bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of Human Immunodeficiency Virus-Derived Vectors with Wild-Type Virus in Transduced Cells
Authors: Bukovsky Anatoly A. , Song Jin-Ping , Naldini Luigi
Published: December 2019

The interaction of human immunodeficiency virus (HIV)-derived vectors with wild-type virus was analyzed in transduced cells. Vector transcripts upregulated by infection had no measurable effect on HIV type 1 (HIV-1) expression but competed efficiently for encapsidation, inhibiting the infectivity and spread of HIV-1 in culture and leading to mobilization and recombination of the vector. These effects were abrogated with a self-inactivating vector.
Unique Properties of the Large Antigen of Hepatitis Delta Virus
Authors: Moraleda Gloria , Seeholzer Steven , Bichko Vadim , Dunbrack Roland , Otto James , Taylor John
Published: December 2019

The large form of the hepatitis delta virus (HDV) protein (L) can be isoprenylated near its C terminus, and this modification is considered essential for particle assembly. Using gel electrophoresis, we separated L into two species of similar mobilities. The slower species could be labeled by the incorporation of [
14
C]mevalonolactone and is interpreted to be isoprenylated L (L
i
). In serum particles, infected liver, transfected cells, and assembled particles, 25 to 85% of L was isoprenylated. Isoprenylation was also demonstrated by
14
C incorporation in vitro with a rabbit reticulocyte coupled transcription-translation system. However, the species obtained migrated even slower than that detected by labeling in vivo. Next, in studies of HDV particle assembly in the presence of the surface proteins of human hepatitis B virus, we observed the following. (i) Relative to L, L
i
was preferentially assembled into virus-like particles. (ii) L
i
could coassemble the unmodified L and the small delta protein, S. (iii) In contrast, a form of L with a deletion in the dimerization domain was both isoprenylated and assembled, but it could not support the coassembly of S. Finally, to test the expectation that the isoprenylation of L would increase its hydrophobicity, we applied a phase separation strategy based on micelle formation with the nonionic detergent Triton X-114. We showed the following. (i) The unique C-terminal 19 amino acids present on L relative to S caused a significant increase in the hydrophobicity. (ii) This increase was independent of isoprenylation. (iii) In contrast, other, artificial modifications at either the N or C terminus of S did not increase the hydrophobicity. (iv) The increased hydrophobicity was not sufficient for particle assembly; nevertheless, we speculate that it might facilitate virion assembly.
Effect of Retreatment with Interferon Alone or Interferon plus Ribavirin on Hepatitis C Virus Quasispecies Diversification in Nonresponder Patients with Chronic Hepatitis C
Authors: Gerotto Martina , Sullivan Daniel G. , Polyak Stephen J. , Chemello Liliana , Cavalletto Luisa , Pontisso Patrizia , Alberti Alfredo , Gretch David R.
Published: December 2019

Alpha interferon (IFN-α) treatment is effective on a long-term basis in only 15 to 25% of patients with chronic hepatitis C. The results of recent trials indicate that response rates can be significantly increased when IFN-α is given in combination with ribavirin. However, a large number of patients do not respond even to combination therapy. Nonresponsiveness to IFN is characterized by evolution of the hepatitis C virus (HCV) quasispecies. Little is known about the changes occurring within the HCV genomes when nonresponder patients are retreated with IFN or with IFN plus ribavirin. In the present study we have examined the genetic divergence of HCV quasispecies during unsuccessful retreatment with IFN or IFN plus ribavirin. Fifteen nonresponder patients with HCV-1 (4 patients with HCV-1a and 11 patients with HCV-1b) infection were studied while being retreated for 2 months (phase 1) with IFN-α (6 MU given three times a week), followed by IFN plus ribavirin or IFN alone for an additional 6 months (phase 2). HCV quasispecies diversification in the E2 hypervariable region-1 (HVR1) and in the putative NS5A IFN sensitivity determining region (ISDR) were analyzed for phase 1 and phase 2 by using the heteroduplex tracking assay and clonal frequency analysis techniques. A major finding of this study was the relatively rapid evolution of the HCV quasispecies observed in both treatment groups during the early phase 1 compared to the late phase 2 of treatment. The rate of quasispecies diversification in HVR1 was significantly higher during phase 1 versus phase 2 both in patients who received IFN plus ribavirin (
P
= 0.017) and in patients who received IFN alone (
P
= 0.05). A trend toward higher rates of quasispecies evolution in the ISDR was also observed during phase 1 in both groups, although the results did not reach statistical significance. However, the NS5A quasispecies appeared to be rather homogeneous and stable in most nonresponder patients, suggesting the presence of a single well-fit major variant, resistant to antiviral treatment, in agreement with published data which have identified an IFN sensitivity determinant region within the NS5A. During the entire 8 months of retreatment, there was no difference in the rate of fixation of mutation between patients who received combination therapy and patients who were treated with IFN alone, suggesting that ribavirin had no major effects on the evolution of the HCV quasispecies after the initial 2 months of IFN therapy.
Tyrosine Phosphorylation of A17 during Vaccinia Virus Infection: Involvement of the H1 Phosphatase and the F10 Kinase
Authors: Derrien M. , Punjabi A. , Khanna M. , Grubisha O. , Traktman P.
Published: December 2019

Vaccinia virus encodes two protein kinases (B1 and F10) and a dual-specificity phosphatase (VH1), suggesting that phosphorylation and dephosphorylation of substrates on serine/threonine and tyrosine residues are important in regulating diverse aspects of the viral life cycle. Using a recombinant in which expression of the H1 phosphatase can be regulated experimentally (vindH1), we have previously demonstrated that repression of H1 leads to the maturation of noninfectious virions that contain several hyperphosphorylated substrates (K. Liu et al., J. Virol. 69:7823–7834). In this report, we demonstrate that among these is a 25-kDa protein that is phosphorylated on tyrosine residues in H1-deficient virions and can be dephosphorylated by recombinant H1. We demonstrate that the 25-kDa phosphoprotein represents the product of the A17 gene and that A17 is phosphorylated on serine, threonine, and tyrosine residues during infection. Detection of phosphotyrosine within A17 is abrogated when Tyr203(but not Tyr3, Tyr6, or Tyr7) is mutated to phenylalanine, suggesting strongly that this amino acid is the site of tyrosine phosphorylation. Phosphorylation of A17 fails to occur during nonpermissive infections performed with temperature-sensitive mutants defective in the F10 kinase. Our data suggest that this enzyme, which was initially characterized as a serine/threonine kinase, might in fact have dual specificity. This hypothesis is strengthened by the observation thatEscherichia coliinduced to express F10 contain multiple proteins which are recognized by antiphosphotyrosine antiserum. This study presents the first evidence for phosphotyrosine signaling during vaccinia virus infection and implicates the F10 kinase and the H1 phosphatase as the dual-specificity enzymes that direct this cycle of reversible phosphorylation.
Characterization of the
oriI
and
oriII
Origins of Replication in Phage-Plasmid P4
Authors: Tocchetti Arianna , Galimberti Gloria , Dehò Gianni , Ghisotti Daniela
Published: December 2019

In the
Escherichia coli
phage-plasmid P4, two partially overlapping replicons with bipartite
ori
sites coexist. The essential components of the
oriI
replicon are the α and
cnr
genes and the
ori1
and
crr
sites; the
oriII
replicon is composed of the α gene, with the internal
ori2
site, and the
crr
region. The P4 α protein has primase and helicase activities and specifically binds type I iterons, present in
ori1
and
crr
. Using a complementation test for plasmid replication, we demonstrated that the two replicons depend on both the primase and helicase activities of the α protein. Moreover, neither replicon requires the host DnaA, DnaG, and Rep functions. The bipartite origins of the two replicons share the
crr
site and differ for
ori1
and
ori2
, respectively. By deletion mapping, we defined the minimal
ori1
and
ori2
regions sufficient for replication. The
ori1
site was limited to a 123-bp region, which contains six type I iterons spaced regularly close to the helical periodicity, and a 35-bp AT-rich region. Deletion of one or more type I iterons inactivated
oriI
. Moreover, insertion of 6 or 10 bp within the
ori1
region also abolished replication ability, suggesting that the relative arrangement of the iterons is relevant. The
ori2
site was limited to a 36-bp P4 region that does not contain type I iterons. In vitro, the α protein did not bind
ori2
. Thus, the α protein appears to act differently at the two origins of replication.
Inhibitory Activity of Constitutive Nitric Oxide on the Expression of Alpha/Beta Interferon Genes in Murine Peritoneal Macrophages
Authors: Guillemard Eric , Varano Barbara , Belardelli Filippo , Quero A. M. , Gessani Sandra
Published: December 2019

We investigated the role of the constitutive nitric oxide (NO) in the expression of interferon (IFN) genes in mouse peritoneal macrophages (PM). The treatment of PM withl-arginine-NG-amine (AA), a potent inhibitor of NO-producing enzymes, resulted in a marked accumulation of IFN-α4 mRNA and, to a minor extent, of IFN-β mRNA. In contrast, the expression of IFN-γ mRNA, as well as tumor necrosis factor alpha and interleukin-6 mRNA, was not affected. Furthermore, a remarkable increase in the expression of the IFN regulating factor 1 (IRF-1), but not of IRF-2, mRNA was detected in AA-treated PM. To investigate whether the AA-induced activation of the IFN system correlates with the production and antiviral activity of IFN, the extent of encephalomyocarditis virus (EMCV) replication was monitored in AA-treated PM with respect to control cultures. AA treatment strongly inhibited, in a dose-dependent manner, EMCV yields in PM. Likewise, similar results were obtained by the addition of the NO-scavenger carboxyphenyl-tetramethylimidazoline-oxyl-oxide. In addition, inhibition of NO synthesis byNG-mono-methyl-l-arginine in PM strongly decreased virus replication in coculture of PM and EMCV-infected L929 cells, whereas no antiviral effect was observed in L929 cells alone. Moreover, the AA-mediated antiviral activity was abrogated in the presence of antibody to IFN-α/β, whereas antibody to IFN-γ was completely ineffective. Taken together, these results indicate that low levels of NO, constitutively released by resting PM, negatively regulate the expression and activity of IFN-α/β in PM. We suggest that NO acts as a homeostatic agent in the regulation of IFN pathway expression in macrophages.
Point Mutations in the Avian Sarcoma/Leukosis Virus 3′ Untranslated Region Result in a Packaging Defect
Authors: Aschoff Jonathan M. , Foster Douglas , Coffin John M.
Published: December 2019

The 3′ untranslated region (3′ UTR) between the 3′ end of
env
and the long terminal repeat is well conserved among avian retroviruses and is essential for efficient replication. Deletion of the dr1 element within the 3′ UTR has been reported to have various effects, including reduced levels of unspliced RNA in the cytoplasm, decreased stability of unspliced RNA, decreased particle production, and decreased genomic RNA packaging. To probe the role of specific sequences within dr1 in virus replication, site-directed mutagenesis was utilized to perturb parts of the predicted secondary structure of dr1. Seven of thirteen mutations had no significant effect; the others resulted in an approximately 10- to 20-fold reduction in replication. These mutants were further characterized and found to impair cytoplasmic accumulation of unspliced RNA only slightly. Furthermore, no decreases were observed in the stability of the unspliced RNA or in the production of virus particles. Genomic RNA packaging, however, was reduced by about 10-fold. Similar amounts of particles were produced by cells containing the mutant and wild-type DNA, and all particles contained similar levels of reverse transcriptase activity. The results suggest that the region of the dr1 disrupted by the mutations plays a role in genomic RNA packaging, although that packaging may not be the only role for dr1.
An Inducible Human Immunodeficiency Virus Type 1 (HIV-1) Vector Which Effectively Suppresses HIV-1 Replication
Authors: An Dong Sung , Morizono Kouki , Li Qi-Xiang , Mao Si Hua , Lu Stephanie , Chen Irvin S. Y.
Published: December 2019

Recently, gene therapy vectors based upon the human immunodeficiency virus type 1 (HIV-1) genome have been developed. Here, we create an HIV-1 vector which is defective for all HIV-1 genes, but which maintains
cis
-acting elements required for efficient packaging, infection, and expression. In T cells transduced by this vector, vector expression is low but efficiently induced following HIV-1 infection. Remarkably, although the HIV-1 vector does not contain specific anti-HIV-1 therapeutic genes, the presence of the vector alone is sufficient to inhibit the spread of HIV-1 infection. The mechanism of inhibition is likely to be at the level of competition for limiting substrates required for either efficient packaging or reverse transcription, thereby selecting against propagation of wild-type HIV-1. These results provide proof of a concept for potential application of a novel HIV-1 vector in HIV-1 disease.
Evolution and Horizontal Transfer of dUTPase-Encoding Genes in Viruses and Their Hosts
Authors: Baldo Angela M. , McClure Marcella A.
Published: December 2019

dUTPase is a ubiquitous and essential enzyme responsible for regulating cellular levels of dUTP. The
dut
gene exists as single, tandemly duplicated, and tandemly triplicated copies. Crystallized single-copy dUTPases have been shown to assemble as homotrimers. dUTPase is encoded as an auxiliary gene in a number of virus genomes. The origin of viral
dut
genes has remained unresolved since their initial discovery. A comprehensive analysis of dUTPase amino acid sequence relationships was performed to explore the evolutionary dynamics of
dut
in viruses and their hosts. Our data set, comprised of 24 host and 51 viral sequences, includes representative sequences from available eukaryotes, archaea, eubacteria cells, and viruses, including herpesviruses. These amino acid sequences were aligned by using a hidden Markov model approach developed to align divergent data. Known secondary structures from single-copy crystals were mapped onto the aligned duplicate and triplicate sequences. We show how duplicated dUTPases might fold into a monomer, and we hypothesize that triplicated dUTPases also assemble as monomers. Phylogenetic analysis revealed at least five viral dUTPase sequence lineages in well-supported monophyletic clusters with eukaryotic, eubacterial, and archaeal hosts. We have identified all five as strong examples of horizontal transfer as well as additional potential transfer of
dut
genes among eubacteria, between eubacteria and viruses, and between retroviruses. The evidence for horizontal transfers is particularly interesting since eukaryotic
dut
genes have introns, while DNA virus
dut
genes do not. This implies that an intermediary retroid agent facilitated the horizontal transfer process between host mRNA and DNA viruses.
Three-Dimensional Structure of Herpes Simplex Virus Type 1 Glycoprotein D at 2.4-Nanometer Resolution
Authors: Pilling Andrew , Rosenberg Mark F. , Willis Sharon H. , Jäger Joachim , Cohen Gary H. , Eisenberg Roselyn J. , Meredith David M. , Holzenburg Andreas
Published: December 2019

Herpes simplex virus type 1 glycoprotein D (gD) is essential for virus infectivity and is responsible for binding to cellular membrane proteins and subsequently promoting fusion between the virus envelope and the cell. No structural data are available for gD or for any other herpesvirus envelope protein. Here we present a three-dimensional model for the baculovirus-expressed truncated protein gD1(306t) based on electron microscopic data. We demonstrate that gD1(306t) appears as a homotetramer containing a pronounced pocket in the center of the molecule. Monoclonal antibody binding demonstrates that the molecule is oriented such that the pocket protrudes away from the virus envelope.
Middle T Antigen Activation of Signal Transduction Pathways Does Not Overcome p53-Mediated Growth Arrest
Authors: Doherty Joanne , Freund Robert
Published: December 2019

Polyomavirus middle T antigen does not overcome p53-mediated G
1
arrest in mouse embryo fibroblasts. Middle T antigen still associates with the signaling molecules phosphatidylinositol 3-kinase and SHC and activates the transcriptional activity of c-Myc and AP1 in p53-arrested cells. Examination of cell cycle regulatory proteins indicated that p53 does not interfere with these mitogenic signals but acts later in the G
1
phase of the cell cycle.
Creating and Maintaining the Gastrointestinal Ecosystem: What We Know and Need To Know from Gnotobiology
Authors: Falk Per G. , Hooper Lora V. , Midtvedt Tore , Gordon Jeffrey I.
Published: December 2019

Studying the cross talk between nonpathogenic organisms and their mammalian hosts represents an experimental challenge because these interactions are typically subtle and the microbial societies that associate with mammalian hosts are very complex and dynamic. A large, functionally stable, climax community of microbes is maintained in the murine and human gastrointestinal tracts. This open ecosystem exhibits not only regional differences in the composition of its microbiota but also regional differences in the differentiation programs of its epithelial cells and in the spatial distribution of its component immune cells. A key experimental strategy for determining whether “nonpathogenic” microorganisms actively create their own regional habitats in this ecosystem is to define cellular function in germ-free animals and then evaluate the effects of adding single or several microbial species. This review focuses on how gnotobiotics—the study of germ-free animals—has been and needs to be used to examine how the gastrointestinal ecosystem is created and maintained. Areas discussed include the generation of simplified ecosystems by using genetically manipulatable microbes and hosts to determine whether components of the microbiota actively regulate epithelial differentiation to create niches for themselves and for other organisms; the ways in which gnotobiology can help reveal collaborative interactions among the microbiota, epithelium, and mucosal immune system; and the ways in which gnotobiology is and will be useful for identifying host and microbial factors that define the continuum between nonpathogenic and pathogenic. A series of tests of microbial contributions to several pathologic states, using germ-free and ex-germ-free mice, are proposed.
Retroviral DNA Integration
Authors: Hindmarsh Patrick , Leis Jonathan
Published: December 2019

DNA integration is a unique enzymatic process shared by all retroviruses and retrotransposons. During integration, double-stranded linear viral DNA is inserted into the host genome in a process catalyzed by the virus-encoded integrase (IN). The mechanism involves a series of nucleophillic attacks, the first of which removes the terminal 2 bases from the 3′ ends of the long terminal repeats and of the second which inserts the viral DNA into the host genome. IN specifically recognizes the DNA sequences at the termini of the viral DNA, juxtaposing both ends in an enzyme complex that inserts the viral DNA into a single site in a concerted manner. Small duplications of the host DNA, characteristic of the viral IN, are found at the sites of insertion. At least two host proteins, HMG-I(Y) and BAF, have been shown to increase the efficiency of the integration reaction.
Intracranial pellet embolization: an endovascular endeavor
Authors: Hassan Ameer E , Rabah Rani Ramsey , Tekle Wondwossen
Published: December 2019

A 44-year-old man was referred to the neurointerventionalist 6 hours after sustaining a shotgun wound to the left chest, shoulder, and neck from 4 feet away. Physical examination of the chest showed a 5 cm × 5 cm gunshot entry wound on the anterior-superior aspect of the chest involving the supraclavicular and infraclavicular region, with multiple gunshot pellet entry sites riddled in the surrounding vicinity. The patient was taken for a CT scan of the brain without contrast and CT angiography, which showed no sign of stroke or intracranial hemorrhage but revealed a single 'buckshot' pellet embolizing the basilar artery tip, occluding the origin of the left posterior cerebral artery. Using A Direct Aspiration First Pass Technique (ADAPT), the neurointerventinalist was able to endovascularly remove the embolized pellet and the patient was discharged 8 days later with no focal neurological deficit.
History, treatment and analysis of a rare form of Exeter stem fracture
Authors: Moloney Darren Patrick , Hurley Robert J , Harty James , Guerin Shane
Published: December 2019

The Exeter stem by Stryker has become one of the most successful and widely used stems in modern cemented hip arthroplasty. We present a case of a rare stem fracture which was treated by ‘cement-in-cement’ revision arthroplasty technique. The patient, an 87-year-old man, presented with left hip pain and an inability to weight bear following a cracking sensation when he was standing to dress himself. The patient denied history of fall or trauma. On examination he was noted to have a shortened externally rotated left lower limb without neurovascular compromise. On pelvic radiograph he was noted to have an incomplete stem fracture of his left-sided total hip replacement. He was treated with a cement-in-cement revision. Postoperatively the stem was sent for analysis in the London Implant Retrieval Centre. This is an example of a rare form of stem fatigue failure treated with a well-described technique in revision arthroplasty.
Chylothorax as a complication of extensive spontaneous left arm DVT
Authors: Gohar Ahmed , Jamous Fady , Meyer Natasha
Published: December 2019

We present a case of right sided chylothorax in the setting of cirrhosis believed to be secondary to extensive venous thromboembolism of the left upper extremity and exacerbated by chylous ascites. Our patient responded to conservative management with anticoagulation and a repeat thoracentesis revealed transformation of the fluid back to straw coloured transudate. We also include a brief discussion of the diagnosis and management of chylothorax.
Postoperative cardiogenic shock secondary to Takotsubo’s syndrome
Authors: Dessain Tessa , Stewart Rachel , Patil Shashank
Published: December 2019

Takotsubo’s syndrome is a rare acute reversible heart failure, where the pathophysiology is not fully understood. It is being increasingly diagnosed in varied clinical contexts, which can result in atypical presentations in the context of surgical or anaesthetic stress. We discuss the case of a 22-year-old woman who developed cardiogenic shock and impaired left ventricular function after an elective gynaecological procedure. She had a rapid recovery and a follow-up cardiac MRI confirmed Takotsubo’s syndrome.
Timing of delivery in women with pre-pregnancy diabetes mellitus: a population-based study
Authors: Brown Meghan , Melamed Nir , Murray-Davis Beth , Hassan Haroon , Mawjee Karizma , Barrett Jon , McDonald Sarah D , Ray Joel G , Geary Michael , Berger Howard
Published: December 2019

Objectives

Controversy exists about the timing of delivery of women with pre-pregnancy type 1 and 2 diabetes mellitus (PDM). This study aims to compare maternal and neonatal outcomes after induction of labor (IOL) at 38 weeks’ gestation versus expectant management from 39 weeks onward.

Research design and methods

This was a retrospective population-based cohort study using data from the Better Outcomes Registry and Network in Ontario Canada. Included were all women with PDM, who had a singleton hospital birth at ≥380/7weeks’ gestation from 2012 to 2017. Maternal and perinatal outcomes were compared between 937 pregnancies that underwent IOL at 380/7–386/7weeks (‘38-IOL group’) versus 1276 pregnancies expectantly managed resulting in a birth at ≥390/7weeks (‘39-Exp group’). The primary outcome was all-cause cesarean delivery. Multivariable modified Poisson regression was performed to generate adjusted relative risks (aRR) and 95% CIs, adjusted for parity, maternal age, pre-pregnancy body mass index and PDM type. Other outcomes included instrumental delivery, neonatal intensive care unit (NICU) admission, and newborn metabolic disturbances.

Results

Cesarean delivery occurred in 269 women (28.7%) in the 38-IOL group versus 333 women (26.1%) in the 39-Exp group—aRR 1.07 (95% CI 0.94 to 1.22). The respective rates of instrumental delivery were 11.2% and 10.2% (aRR 1.25, 95% CI 0.98 to 1.61). NICU admission was more common in the 38-IOL group (27.6%) than in the 39-Exp group (16.8%) (aRR 1.61, 95% CI 1.36 to 1.90), as were jaundice requiring phototherapy (12.4% vs 6.2%) (aRR 1.93, 95% CI 1.46 to 2.57) and newborn hypoglycemia (27.3% vs 14.7%) (aRR 1.74, 95% CI 1.46 to 2.07).

Conclusion

In pregnant women with PDM, IOL at 380/7–386/7weeks was not associated with a higher risk of cesarean delivery, compared with expectant management, but was associated with a higher risk of certain adverse neonatal outcomes.
Advancing child nutrition science in the scaling up nutrition era: a systematic scoping review of stunting research in Guatemala
Authors: Cordon Ana , Asturias Gabriela , De Vries Thomas , Rohloff Peter
Published: December 2019

Introduction

Ever since the 1960s, Guatemala has been a principle site for global academic research on child growth and nutrition. Nevertheless, Guatemala still has one of the highest rates of child stunting in the world. Since 2012, Guatemala has had a comprehensive national policy on stunting, calling for a renewed investment in innovative, multilevel nutrition interventions and implementation science. Our objective was to perform a systematic search and scoping review of the literature on stunting in Guatemala to identify gaps in research and opportunities for responding to this unique policy opportunity.

Methods

We conducted a systematic search and scoping review on stunting in Guatemala, searching the PubMed, Web of Science and PsycINFO databases. Eligible articles were of any design or format, published in English and Spanish from 2000 to 2018. Articles were thematically grouped by those published before (2000–2011) and after (2012–2018) the new national policy initiatives.

Results

We identified a total of 1934 articles through database searches. After full-text review, 104 were included in the synthesis. The volume of published articles on stunting increased from a mean of 3.2 to 9.4 articles/year before and after 2012. There was a shift toward articles generating new data on priority populations, including rural indigenous Maya populations (34% vs 61%, χ2 test, p=0.01). However, the proportion of studies conducting implementation evaluations or testing new interventions was low and did not change significantly (34% vs 18%, χ2 test, p=0.07). Among 17 identified intervention studies, only 4 tested multilevel interventions, and there were no published interventions incorporating nutrition-sensitive interventions.

Conclusions

A systematic search and scoping review of the literature on child stunting in Guatemala identified critical opportunities for new research in multilevel interventions, nutrition-sensitive interventions and implementation science.
Hyaluronic Acid Injections as Nonsurgical Alternative in case of Delayed Diagnosis of Malar Arch Fracture: Case Report and Literature Review
Authors: Rauso Raffaele , Lo Giudice Giorgio , Zerbinati Nicola , Tartaro Gianpaolo
Published: December 2019

Background. In this article, we describe a nonsurgical approach based on hyaluronic acid filler injection to restore the facial features of a delayed diagnosis of malar fracture. We analyze the differences between surgical and nonsurgical solution: in case of early detection, the surgical approach is the gold standard of treatment. However, in cases of delayed facial fracture diagnosis without functional impairment, nonsurgical procedures could be considered an alternative tool as we show in the present case report.Aims.The aim of this study is to underline the importance of a complete aesthetic restoration in patients treated for noncosmetic purposes.Patients/Methods. We present a case of a 26-year-old male patient with a delayed diagnosis of malar fracture without functional impairment that was treated with hyaluronic acid (HA) filler injections.Results. The patient was followed up for 1 year showing stable results for the first 8 months; at the 12-month follow-up, a touch-up was suggested due to partial resorption of the filler.Conclusion. This is the first case describing a facial fracture treated with HA injections for only recontouring purposes. We assess that nonsurgical cosmetic procedures could be considered a “new” tool in the process of facial rehabilitation but only when functional problems are not associated with facial trauma.
Discretization of Optimal Control Problems Governed by p-Laplacian Elliptic Equations
Authors: Luan Shu
Published: December 2019

In this paper, a state-constrained optimal control problem governed by p-Laplacian elliptic equations is studied. The feasible control set or the cost functional may be nonconvex, and the purpose is to obtain the convergence of a solution of the discretized control problem to an optimal control of the relaxed continuous problem.
Remifentanil Protects against Lipopolysaccharide-Induced Inflammation through PARP-1/NF-κB Signaling Pathway
Authors: Zhang Jian-ning , Ma Yang , Wei Xi-yan , Liu Ke-yin , Wang Hao , Han Hui , Cui Yi , Zhang Ming-xiang , Qin Wei-dong
Published: December 2019

Sepsis is a leading cause of death in patients with severe infection worldwide. Remifentanil is an ultra-short-acting, potent opioid analgesic. In the study, we aimed to investigate the role and underlying mechanism of remifentanil in lipopolysaccharide- (LPS-) induced inflammation in human aortic endothelial cells (HAECs). HAECs were pretreated with phosphate-buffered saline (PBS) or remifentanil (2.5 μM) for 30 min, then stimulated by LPS (10 μg/ml) for another 24 h. Poly(ADP-ribose) polymerase 1 (PARP-1) was inhibited by small interfering RNA (siRNA). Superoxide anion production and DNA damage were analyzed by dihydroethidium (DHE) staining and comet assay. The inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM-1), PARP-1, poly(ADP-ribose) (PAR), and nuclear factor-kappa B p65 (NF-κB p65) expressions were analyzed by RT-PCR or western blotting analysis. NF-κB p65 nuclear translocation was assessed by immunofluorescence. Compared with the control group, pretreatment with remifentanil significantly reduced superoxide anion production and DNA damage, with downregulation of iNOS, ICAM-1, and PARP-1 expressions as well as PAR expression. Moreover, pretreatment with PARP-1 siRNA or remifentanil inhibited LPS-induced NF-κB p65 expression and nuclear translocation. Remifentanil reduced LPS-induced inflammatory response through PARP-1/NF-κB signaling pathway. Remifentanil might be an optimal choice of analgesia in septic patients.
TGF-β3 Induces Autophagic Activity by Increasing ROS Generation in a NOX4-Dependent Pathway
Authors: Zhang Yun , Tang Hong-Mei , Liu Chun-Feng , Yuan Xie-Fang , Wang Xiao-Yun , Ma Ning , Xu Guo-Feng , Wang Song-Ping , Deng Jun , Wang Xing
Published: December 2019

Higher concentrations of reactive oxygen species (ROS) have been associated with epithelial cell damage, cell shedding, and airway hyperresponsiveness. Previous studies have indicated that transforming growth factor-beta (TGF-β) mediates ROS production and NADPH oxidase (NOX) activity. In our previous study, we also observed that TGF-β3 increases mucus secretion in airway epithelial cells in an autophagy-dependent fashion. Although it is well known that the relationship between ROS and autophagy is cell context-dependent, the exact mechanism of action remains unclear. The following study examined whether ROS act as upstream of autophagy activation in response to TGF-β3 induction. Using an allergic inflammation mouse model induced by house dust mite (HDM), we observed elevated lung amounts of TGF-β3 accompanied by increased ROS levels. And we found that ROS levels were elevated and NOX4 expression was increased in TGF-β3-induced epithelial cells, while the lack of NOX4 in the epithelial cells could reduce ROS generation and autophagy-dependent MUC5AC expression treated with TGF-β3. Furthermore, our studies demonstrated that the Smad2/3 pathway was involved in TGF-β3-induced ROS generation by promoting NOX4 expression. The inhibition of ROS generation by N-Acetyl-L-cysteine (NAC) resulted in a decrease in mucus expression and autophagy activity in vivo as well as in vitro. Finally, TGF-β3-neutralizing antibody significantly reduced the ROS generation, mucus expression, and autophagy activity and also decreased the phosphorylation of Smad2 and Smad3. Taken together, the obtained results revealed that persistent TGF-β3 activation increased ROS levels in a NOX4-dependent pathway and subsequently induced autophagy as well as MUC5AC expression in the epithelial cells.
Insulin Glargine U100 Utilization in Patients with Type 2 Diabetes in an Italian Real-World Setting: A Retrospective Study
Authors: Degli Esposti Luca , Perrone Valentina , Saragoni Stefania , Blini Valerio , Buda Stefano , D’avella Rosella , Gasperini Gina , Lena Fabio , Fanelli Francesca , Gazzi Luca , Giorgino Francesco
Published: December 2019

Background. This study is aimed at estimating the proportion of type 2 diabetes mellitus (T2DM) patients treated with basal insulin (insulin glargine U100) and at evaluating daily insulin dose, treatment pattern, and adherence to treatment of these patients. Methods. Data from administrative and laboratory databases of 3 Italian Local Health Units were retrospectively collected and analyzed. All patients with a diagnosis of T2DM between 01/01/2012 and 31/12/2012 were considered, and those with at least a prescription of insulin glargine between 01/01/2013 and 31/12/2014 were included and followed up for one year. For each patient, we evaluated HbA1c levels both at baseline and during the follow-up period and the daily average dose of insulin. Medication adherence was defined by using medication possession ratio (MPR) and reported as proportion of patients with MPR≥80%. Results. 7,422 T2DM patients were available for the study. According to the antidiabetic medication prescribed, patients were categorized into four groups: insulin glargine only, insulin glargine plus oral glucose-lowering drugs, insulin glargine plus rapid-acting insulin, and insulin glargine plus DPP-4 inhibitors. Median daily dose of insulin among insulin glargine only patients was higher than in other groups (35 IU vs. 20 IU, p<0.05), and a higher percentage of them achieved a target HbA1c value of less than 7.0% (53.8% vs. 30%, p<0.001). Adherence to insulin treatment was lowest (41%) in the insulin glargine only group compared to other groups (ranging from 58.4% to 64.4%), p<0.001. Conclusions. A large proportion of T2DM patients treated with insulin fail in achieving the glycemic target of HbA1c level<7%, irrespective of treatment regimen; however, basal insulin only is associated with lower therapeutic unsuccess. Adherence to antidiabetes medications is also suboptimal in these patients and should be addressed to improve long-term outcomes of reducing and preventing microvascular and macrovascular complications.
A Rare Case of Sclerosing Stromal Tumor of the Ovary Presenting in Pregnancy: A Diagnostic Dilemma on Presentation
Authors: Nguyen Minh , Soumit Namarig , Waheed Abdul , Sees Jack , Azhar Erum
Published: December 2019

Sclerosing stromal tumor (SST) is a rare benign neoplasm of the ovary. There are only a few cases of sclerosing stromal tumor of the ovary during pregnancy that have been reported in the literature. The presenting symptoms are nonspecific, including pelvic pain or menstrual irregularities. We describe a case of a young 22-year-old pregnant woman who presented with pelvic pain in the second trimester. On imaging she was found to have a 12 cm left adnexal mass with solid features on MRI. The patient underwent exploratory laparotomy and removal of the mass that was attached to the left ovary via a stalk with preservation of the left ovary. The frozen section diagnosis was “sex cord stromal tumor, favor benign”. The final pathology confirmed the diagnosis of the sclerosing stromal tumor of the ovary where characteristic features of SST including a heterogenous, pseudolobular growth pattern with hypercellular and hypocellular areas were identified along with prominent luteinized stromal cells attributed to pregnancy. In this case report and review of literature, we emphasize consideration of this rare ovarian tumor in the differential diagnosis for a young pregnant woman who presents with pelvic pain.
Intestinal Microbiome Changes in Fecal Microbiota Transplant (FMT) vs. FMT Enriched with Lactobacillus in the Treatment of Recurrent Clostridioides difficile Infection
Authors: Garza-González Elvira , Mendoza-Olazarán Soraya , Morfin-Otero Rayo , Ramírez-Fontes Andrea , Rodríguez-Zulueta Patricia , Flores-Treviño Samantha , Bocanegra-Ibarias Paola , Maldonado-Garza Héctor , Camacho-Ortiz Adrián
Published: December 2019

Aim. In this study, we conducted a comparative study to explore the differences in therapeutic efficacy and intestinal microbiome of fecal microbiota transplant (FMT) vs. FMT in addition with Lactobacillus (FMT-L) for treatment of recurrent Clostridioides difficile infection (R-CDI). Methods. We designed a double-blinded randomized comparative two-arm pilot multicenter study to assess the efficacy and impact in the intestinal microbiome of standard capsules of FMT vs. FMT-L enriched with 3 species of Lactobacillus for patients with R-CDI. A 90-day follow-up of 21 patients was performed, starting at the beginning of the study. From the selected patients, fecal samples were obtained at days 0, 3, 7, and 28 after treatment. Fecal samples and FMT were analyzed by 16S rRNA sequencing. Results. We included 21 patients (13 in the FMT group and 8 in the FMT-L group). Overall, both groups had a reduction in bowel movements per day, from 8.6 to 3.2 in the first 48 h (62.7% reduction, p=0.001). No severe adverse reactions or recurrences were recorded. Firmicutes were the most abundant phylum in donors. A low relative abundance of Proteobacteria was detected and mostly found in patients even at higher proportions than the donor. The donor’s pool also had relatively few Bacteroidetes, and some patients showed a higher abundance of this phylum. Based on the ANOSIM R values, there is a significant difference between the microbial communities of basal samples and samples collected on day 7 (p=0.045) and at day 28 (0.041). Conclusion. Fecal microbiota transplant by capsules was clinically and genomically similar between traditional FMT and enriched FMT with Lactobacillus spp. Restoration of bacterial diversity and resolution of dysbiosis at days 7 and 28 were observed. Patients with a first episode of recurrence treated with FMT had an excellent response without severe adverse events; FMT should be considered as an early treatment during R-CDI.
Compact Implementations of HIGHT Block Cipher on IoT Platforms
Authors: Kim Bohun , Cho Junghoon , Choi Byungjun , Park Jongsun , Seo Hwajeong
Published: December 2019

Recent lightweight block cipher competition (FELICS Triathlon) evaluates efficient implementations of block ciphers for Internet of things (IoT) environment. In the competition, the implementation of HIGHT block cipher achieved the most efficient lightweight block cipher, in terms of code size (ROM), memory (RAM), and execution time. In this paper, we further investigate lightweight features of HIGHT block cipher and present the optimized implementations of both software and hardware for low-end IoT platforms, including resource-constrained devices (8-bit AVR and 32-bit ARM Cortex-M3) and application-specific integrated circuit (ASIC). By using proposed optimization methods, the implemented HIGHT block cipher shows better performance compared to previous state-of-the-art implementations.
A Tanzanian Boy with Molecularly Confirmed X-Linked Adrenoleukodystrophy
Authors: Dekker M. C. J. , Sadiq A. M. , Mc Larty R. , Mbwasi R. M. , Willemsen M. A. A. P. , Waterham H. R. , Hamel B. C.
Published: December 2019

Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder with classical features, which can be also recognised in a low resource setting. It had been described in various populations across the globe, but very few cases have been reported from Africa. In a boy with features of a progressive central nervous system condition and adrenal failure, ABCD1 gene screening was performed based on a clinical history and basic radiological features which were compatible with ALD. A common ABCD1 mutation was identified in this patient, which is the first report of genetically confirmed ALD in Sub-Saharan Africa. ALD is likely under recognised in those areas where there is no neurologist. This genetic confirmation widens geographical distribution of ABCD1-associated disease, and illustrates recognisability of this disorder, even when encountered in a low-resource environment.
No Severe Adverse Effects from Intravitreally Injected Putative Adipose Tissue-Derived Stem Cells
Authors: Faber Carsten , Heegaard Steffen , Kiilgaard Jens Folke
Published: December 2019

This study reports findings from a 56-year-old patient, who had received bilateral intravitreal injection of putative adipose tissue-derived stem cells at a private clinic in India with the promise of treatment of NAION. During an observation period of 8, respectively, 18 months, the intravitreally injected cells remained silent in the vitreous bodies without either therapeutic effects or complications. The cells cleared with vitrectomy without evidence of integration in the optic nerve or retina. Contrary to recent reports on patients receiving intravitreal injections of similar putative stem cells with the aim of treating AMD, our patient suffered no devastating ocular consequences. Summary. Contrary to recent reports, this case demonstrated no devastating consequences of intravitreal injection of adipose tissue-derived stem cells during an observation period of up to 18 months. After vitrectomy, the cells cleared without evidence of either harm or integration.
O movimento literário cyberpunk: a estética de uma sociedade em declínio
Authors: Aranha Glaucio
Published: December 2019

Este ensaio aborda o movimento literário cyberpunk. Propõe uma reflexão sobre o modo como os autores deste subgênero de ficção científica trataram esteticamente as expectativas de transformações sociais em face a emergência das novas tecnologias de comunicação na década de 1980. Busca-se identificar como o movimento sentiu e representou as questões e tensões sociais em relação a um futuro cada vez mais marcado por um imperativo tecnológico e pelo capitalismo contemporâneo. Parte-se da contextualização do objeto, para em seguida analisar as transformações de paradigmas ocorridas ao longo da existência do movimento literário até sua saturação e seu desdobramento na chamada literatura pós-cyberpunk.
As crônicas de Júlio Gonçalves na revista illustração goana
Authors: Oliveira Filho José Antonio Pires de
Published: December 2019

O presente artigo faz uma breve apresentação sobre as crônicas produzidas por Júlio Gonçalves no periódico goês Ilustração Goana no século XIX. Conhecido como o primeiro contista em língua portuguesa em Goa, o autor também contribuiu muito com o periodismo literário local, pois criou e dirigiu esta que foi a revista literária com maior duração, assim como escreveu nela a mais importante parte de sua obra. As crônicas, gênero ligeiro que se estabelece entre o conteúdo literário e a velocidade jornalística têm também importância ainda pouco explorada na produção desse autor.
Women writing and writings on women in the goan magazine o acadêmico (1940 – 1943)
Authors: Madeira Viviane Souza
Published: December 2019

This article discusses some of the texts written about women by men as well as those written by women in the Goan magazine O Académico (1940-1943). Even though O Académico is not particularly aimed at women’s readership, but at a broader audience – the “Goan youth” – it contains articles that deal with the question of women in the spheres of science, politics and literature. As one of the magazine’s objectives was to “emancipate Goan youth intellectually”, we understand that young women’s education was also within the their scope, placing the question of gender as central. The Goan intelligentsia that made up the editorial board of the publication revealed their desire for modernization by showing their preoccupation with forward-looking ideas and by providing the space for women to publish their texts.
Em torno do fim da linha: goa tardo-colonial no ciclo de contos monção de Vimala Devi (1963/2003)
Authors: Castro Paul Melo e
Published: December 2019

Neste artigo, analisamos Monção (1963) da escritora goesa Vimala Devi como um ciclo de contos, ou seja, um género que difere tanto do romance tradicional quanto da coletânea não integrada de curtas narrativas, alvitrando que esta afiliação genérica torna possível uma peculiar representação de Goa tardo-colonial. Apoiando-nos em várias teorizações das características desse género, esmiuçamos as interligações e rupturas presentes neste ciclo, concluindo que é essa oscilação entre forças centrípetas e centrífugas que perfazem o retrato de uma sociedade unida por suas divisões.
Política e literatura na goa oitocentista: em torno da construção de um universo de escritores peristas
Authors: Oliveira Luís Cabral de
Published: December 2019

O presente trabalho pretende realçar a originalidade e importância do contributo goês para a política ultramarina portuguesa do século XIX enfatizando o papel de Bernardo Peres da Silva e do perismo (uma forma de organização constitucional criada na sequência da introdução do liberalismo no Estado da Índia), bem como de uma série de autores pertencentes às elites naturais católicas cujos escritos mantiveram e robusteceram o legado de Peres.
LİDERLİĞİN KARANLIK YÜZÜ VE ÇALIŞANLAR ÜZERİNDEKİ OLUMSUZ ETKİLERİ
Authors: HALİS Muhsin , TÜLEMEZ Soner
Published: December 2019

Bu çalışmanın amacı,
iş yerinde liderliğin karanlık yüzünü oluşturan olumsuz lider davranışlarının,
çalışanlar üzerindeki olumsuz psikolojik ve fizyolojik etkilerini açığa
çıkarmak ve bu etkilerin çalışanların demografik özellikleri bakımından
farklılaşma durumunu incelemektir. Bu bağlamda, Kocaeli ve İstanbul’da çeşitli
sektörlerde faaliyet gösteren 224 çalışana, bağlı bulundukları yöneticilerin
sergilediği olumsuz davranışları ve yöneticilerinin olumsuz davranışlarından
hareketle çalışanlar üzerindeki psikolojik ve fizyolojik etkilerini ölçmek
amaçlanmıştır. Araştırma sonucunda; olumsuz lider davranışlarının çalışanların
üzerinde çeşitli olumsuz psikolojik ve fizyolojik etkileri olduğu tespit
edilmiştir. Çalışanların demografik özellikleri akımından olumsuz lider
davranışları algılarında istatistikî olarak anlamlı bir farklılık olup olmadığı
incelenmiştir. Kadın çalışanların erkek çalışanlardan daha fazla olumsuz lider
davranışlarına maruz kaldığı, bu durumdan hem psikolojik hem de fizyolojik
olarak daha fazla etkilendikleri tespit edilmiştir.