC cancer cell lines and identified that it indeed had higher expression in all these CRC cell lines. In addition, its knockdown inhibited not only the cell growth of SW480 and HT29 cells, but also the cell migration and invasion. Further analysis of its molecular mechanism suggested that the expression of four crucial proteins of Wnt/β-catenin pathway, including β-catenin, TCF4, MMP2 and MMP9 was reduced as a result of USP39 knockdown. Taken together, all these findings demonstrated that USP39 protein plays an important role in the growth and metastasis of colorectal cancer mainly through Wnt/β-catenin pathway.


Activation of mesangial cells by platelets in systemic lupus erythematosus via a CD154-dependent induction of CD40.
Platelets are potential contributors to glomerular injury via the release of chemotactic and/or mitogenic mediators upon activation or through direct CD154/CD40-dependent interaction with cell components of the glomerulus. We examined whether platelets could activate mesangial cells and the potential role of the platelet-associated CD154. Thrombin-activated platelets from systemic lupus erythematosus (SLE) patients or from disease or healthy controls were grown with human mesangial cells in the presence or not of a neutralizing anti-CD154 antibody either in contact or in a noncontact setting, the platelets and mesangial cells being separated by a pore size semipermeable membrane. The induction of mesangial cell surface antigens was assayed by flow cytometry. The quantification of mesangial cell proliferation was performed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and the production of transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor (PDGF) and soluble CD40 were measured by enzyme-linked immunosorbent assay (ELISA). Activated platelets from patients with SLE could induce an up-regulation of the expression of CD40 on mesangial cells with a concomitant release of soluble CD40. This induction required a direct contact between platelets and mesangial cells and was dependent upon the platelet-associated CD154. Pathologic consequences of the up-regulation of CD40 were a CD40-dependent stimulation of the proliferation of mesangial cells and a CD40-dependent increased production of TGF-beta1 by these cells. Platelets from patients with SLE can activate mesangial cells through CD40/CD154 interactions, leading to an induction of proliferation of the mesangial cells and an enhanced production of TGF-beta1, a profibrotic cytokine.


Effects of promoter strengths and growth conditions on copy number of transcription-fusion vectors.
Promoters with widely different transcriptional activities have been fused to the galactokinase gene contained in a multicopy plasmid ( McKenny , K., Shimatake , H., Court, D., Schmeissner , U., Brady, C., and Rosenberg, M. (1982) in Gene Amplification and Analysis: Analysis of Nucleic Acids ( Chirkjian , J. G., and Papas , T., eds) pp. 383-415, Elsevier /North-Holland Biomedical Press, Netherlands). Assay methods which allow determination of galactokinase-specific activity (nanomoles of galactose 1-phosphate/min/mg of protein) and plasmid-specific number (femtomoles of plasmid/mg of protein) in the same sonicated cellular extract are described. These methods provide a way to accurately measure and compare the promoter activities (nanomoles of galactose 1-phosphate/min/fmol of plasmid) of different plasmid constructions which exhibit different in vivo plasmid copy numbers. It is demonstrated that in vivo, copy number fluctuations are correlated with such parameters as promoter strength and cellular growth conditions. The ability to account for these uncontrolled in vivo copy number variations when comparing the transcriptional activities of different DNA inserts in multicopy transcription-fusion plasmids greatly facilitates the utility of these systems.


[Value of bead-type cassettes for antibiograms of Streptococci in Autobac units].
Antimicrobial susceptibility testing of Streptococci in automated units (Autobac) is not always satisfactory: aggregates formed spontaneously by Streptococci in the medium used can reduce the reliability of tests by interfering with correct reading, and, in many cases, bacterial growth is very slow, necessitating long periods for analysis (up to 6 hours). Owing to the fact that use of "bead type" cassettes for antifungal susceptibility testing in the Autobac improved results, and in particular prevented the formation of aggregates, we decided to adopt the same system for tests of streptococci. Each compartment in these cassettes contains glass microbeads which prevent aggregate formation thanks to an agitation mechanism. Rapid sedimentation of these beads allows normal reading with the Autobac. A comparative study of 66 strains of streptococci with various antibiotics was performed. Three techniques were used: classical diffusion technique, susceptibility testing with the standard cassette in the Autobac, and test with the bead type cassette in the Autobac. Parameters evaluated included the effective duration of each test, and comparison of the results (Autobac with and without beads, diffusion method). Results are detailed and discussed.


Patient comfort during pelvic examination. New foot supports vs metal stirrups.
One hundred women patients at a midwestern university health center were randomly assigned to a control or experimental group to measure statistically comfort levels of new foot supports vs. traditional metal stirrups during pelvic examinations. Written comments were also obtained. Analyses using the t test demonstrated a significant positive change in attitude in the experimental group.


A Retrospective Analysis of Antithrombin III Replacement Therapy for the Treatment of Hepatic Sinusoidal Obstruction Syndrome in Children Following Hematopoietic Stem Cell Transplantation.
Hepatic sinusoidal obstruction syndrome (SOS) remains a serious complication of hematopoietic stem cell transplantation (HSCT). In this single institution retrospective case series, 18 children developed SOS after HSCT. Patients were treated with antithrombin III (ATIII), defibrotide, or ATIII followed by defibrotide. Twelve of 13 patients who were treated with ATIII therapy alone had complete resolution of SOS, including 4 of 5 children with severe SOS. In this limited cohort, ATIII was safe and successfully prevented progression of hepatic SOS following HSCT in the majority of children at our center.


Chemical probes of histone lysine methyltransferases.
Growing evidence suggests that histone methyltransferases (HMTs, also known as protein methyltransferases (PMTs)) play an important role in diverse biological processes and human diseases by regulating gene expression and the chromatin state. Therefore, HMTs have been increasingly recognized by the biomedical community as a class of potential therapeutic targets. High quality chemical probes of HMTs, as tools for deciphering their physiological functions and roles in human diseases and testing therapeutic hypotheses, are critical for advancing this promising field. In this review, we focus on the discovery, characterization, and biological applications of chemical probes for HMTs.


Preparation of an agar-silver nanoparticles (A-AgNp) film for increasing the shelf-life of fruits.
Preparation of protective coating possessing antimicrobial properties is present day need as they increase the shelf life of fruits and vegetables. In the present study, preparation of agar-silver nanoparticle film for increasing the shelf life of fruits is reported. Silver nanoparticles (Ag-NPs) biosynthesised using an extract of Ocimum sanctum leaves, were mixed with agar-agar to prepare an agar-silver nanoparticles (A-AgNp) film. This film was surface-coated over the fruits, Citrus aurantifolium (Thornless lime) and Pyrus malus (Apple), and evaluated for the determination of antimicrobial activity of A-AgNp films using disc diffusion method, weight loss and shelf life of fruits. This study demonstrates that these A-AgNp films possess antimicrobial activity and also increase the shelf life of fruits.


The maize chromosomal HMGa protein recognizes structural features of DNA and increases DNA flexibility.
The abundant maize high-mobility group protein HMGa belongs to the chromosomal, non-histone proteins and consists of a basic region containing the HMG-box DNA-binding domain and a highly acidic carboxy-terminal tail. The full-length HMGa protein and a truncated version lacking the acidic tail were synthesized in Escherichia coli and tested for their ability to induce DNA-bending in a ligase mediated circularization assay with short DNA fragments. It is shown that the recombinant HMGa protein as well as its truncated form efficiently cause circularization of the tested DNA fragments without an obvious requirement for stable DNA-binding. They bind furthermore preferentially to A/T-rich linear DNA or bent DNA structures such as four-way junctions and DNA minicircles. The DNA-binding properties and the ability to increase DNA flexibility suggest a general role of the HMGa protein in assisting the formation of nucleoprotein complexes, possibly by facilitating interactions of proteins bound to adjacent DNA sites.


Opioids Interfere With Deglutitive Inhibition Assessed by Response to Multiple Rapid Swallows During High-Resolution Esophageal Manometry.
Normal response to multiple rapid swallows (MRS) during high-resolution esophageal manometry is deglutitive inhibition; opioids may interfere with this. The aim of this study was to evaluate the response to MRS in patients on opioids, not on opioids, and healthy controls. Response to MRS was evaluated for complete vs impaired inhibition in 72 chronic opioid users, 100 patients not on opioids, and 24 healthy controls. Impaired deglutitive inhibition was significantly more frequent in chronic opioid users compared with patients not on opioids and healthy controls (54% vs 14% vs 0%; P < 0.0001). Impaired deglutitive inhibition during MRS is frequent in opioid users, supporting that opioids interfere with esophageal inhibitory signals.


Comparison of faecal bile acid profiles between patients with adenomatous polyps of the large bowel and healthy subjects in Japan.
Faecal bile acid excretion was examined in 13 patients with adenomatous polyps of the large bowel and compared with a series of matched healthy subjects. Bile acids were analysed in detail with respect to the composition of individual bile acids and their mode of conjugation. The total excretion of bile acids by the patient group and the healthy subjects ranged from 55.0-837.6 mumol/day (median 233.8, mean 346.9) and 93.8-712.3 mumol/day (median 489.2, mean 386.7) respectively. Expressed as mumol/g faecal weight these values were 0.6-4.8 (median 2.2, mean 2.4) and 0.4-5.8 (median 2.2, mean 2.8) and in terms of mumol/g faecal dry weight, 1.9-50.7 (median 10.1, mean 16.5) and 3.9-32.4 (median 16.3, mean 16.7) respectively for the two groups. The composition of the individual bile acids and their distribution within the various conjugate fractions was essentially the same for both groups. Cholenoic acid (5 beta-chol-3-enoic acid), an unusual bile acid, was detected in one patient and three healthy subjects. These results revealed no significant quantitative differences in bile acid excretion between the group of patients with adenomatous polyps and those of healthy subjects.


Genetic toxicity assessment: employing the best science for human safety evaluation. Part II: Performances of the in vitro micronucleus test compared to the mouse lymphoma assay and the in vitro chromosome aberration assay.
The in vitro micronucleus test is commonly used in the early stages of pharmaceutical development as a predictive tool for the regulatory mouse lymphoma assay or in vitro chromosome aberration test. The accumulated data from this assay leads to the suggestion that it could be used as an alternative to the chromosome aberration test or the mouse lymphoma assay in the regulatory genotoxicity battery. In this paper, we present the results of the in vitro micronucleus test on L5178Y mouse lymphoma cells with 25 compounds from Servier research and have compared these results to those obtained in the genotoxicity regulatory battery. All the negative compounds were also negative in the in vitro micronucleus assay. Among the 14 positive compounds, two of them, positive in the mouse lymphoma assay, were found negative in the in vitro micronucleus test. However, this apparent discordance was likely to be due to cytotoxicity- or high concentration-related false positive responses in the mouse lymphoma assay. In addition, we confirmed that the in vitro micronucleus assay is useful for detecting aneugens, especially, when cells in metaphasis and multinucleated cells are also scored and when cells are allowed to recover after the long treatment. On this series of compounds, the in vitro micronucleus assay showed high sensitivity and possibly a better specificity than the mouse lymphoma assay. Thus, the in vitro micronucleus assay was shown to be at least as adequate as the mouse lymphoma assay or the in vitro chromosome aberration test to be used in the standard genotoxicity battery.


Apoptotic cells in peripheral blood from patients with low serum cobalamin.
Apoptotic leukocytes were found by using ultrastructural and light microscopic techniques to examine peripheral blood in ten of twelve patients with low serum cobalamin (vitamin B12) and rarely in normal controls. A total of 88 apoptotic cells (.14% of total leukocytes) were identified in all the patients. One patient also had apoptotic cells found on a routine blood smear. There was no correlation between the finding of these cells and nuclear hypersegmentation, serum cobalamin levels, serum intrinsic factor antibody, serum methylmalonic acid and homocysteine or the Schilling test. Two patients, however, with the most severe vitamin deficiency did not have increased numbers of apoptotic cells suggesting that these patients had lost the ability to initiate the cell death program.


Anterograde Headless Cannulated Screw Fixation in the Treatment of Medial Malleolar Fractures: Evaluation of a New Technique and Its Outcomes.
To evaluate the functional and radiological outcomes of anterograde headless cannulated screw fixation for medial malleolar fractures. This study included 12 patients (8 males, 4 females; age 27-55 years) with medial malleolar type B fractures according to the Herscovici fracture classification who had undergone anterograde headless cannulated screw fixation surgery between 2012 and 2014. Seven had an isolated medial malleolar fracture and 5 a bimalleolar fracture. All of the bimalleolar fractures were classified as 44-B2 based on the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) classification. Postoperatively, bone union was evaluated on direct radiographs at the final follow-up examination. The American Orthopaedic Foot and Ankle Society (AOFAS) scoring system was used for clinical evaluation. The mean follow-up period was 17.2 ± 5.3 months (range 12-23). Full union was achieved in all fractures. The mean time to union was 3.4 ± 1.5 months (range 2-5). No instability, loss of reduction, non-union or infection was observed in any patient. The mean AOFAS score was 95.0 ± 5.4 (range 87-99). Based on the AOFAS score, 4 patients showed good results and 8 excellent results. The mean time to return to the previous level of activity was 4.0 ± 2.5 months (range 2-5). In this study, anterograde headless cannulated screw fixation yielded good clinical outcome in the surgical treatment of Herscovici type B fractures.


[The use of apoptosis inducers in the therapy of experimental influenza infection and preventing of chronic post-influenza lung damage].
Influenza is a respiratory infection widely spread around the world. Influenza complications are various in nature and in most cases involve the excessive proliferation of cells in respiratory tract as a factor of pathogenesis. In the present work the efficacy of the use of apoptosis inducer 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalenecarboxylic acid (AHPN) for prophylaxis of chronic damage on the stage of post- influenza pneumonia has been studied. Mice were infected with influenza virus A/mallard/Pennsylvania/10218/84(H5N2) with further study of the level of influenza virus reproduction in the lungs, specific mortality of animals and morphology of the foci of post-influenza pneumonia on the 15th day post inoculation. AHPN was shown to decrease the infectious activity of the virus in the lungs by 1.2-1.5 log10 EID50/0.2 mL depending on the dose as compared to the control group, in a weak decrease in mortality of animals (protection index was 12.5-37.5%). The application of AHPN restricted both the proliferative and infiltrative component in chronic post-influenza lesions. It demonstrated the most pronounced effect on the lung morphology when applied on days 4 to 7 post inoculation, i. e. in the period of maximal activation of inflammatory tissue infiltration and regeneration of bronchiolar epithelium. In conclusion, the use of apoptosis inducers can partially prevent the development of chronic post-influenza lesions with proliferative component.