bluuebunny/crossref_metadata_2025 huggingface dataset:
Colloid or crystalloid solution on maternal and neonatal hemodynamics for cesarean section: A meta‐analysis of randomized controlled trials
Authors: Li Le , Zhang Yang , Tan Ying , Xu Shiyuan
Published: February 2013

Aim

To compare the effect of colloid and crystalloid on maternal and neonatal hemodynamics in cesarean section.

Material and Methods

We searched MEDLINE (PubMed, 1966–2011), EMBASE (1974–2011), http://www.clinicaltrials.gov, the Cochrane Controlled Clinical Trials Register Database, Biosis Preview, and the Chinese Biomedical Database (1980–2011). Randomized controlled trials involving healthy term patients undergoing scheduled cesarean delivery that compared the effect of colloid and crystalloid on hypotension, need for vasopressors, cardiac output, neonatal outcomes, and other adverse effects were analyzed.

Results

Ten trials of 853 patients were eligible for analysis. When colloid was used, significantly fewer hypotensive events occurred (odds ratio [OR] 3.21, 95% CI 2.15–4.53, number needed to treat = 4), less demand for vasopressors (standard mean difference [SMD] 0.77, 95% CI 0.34–1.21) and improved cardiac output (SMD −1.08, 95% CI −2.00 – −0.17). In subgroup analysis, the use of colloid reduced hypotensive events and adverse effects in Asian patients.

Conclusion

Colloid hydration should be considered first, especially in Asian patients, focusing on dosage and type of fluids. Preventive or therapeutic vasopressors may be required in a significant proportion of patients.
Mental illness training on the Internet for nurse aides: a replication study
Authors: Irvine A. B. , Billow M. B. , McMahon E. , Eberhage M. G. , Seeley J. R. , Bourgeois M.
Published: February 2013

Accessible summary

Research shows that Internet training for direct care workers in long‐term care facilities is effective, but little is known about how it works in a non‐research setting, and if an available training programme would continue to be used.

Three facilities trained all their direct care workers in a replication study with the same training programme.

Trainees showed very positive effects after the training, showing improved self‐confidence and knowledge about mental illness. Users rated the programme highly, and they indicated that the training would improve the quality of their resident care. Supervisors praised the training, and they said care workers were using recommended training behaviours. Although available to all staff, however, nursing and other staff made little use of the training in subsequent months.

These results suggest that Internet training is feasible, and it is perceived to be beneficial for resident care by trainees. Administrators, however, when they develop plans for staff training on the Internet, need to plan for continued utilization and dissemination of best practices to other staff.

Internet training courses for nurse aides (NAs) in long‐term care facilities (LTCs) have been shown to be effective. Little is known, however, about Internet training effects on NAs in a non‐research context, or about continued utilization of an available training programme. In this research, a replication study was conducted with the Internet training programme Caring Skills: Working with Mental Illness. Three LTCs provided the training to all NAs, each within a 1‐month interval scheduled during consecutive months. Supervisors were interviewed subsequently about their experiences organizing and supervising the training. Participants in all three LTCs showed positive pre–post‐tests effects with large effect sizes on situational knowledge and self‐efficacy, and knowledge about mental illness. Users rated the programme highly, and they indicated that it would improve quality of their resident care. Supervisors praised the training, and they said NAs were using recommended training behaviours. Although available to all staff, nursing and other staff made little use of the training in subsequent months. Training for NAs on the Internet thus appears feasible, and it is perceived to be beneficial for resident care. Plans for continued utilization and dissemination of best practices to other staff, however, should be integrated when planning for staff training on the Internet.
Recovering from childhood sexual abuse: a theoretical framework for practice and research
Authors: Chouliara Z. , Karatzias T. , Gullone A.
Published: February 2013

Accessible summary

Adopting a model of personally meaningful recovery places demands on the therapeutic relationship, on clinical governance and supervision of clinicians.

The recovery journey from childhood sexual abuse (CSA) starts at the point of disclosure.

Findings support the use of shame‐based and compassion‐focused interventions with CSA survivors.

Research on survivors' experiences of recovering from childhood sexual abuse (CSA) has been limited and focused on those with severe mental health difficulties. This study elicited experiences of recovery from CSA in male and female survivors who have/have not utilized mental health services. The tangible end‐point was to propose a theoretical model of personally meaningful recovery. This is a qualitative study, which utilized semi‐structured individual interviews following the critical incident technique. Transcripts were analysed using Interpretative Phenomenological Analysis to identify recurrent themes. A total 22 adult survivors of CSA. Main themes identified were: The Affected Self, Factors Hindering Recovery, Factors Enhancing Recovery, The Hurdles of Recovery and the Recovering Self. The affected self included: lack of boundary awareness and self‐blame, over self‐reliance, over‐vigilance and guilt, shame, aloneness and social stigma. The recovering self was characterized by increasing confidence, assertiveness, ability to self‐care and self‐acceptance, and by embracing vulnerability. These findings have potentially major implications for clinical practice, service provision, policy development and professional training in this field. The importance of disclosure in the healing process seemed paramount and can have major implications for current service protocols.
Hepatitis B virus in the Maghreb Region: from epidemiology to prospective research
Authors: Ezzikouri Sayeh , Pineau Pascal , Benjelloun Soumaya
Published: February 2013

Hepatitis B virus (HBV) represents an important health problem in the Maghreb countries, Algeria, Libya, Mauritania, Morocco and Tunisia, but no detailed synthesis of its epidemiology is available. In this review, we systematically searched for data about HBV in the Maghreb in peer‐reviewed databases and included in our analysis works written in English and French, as well as institutional reports and regional conference meeting abstracts. We estimated national and regional prevalence of chronic HBV infection. In addition, we discuss molecular features of the viral strains circulating in the region.

Data analysis suggests that in the Maghreb region HBs antigen carriage concerns 1.8–4.9% of the population for an estimated number of 2.7 million persons. Genotype D, subtype D7, is predominant and mutations in the precore region of HBV genome are highly prevalent.

This epidemiological situation requires obviously widespread active interventions for prevention and control. In addition, anti‐hepatitis B vaccination programme should be applied with the utmost discipline in the five countries considered in this present review. This systematic review will, hopefully, increase knowledge at disposal of Public Health authorities, enabling better resource allocation and healthcare delivery. The present synthesis intends to stimulate policies aiming at preventing the spread of HBV, keeping in mind that eradication of the virus from Maghrebi populations should be the ultimate objective of Public Health authorities.
Estimation of calf:cow ratios of Pacific walruses for use in population modeling and monitoring
Authors: Citta John J. , Quakenbush Lori T. , Taras Brian D.
Published: February 2013

We report on a method of visually classifying Pacific walruses (Odobenus rosmarus) to sex and age class with the goal of estimating calf:cow ratios. Development of this method began in 1958 by Dr. F. H. Fay and was used during six surveys in the Chukchi Sea between 1981 and 1999. We estimate calf:cow ratios using beta‐binomial models to allow for overdispersion and use Monte Carlo simulations to assess the reliability of prior surveys and quantify sample sizes required for future surveys. Calf:cow ratios did not vary by region, date, or by the number of cows in a group. However, higher ratios were observed in the morning and evening than during the day, indicating haul out behavior of cows varies by reproductive status. Adjusted for solar noon, few calves were observed in 1981 (3:100), 1984 (6:100), and 1998 (5:100), while substantially more were observed in 1982 (15:100) and 1999 (13:100). Classifying between 200 and 300 groups with cows (~1,600–2,300 individual cows) will yield calf:cow ratios with ~20%–30% relative precision. Tagging studies that examine hauling‐out behavior of cows with and without calves relative to time‐of‐day are necessary to better understand how to interpret calf:cow ratios.
Spatiotemporal reconstruction of the Aquilegia rapid radiation through next‐generation sequencing of rapidly evolving cpDNA regions
Authors: Fior Simone , Li Mingai , Oxelman Bengt , Viola Roberto , Hodges Scott A. , Ometto Lino , Varotto Claudio
Published: February 2013

Aquilegia is a well‐known model system in the field of evolutionary biology, but obtaining a resolved and well‐supported phylogenetic reconstruction for the genus has been hindered by its recent and rapid diversification.

Here, we applied 454 next‐generation sequencing to PCR amplicons of 21 of the most rapidly evolving regions of the plastome to generate c. 24 kb of sequences from each of 84 individuals from throughout the genus.

The resulting phylogeny has well‐supported resolution of the main lineages of the genus, although recent diversification such as in the European taxa remains unresolved. By producing a chronogram of the whole Ranunculaceae family based on published data, we inferred calibration points for dating the Aquilegia radiation. The genus originated in the upper Miocene c. 6.9 million yr ago (Ma) in Eastern Asia, and diversification occurred c. 4.8 Ma with the split of two main clades, one colonizing North America, and the other Western Eurasia through the mountains of Central Asia. This was followed by a back‐to‐Asia migration, originating from the European stock using a North Asian route.

These results provide the first backbone phylogeny and spatiotemporal reconstruction of the Aquilegia radiation, and constitute a robust framework to address the adaptative nature of speciation within the group.
Interspecific hybridization in Gossypium L.: characterization of progenies with different ploidy‐confirmed multigenomic backgrounds
Authors: Newaskar Ganesh S. , Chimote Vivek P. , Mehetre Subhash S. , Jadhav Ashok S.
Published: February 2013

Cytological and molecular investigations were undertaken for parent and progeny derived from a trispecific line [2(Gossypium arboreum × G. anomalum) × G. hirsutum var. BWR], which was crossed with G. hirsutum var. JLH168. Cytomorphological analysis of the F1 (G. arboreum × G. anomalum), its amphidiploid and progeny from trispecies hybrid showed distorted ploidy segregation with monovalents to hexavalents and high intergenomic (small A2 and large B1) allosynthetic chromosome pairing. Microsatellite analysis identified three fragments associated with G. arboreum and G. anomalum and six fragments associated with G. hirsutum in derivates of the trispecies line × G. hirsutum var. JLH168. Inter‐Retrotransposon Amplified Polymorphism (IRAP) analysis revealed fragments of G. arboreum and G. anomalum, only in F1 and amphidiploid. Chromosomal association and microsatellite analysis of three progeny genotypes (i.e. haploid, hexaploid and tetraploid no. 1) confirmed that they share multigenomic background from the three cotton species (A2, AhDh and B1 genome). The interspecific hybrid cotton genotypes studied are likely to be useful for the introgression of genes from diploid species to commercial upland cultivars.
The generation of novel species hybrids between garden dahlias and Dahlia macdougallii to increase the gene pool for variety breeding
Authors: Schie Stephan , Debener Thomas
Published: February 2013

To transfer new traits into the gene pool of garden dahlias (Dahlia variabilis), crosses between garden dahlias (2n = 64) and the epiphytic species Dahlia macdougallii (2n = 32) from the section Epiphytum were conducted. Six hybrid plants were obtained. The hybrid status was verified using three SSR markers. In addition, flow cytometry was performed to determine the genome size of the hybrids and to show that the hybrids were hexaploid as expected from crosses between tetraploids and octoploids. The open pollinated progeny of the hybrids produced four progeny with octoploid genomes. The hybrids exhibited indeterminate vegetative growth and the formation of flowers from axillary buds, similar to the father D. macdougallii. This result is of interest for breeding new varieties of dahlia with traits that are not present in the current gene pool.
Domestic Carnivore's Development: Detection of Oct‐4, A Pluripotency Marker, in Pharyngeal Arches
Authors: Roballo KCS , Ercolin ACM , Casals JB , Pieri NCG , Barreto RSN , Illera MJ , Martins DS , Miglino MA , Ambrósio CE
Published: February 2013

Contents

Very few carnivore's embryology is reported mainly restricted to old literature without new technique analyses. Also, their development focuses on pharyngeal arches and stem cell sources and the high capacity for differentiation from those cells to generate embryonic tissue. We aimed to use immunohistochemistry to prove the potentiality of these stem cell niches. The results were to highlight the timetable for the development of dogs and cats, the proper formation of pharyngeal arches and the description of these cells on first and second arches since 17–25 days of pregnancy. After that, the differentiation process is reduced.
Low‐Probability Flood Risk Modeling for New York City
Authors: Aerts Jeroen C. J. H. , Lin Ning , Botzen Wouter , Emanuel Kerry , de Moel Hans
Published: February 2013

The devastating impact by Hurricane Sandy (2012) again showed New York City (NYC) is one of the most vulnerable cities to coastal flooding around the globe. The low‐lying areas in NYC can be flooded by nor'easter storms and North Atlantic hurricanes. The few studies that have estimated potential flood damage for NYC base their damage estimates on only a single, or a few, possible flood events. The objective of this study is to assess the full distribution of hurricane flood risk in NYC. This is done by calculating potential flood damage with a flood damage model that uses many possible storms and surge heights as input. These storms are representative for the low‐probability/high‐impact flood hazard faced by the city. Exceedance probability‐loss curves are constructed under different assumptions about the severity of flood damage. The estimated flood damage to buildings for NYC is between US$59 and 129 millions/year. The damage caused by a 1/100‐year storm surge is within a range of US$2 bn–5 bn, while this is between US$5 bn and 11 bn for a 1/500‐year storm surge. An analysis of flood risk in each of the five boroughs of NYC finds that Brooklyn and Queens are the most vulnerable to flooding. This study examines several uncertainties in the various steps of the risk analysis, which resulted in variations in flood damage estimations. These uncertainties include: the interpolation of flood depths; the use of different flood damage curves; and the influence of the spectra of characteristics of the simulated hurricanes.
Moderating Factors in the Path from Physical Abuse to Attempted Suicide in Adolescents: Application of the Interpersonal‐Psychological Theory of Suicide
Authors: Cero Ian , Sifers Sarah
Published: February 2013

Childhood physical abuse is a major risk factor for suicide attempt, but factors that moderate this risk remain largely unexamined. Moderated mediation analysis was used with 186 adolescents who responded to the Profiles of Student Life: Attitudes and Behavior survey. Physical abuse increased risk directly and indirectly through reduced self‐esteem. Involvement in youth programs moderated the direct effect. Community service moderated the indirect effect. Results indicate 2 hours per week of involvement in youth programs and 2 hours per week of community service mitigated suicide attempt risk associated with abuse. Providing avenues for youth experiencing abuse to increase their community service and involvement is recommended.
Use of antibacterial fixed‐dose combinations in the private sector in eight Latin American Countries between 1999 and 2009
Authors: Wirtz Veronika J. , Mol Peter G. M. , Verdijk Jonneke , Vander Stichele Robert H. , Taxis Katja
Published: February 2013

Objective

To assesses the safety and rationale of antibacterial fixed‐dose combinations in the private sector in Latin America and determine the extent of their use.

Methods

Analysis of FDCs was based on retail sales data for eight Latin American countries (Argentina, Brazil, Chile, Colombia, Mexico, Peru, Uruguay and Venezuela) between 1999 and 2009. FDCs were classified according to the pre‐defined criteria. Use was expressed as daily defined doses per 1000 inhabitants per day (DDD/TID).

Results

A total of 175 antibacterial FDCs contained a mean of 1.3 antibacterial substances and 3.2 other active substances. Thirty‐seven (21%) FDCs were classified as unsafe, 124 (70%) as lacking sufficient evidence for efficacy and only 14 (9%) of all FDCs were considered rational, for example amoxicillin and clavulanic acid. Consumption of unsafe FDCs decreased by 0.011 DDD/TID (95% CI: −0.012 to −0.009) annually, from 0.173 DDD/TID in 1999 to 0.070 DDD/TID in 2009 (overall decrease, 59.7%). Consumption of FDCs lacking sufficient evidence decreased by 30.3% (−0.018 DDD/TID [95% CI: −0.028 to −0.008] annually), while use of rational FDCs increased by 17.1% (from 1.283 DDD/TID to 1.497 DDD/TID annually).

Conclusion

The majority of antibacterial FDCs in the private sector lack therapeutic benefit. Despite the decrease in the consumption of unsafe antibacterials and those lacking sufficient evidence, their use remains high and their marketing does not fit into strategies of prudent use of antibiotics to contain antibacterial resistance.
‘Eventless’ InsP3‐dependent SR‐Ca2+ release affecting atrial Ca2+ sparks
Authors: Horn Tamara , Ullrich Nina D. , Egger Marcel
Published: February 2013

Key points

Inositol 1,4,5‐trisphosphate receptors (InsP3Rs) are functionally expressed in cardiac myocytes.

The influence of inositol 1,4,5‐trisphosphate‐induced sarcoplasmic reticulum (SR)‐Ca2+release (IP3ICR) on atrial excitation‐contraction coupling (ECC) under physiological and pathophysiological conditions remains elusive.

The present study focuses on local IP3ICR and its functional consequences for ryanodine receptor (RyR) activity and subsequent Ca2+‐induced Ca2+ release in atrial myocytes.

Here we show significant SR‐Ca2+ flux, but eventless SR‐Ca2+ release through InsP3Rs.

We suggest a new mechanism based on eventless and highly efficient InsP3‐dependent SR‐Ca2+ flux as a crucial mechanism of functional cross‐talk between InsP3Rs and RyRs, which may be an important factor in the modulation of ECC sensitivity.

Abstract  Augmented inositol 1,4,5‐trisphosphate receptor (InsP3R) function has been linked to a variety of cardiac pathologies, including cardiac arrhythmia. The contribution of inositol 1,4,5‐trisphosphate‐induced Ca2+ release (IP3ICR) in excitation‐contraction coupling (ECC) under physiological conditions, as well as under cellular remodelling, remains controversial. Here we test the hypothesis that local IP3ICR directly affects ryanodine receptor (RyR) function and subsequent Ca2+‐induced Ca2+ release in atrial myocytes. IP3ICR was evoked by UV‐flash photolysis of caged InsP3 under whole‐cell configuration of the voltage‐clamp technique in atrial myocytes isolated from C57/BL6 mice. Photolytic release of InsP3 was accompanied by a significant increase in the Ca2+ release event frequency (4.14 ± 0.72 vs. 6.20 ± 0.76 events (100 μm)−1 s−1). These individual photolytically triggered Ca2+ release events were identified as Ca2+ sparks, which originated from RyR openings. This was verified by Ca2+ spark analysis and pharmacological separation between RyR and InsP3R‐dependent sarcoplasmic reticulum (SR)‐Ca2+ release (2‐aminoethoxydiphenyl borate, xestospongin C, tetracaine). Significant SR‐Ca2+ flux but eventless SR‐Ca2+ release through InsP3R were characterized using SR‐Ca2+ leak/SR‐Ca2+ load measurements. These results strongly support the idea that IP3ICR can effectively modulate RyR openings and Ca2+ spark probability. We conclude that eventless and highly efficient InsP3‐dependent SR‐Ca2+ flux is the main mechanism of functional cross‐talk between InsP3Rs and RyRs, which may be an important factor in the modulation of ECC sensitivity.
Wet etching silicon nanofins with (111)-oriented sidewalls
Authors: Liu Lianci , Kuryatkov Vladimir V. , Nikishin Sergey A. , Harris H. Rusty , Holtz Mark
Published: February 2013

A systematic study of the chemical etching of Si(111) fins is reported. Optimized wet etching of Si(110) with isopropyl alcohol and tetramethyl ammonium hydroxide produces 30 nm wide silicon nanofins with (111)-oriented sidewalls. The addition of a sacrificial silicon wafer for “doping” the etchant reduces the surface roughness of the interfin region. Atomic force microscopy indicates interfin roughness of <2 nm (root-mean square) based on scan areas of 5 μm × 5 μm. The addition of a commercial surfactant helps in reducing the presence of shoulders where the (111) and (110) crystallographic surfaces meet. Smooth sidewalls are obtained as a consequence of the directional etching process. Using electron-beam lithography and SiO2 as a hard mask, fin aspect ratio of >8:1 with 30 nm wide fins is achieved.
Identifying the Goldilocks Model
Authors: VanHook Annalisa M.
Published: February 2013

Computational methods can be used to identify models that are neither too simple nor too complex to be accurate.
Pharmacodynamics and Dose-Response Relationships of Liposomal Amphotericin B against Different Azole-Resistant Aspergillus fumigatus Isolates in a Murine Model of Disseminated Aspergillosis
Authors: Seyedmousavi Seyedmojtaba , Melchers Willem J. G. , Mouton Johan W. , Verweij Paul E.
Published: February 2013

The management of invasive aspergillosis (IA) has become more complicated due to the emergence of acquired azole resistance in
Aspergillus fumigatus
, which is associated with treatment failure and a mortality rate of 88%. Treatment with liposomal amphotericin B (L-AmB) may be a useful alternative to improve therapeutic outcome in azole-resistant IA. Four clinical
A. fumigatus
isolates obtained from patients with proven IA were studied in a nonneutropenic murine model of infection: a wild-type isolate without mutations in the
cyp51A
gene and three azole-resistant isolates harboring a single mutation at codon 220 (M220I) and tandem repeat mutations (a 34-bp tandem repeat mutation in the promoter region of the
cyp51A
gene in combination with substitutions at codon L98 [TR
34
/L98H] and a 46-bp tandem repeat mutation in the promoter region of the
cyp51A
gene in combination with mutation at codons Y121 and T289 [TR
46
/Y121F/T289A]), respectively. Female CD-1 mice were infected intravenously 24 h prior to the start of therapy. Groups of 11 mice were treated at days 1, 2, and 5 postchallenge with increasing 4-fold doses of L-AmB ranging from 0.004 to 16 mg/kg/day and observed for 14 days. Survival for all 4 isolates at day 14 was significantly better than that of controls. A dose-response relationship was observed independent of the azole resistance mechanism. The Hill-type model with a variable slope fitted the relationship between the dose and 14-day survival well for all isolates, with
R
2
values of 0.95 (wild-type), 0.97 (M220I), 0.85 (TR
34
/L98H), and 0.94 (TR
46
/Y121F/T289A), respectively. Multiple logistic regression analysis confirmed that there was no significant difference between groups. The results of these experiments indicate that L-AmB was able to prolong survival
in vivo
in disseminated IA independent of the presence of an azole resistance mechanism in a dose-dependent manner, and therefore, they support a role for L-AmB in the treatment of azole-resistant IA.
Candida albicans Flu1-Mediated Efflux of Salivary Histatin 5 Reduces Its Cytosolic Concentration and Fungicidal Activity
Authors: Li Rui , Kumar Rohitashw , Tati Swetha , Puri Sumant , Edgerton Mira
Published: February 2013

Histatin 5 (Hst 5) is a salivary human antimicrobial peptide that is toxic to the opportunistic yeast
Candida albicans
. Fungicidal activity of Hst 5 requires intracellular translocation and accumulation to a threshold concentration for it to disrupt cellular processes. Previously, we observed that total cytosolic levels of Hst 5 were gradually reduced from intact cells, suggesting that
C. albicans
possesses a transport mechanism for efflux of Hst 5. Since we identified
C. albicans
polyamine transporters responsible for Hst 5 uptake, we hypothesized that one or more polyamine efflux transporters may be involved in the efflux of Hst 5.
C. albicans FLU1
and
TPO2
were found to be the closest homologs of
Saccharomyces cerevisiae TPO1
, which encodes a major spermidine efflux transporter, indicating that the products of these two genes may be involved in efflux of Hst 5. We found that
flu1
Δ/Δ cells, but not
tpo2
Δ/Δ cells, had significant reductions in their rates of Hst 5 efflux and had significantly higher cytoplasmic Hst 5 and Hst 5 susceptibilities than did the wild type. We also found that
flu1
Δ/Δ cells had reduced biofilm formation compared to wild-type cells in the presence of Hst 5. Transcriptional levels of
FLU1
were not altered over the course of treatment with Hst 5; therefore, Hst 5 is not likely to induce
FLU1
gene overexpression as a potential mechanism of resistance. Thus, Flu1, but not Tpo2, mediates efflux of Hst 5 and is responsible for reduction of its toxicity in
C. albicans
.
Antimicrobial Activity of Ceftaroline-Avibactam Tested against Clinical Isolates Collected from U.S. Medical Centers in 2010-2011
Authors: Sader Helio S. , Flamm Robert K. , Jones Ronald N.
Published: February 2013

Ceftaroline-avibactam and comparator agents were tested by the broth microdilution method against 20,089 isolates consecutively collected in 2010 and 2011 from 75 U.S. medical centers. Ceftaroline-avibactam was active against
Enterobacteriaceae
(4,908 strains; MIC
90
, 0.25 μg/ml; highest MIC, 4 μg/ml), including meropenem-nonsusceptible
Klebsiella
spp. and ceftazidime-nonsusceptible
Enterobacter cloacae
strains (MIC
90
, 1 μg/ml for both). Ceftaroline-avibactam was also active against ceftriaxone-nonsusceptible
Streptococcus pneumoniae
(MIC
90
, 0.25 μg/ml) and methicillin-resistant
Staphylococcus aureus
(MIC
90
, 1 μg/ml).
Drug Repurposing Screen Reveals FDA-Approved Inhibitors of Human HMG-CoA Reductase and Isoprenoid Synthesis That Block Cryptosporidium parvum Growth
Authors: Bessoff Kovi , Sateriale Adam , Lee K. Kyungae , Huston Christopher D.
Published: February 2013

Cryptosporidiosis, a diarrheal disease usually caused by
Cryptosporidium parvum
or
Cryptosporidium hominis
in humans, can result in fulminant diarrhea and death in AIDS patients and chronic infection and stunting in children. Nitazoxanide, the current standard of care, has limited efficacy in children and is no more effective than placebo in patients with advanced AIDS. Unfortunately, the lack of financial incentives and the technical difficulties associated with working with
Cryptosporidium
parasites have crippled efforts to develop effective treatments. In order to address these obstacles, we developed and validated (Z′ score = 0.21 to 0.47) a cell-based high-throughput assay and screened a library of drug repurposing candidates (the NIH Clinical Collections), with the hopes of identifying safe, FDA-approved drugs to treat cryptosporidiosis. Our screen yielded 21 compounds with confirmed activity against
C. parvum
growth at concentrations of <10 μM, many of which had well-defined mechanisms of action, making them useful tools to study basic biology in addition to being potential therapeutics. Additional work, including structure-activity relationship studies, identified the human 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor itavastatin as a potent inhibitor of
C. parvum
growth (50% inhibitory concentration [IC
50
] = 0.62 μM). Bioinformatic analysis of the
Cryptosporidium
genomes indicated that the parasites lack all known enzymes required for the synthesis of isoprenoid precursors. Additionally, itavastatin-induced growth inhibition of
C. parvum
was partially reversed by the addition of exogenous isopentenyl pyrophosphate, suggesting that itavastatin reduces
Cryptosporidium
growth via on-target inhibition of host HMG-CoA reductase and that the parasite is dependent on the host cell for synthesis of isoprenoid precursors.
Promoter Polymorphisms in the ATP Binding Cassette Transporter Gene Influence Production of Cell-Derived Microparticles and Are Highly Associated with Susceptibility to Severe Malaria in Humans
Authors: Sahu Upasana , Mohapatra Biranchi N. , Kar Shantanu K. , Ranjit Manoranjan
Published: February 2013

Microparticle (MP) efflux is known to be mediated by the ABCA1 protein, and the plasma level of these cell-derived MPs is elevated considerably during human malarial infection. Therefore, two polymorphisms at positions −477 and −320 in the promoter of the ABCA1 gene were genotyped and tested for association with the plasma MP level in four groups of malaria patients segregated according to the clinical severity, i.e., cerebral malaria (CM), multiorgan dysfunction (MOD), noncerebral severe malaria, and uncomplicated malaria (UM). The TruCount tube-based flow cytometric method was used for the exact quantification of different cell-derived MPs in patients. Polymorphisms in the ABCA1 gene promoter were analyzed by use of the PCR/two-primer-pair method, followed by restriction fragment length polymorphism, in 428 malaria patients. The level of circulating plasma MPs was significantly higher in febrile patients with
Plasmodium falciparum
infection, especially in CM patients compared to healthy individuals. The homozygous wild-type −477 and −320 genotype was observed to be significantly higher in patients with severe malaria. These patients also showed marked increases in the plasma MP numbers compared to UM patients. We report here for the first time an association of ABCA1 promoter polymorphisms with susceptibility to severe malaria, especially to CM and MOD, indicating the protective effect of the mutant variant of the polymorphism. We hypothesize that the −477T and −320G polymorphisms affect the downregulation of MP efflux and may be a predictor of organ complication during
P. falciparum
malarial infections.
5-Lipoxygenase Activity Increases Susceptibility to Experimental Paracoccidioides brasiliensis Infection
Authors: Tristão Fabrine Sales Massafera , Rocha Fernanda Agostini , Moreira Ana Paula , Cunha Fernando Queiroz , Rossi Marcos Antonio , Silva João Santana
Published: February 2013

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the thermodimorphic fungus
Paracoccidioides brasiliensis
. Leukotrienes and lipoxins are lipid mediators produced after 5-lipoxygenase (5-LO) activation that exhibit pro- and anti-inflammatory roles, respectively. Here, we have investigated the contribution of 5-LO enzymatic activity in PCM using an experimental model of
P. brasiliensis
infection. B6.129 wild-type (B6.129) and 5-LO-deficient (5-LO
−/−
) mice were intravenously inoculated with a virulent strain of
P. brasiliensis
(Pb18), and the survival rate of the infected mice was investigated on different days after yeast infection. 5-LO
−/−
mice exhibited an increased survival rate associated with a decreased number of CFU. The resistance of 5-LO
−/−
during PCM was associated with augmented nitric oxide (NO) production and the formation of compact granulomas. In addition, the absence of 5-LO was associated with a diminished number of CD4
+
CD25
+
regulatory T cells, higher levels of gamma interferon and interleukin-12, and increased T-bet (a T-box transcription factor that directs Th1 lineage commitment) mRNA levels in the lungs. Taken together, our results show for the first time that 5-LO enzymatic activity increases susceptibility to
P. brasiliensis
, suggesting that this pathway may be a potential target for therapeutic intervention during PCM.
MRSA infected emphysematous bullae in an asymptomatic COPD patient
Authors: Zaman Shahriar Raj
Published: February 2013

This is a case of a 57-year-old gentleman with a history of chronic obstructive pulmonary disease (COPD) who presented with diarrhoea of more than 4 weeks in length. On chest x-ray, he was incidentally found to have a large cavitating lesion in his right lung. He denied having any respiratory distress at any stage and clinically he had been completely asymptomatic. The CT-guided biopsy confirmed a methicillin-resistantStaphylococcus aureuspositive lung cavitation, most likely secondary to his poor dentition. A full dental clearance was performed, and he was treated with a course of intravenous vancomycin and oral clindamycin with good effect.
Brainstem anaplastic glioma in patients with AIDS: a case report and review of the literature
Authors: Chaudhry Nauman S , Ahmad Faiz U , Blieden Clifford , Benveniste Ronald J
Published: February 2013

AIDS is an increasingly common diagnosis seen by neurologists and neurosurgeons alike. Although the more common brain lesions associated with AIDS are due to central nervous system lymphomas, toxoplasma encephalitis or progressive multifocal leukoencephalopathy, relatively recent clinical evidence has shown that AIDS-independent cerebral tumours can arise as well, albeit less commonly. Previous incidents have been reported with HIV and AIDS patients presenting with cerebral astrocytomas. To our knowledge, there has never been a report in the literature of a brainstem anaplastic glioma occurring in an AIDS or HIV patient. We report a 55-year-old patient with HIV and brainstem anaplastic glioma. Its presentation, diagnostic difficulty, scans, histology and subsequent treatment are discussed. We also review the relevant literature on gliomas in HIV/AIDS patients.
Transient right-to-left intracardiac shunt following a right ventricular myocardial infarction
Authors: Krishnamurthy Arvindra , White Hazel , Ahmed Rizwan
Published: February 2013

A 56-year-old smoker presented with a 3-day history of intermittent chest pain. Cardiovascular examination on admission was normal. ECG showed minimal (<1 mm) ST elevation in lead III, and right-sided leads revealed similar mild ST-elevation. Troponin I was elevated at 10.91. He was managed as a delayed-presentation ST-elevation myocardial infarction case. 12 h following admission, he developed oxygen-resistant hypoxia and hypotension. There were no clinical or radiological signs of pulmonary congestion. CT pulmonary angiogram revealed no pulmonary embolus. A bubble-contrast echocardiogram confirmed an active interatrial right-to-left shunt without Valsalva provocation. His hypoxia steadily improved over the following 24 h and he did not require any shunt closure. A repeat bubble contrast echocardiogram showed that the shunt was now only active following a Valsalva manoeuvre. Transoesophageal echocardiography confirmed a patent foramen ovale. This is a rare but important cause of resistant hypoxia following a right-heart infarct.
Dynamics and stability: epigenetic conversions in position effect variegation
Authors: Yankulov Krassimir
Published: February 2013

Position effect variegation (PEV) refers to quasi-stable patterns of gene expression that are observed at specific loci throughout the genomes of eukaryotes. The genes subjected to PEV can be completely silenced or fully active. Stochastic conversions between these 2 states are responsible for the variegated phenotypes. Positional variegation is used by human pathogens (Trypanosoma, Plasmodium, and Candida) to evade the immune system or adapt to the host environment. In the yeasts Saccharomyces cerevisiae and S accharomyces pombe, telomeric PEV aids the adaptation to a changing environment. In metazoans, similar epigenetic conversions are likely to accompany cell differentiation and the setting of tissue-specific gene expression programs. Surprisingly, we know very little about the mechanisms of epigenetic conversions. In this article, earlier models on the nature of PEV are revisited and recent advances on the dynamic nature of chromatin are reviewed. The normal dynamic histone turnover during transcription and DNA replication and its perturbation at transcription and replication pause sites are discussed. It is proposed that such perturbations play key roles in epigenetic conversions and in PEV.
The 4d–4p transitions and soft X-ray laser wavelengths in Si-like ions
Authors: El-Maaref A. Abou , Uosif M.A.M. , Allam S.H. , El-Sherbini Th.M.
Published: February 2013

The transitions between 4p and 4d levels have been studied to examine the possibility of laser wavelength production in the soft X-ray region. The oscillator strengths of the transitions 3p4p (3S,3P,3D) → 3p4d (3Po,3Do,3Fo) have been calculated using CIV3 code. Using calculated oscillator strengths, the excitation rate coefficients, reduced populations, and gain coefficients for Si-like Ni XV, Zn XVII, Ga XVIII, Ge XIX, and As XX at electron temperatures 1/4, 1/2, and 3/4 the ionization potential have been calculated. The method by Palumbo and Elton has been used in the calculation of laser parameters. The present calculated data show promising values for the production of laser wavelengths in the soft X-ray region. The maximum values of the gain factor lie within the range α ∼ 109 cm−1 and wavelength λ ≤ 469 Å.
THE SUYAMA–YAMAGUCHI CONSISTENCY RELATION IN THE PRESENCE OF VECTOR FIELDS
Authors: BELTRÁN ALMEIDA JUAN P. , RODRÍGUEZ YEINZON , VALENZUELA-TOLEDO CÉSAR A.
Published: February 2013

We consider inflationary models in which vector fields (VF) are responsible for part or eventually all of the primordial curvature perturbation ζ. Such models are phenomenologically interesting since they naturally introduce anisotropies in the probability distribution function of the primordial fluctuations that can leave a measurable imprint in the cosmic microwave background. Assuming that non-Gaussianity (NG) is generated due to the superhorizon evolution, we use the δN formalism to do a complete tree level calculation of the NG parameters f NL and τ NL in the presence of VF. We isolate the isotropic pieces of the NG parameters, which anyway have contributions from the VF, and show that they obey the Suyama–Yamaguchi (SY) consistency relation [Formula: see text]. Other ways of defining the NG parameters, which could be observationally relevant, are stated and the respective SY-like consistency relations are obtained.
COMBINING VELOCITY AND LOCATION-SPECIFIC SPATIAL CLUES IN TRAJECTORIES FOR COUNTING CROWDED MOVING OBJECTS
Authors: HASHEMZADEH MAHDI , PAN GANG , WANG YUEMING , YAO MIN , WU JIAN
Published: February 2013

Trajectory-clustering-based methods have shown a good performance in counting moving objects in densely crowded scenes. However, they still fall into trouble in complex scenes, such as with the close proximity of moving objects, freely moving parts of objects, and different object size in different locations of the scene. This paper proposes a new method combining velocity and location-specific spatial clues in trajectories to deal with these problems. We first extract the velocities of a trajectory over its life-time. To alleviate confusion around the boundary regions between close objects, extracted velocity information is utilized to eliminate unreal-world feature points on objects' boundaries. Then, a function is introduced to measure the similarity of the trajectories integrating both of the spatial and the velocity clues. This function is employed in the Mean-Shift clustering procedure to reduce the effect of freely moving parts of the objects. To address the problem of various object sizes in different regions of the scene, we suggest a technique to learn the location-specific size distribution of objects in different locations of a scene. The experimental results show that our proposed method achieves a good performance. Compared with other trajectory-clustering-based methods, it decreases the counting error rate by about 10%.
SHAPE AND TEXTURE INDEXES APPLICATION TO CELL NUCLEI CLASSIFICATION
Authors: THIBAULT GUILLAUME , FERTIL BERNARD , NAVARRO CLAIRE , PEREIRA SANDRINE , CAU PIERRE , LEVY NICOLAS , SEQUEIRA JEAN , MARI JEAN-LUC
Published: February 2013

This paper describes the sequence of construction of a cell nuclei classification model by the analysis, the characterization and the classification of shape and texture. We describe first the elaboration of dedicated shape indexes and second the construction of the associated classification submodel. Then we present a new method of texture characterization, based on the construction and the analysis of statistical matrices encoding the texture. The various characterization techniques developed in this paper are systematically compared to previous approaches. In particular, we paid special attention to the results obtained by a versatile classification method using a large range of descriptors dedicated to the characterization of shapes and textures. Finally, the last classifier built with our methods achieved 88% of classification out of the 94% possible.
FAULT DETECTION AND INTERVENTION IN BIOLOGICAL FEEDBACK NETWORKS
Authors: LAYEK RITWIK , DATTA ANIRUDDHA
Published: February 2013

The study of diseases such as cancer requires the modeling of gene regulations and the loss of control associated with it. Prior work has shown that the genetic alterations in the system can be suitably modeled using different fault models (like stuck-at faults) in the Boolean Network paradigm. By studying the dynamics of the original and the faulty BN, it is possible to design intervention strategies which could drive the system from a diseased state to a less harmful one. In this paper, the method of detecting faults along with the intervention design demonstrated on a couple of real biological pathways (DNA damage pathways and osmotic stress response pathways).
BIOACTIVITY OF APATITE–WOLLASTONITE GLASS-CERAMICS PRODUCED BY MELTING CASTING
Authors: PARK JONGEE , OZTURK ABDULLAH
Published: February 2013

Glass-ceramics containing only apatite and wollastonite crystals were produced in the system MgO-CaO-SiO2-P2O5-F by the melt casting process. The bioactivity of the glass-ceramics was determined by immersing the glass-ceramics in a simulated body fluid (SBF) and by assessing the resulting apatite formation on the free surface after various immersion durations. A 12-μm-thick apatite layer formed on the surface of the glass-ceramic containing only apatite crystals after 20 days immersion in SBF. However, the thickness of the apatite layer formed on the surface of the glass-ceramic containing apatite and wollastonite crystals was 1 μm. Results have shown that the bioactivity of glass-ceramic depends strongly on the type of crystal(s) developed during the glass-ceramic process and their proportion in the glassy matrix.
CHAOTIC VIBRATIONS IN FUNCTIONALLY GRADED DOUBLY CURVED SHELLS WITH INTERNAL RESONANCE
Authors: ALIJANI F. , AMABILI M.
Published: February 2013

Chaotic vibrations of functionally graded doubly curved shells subjected to concentrated harmonic load are investigated. It is assumed that the shell is simply supported and the edges can move freely in in-plane directions. Donnell's nonlinear shallow shell theory is used and the governing partial differential equations are obtained in terms of shell's transverse displacement and Airy's stress function. By using Galerkin's procedure, the equations of motion are reduced to a set of infinite nonlinear ordinary differential equations with cubic and quadratic nonlinearities. A bifurcation analysis is carried out and the discretized equations are integrated at (i) fixed excitation frequencies and variable excitation amplitudes and (ii) fixed excitation amplitudes and variable excitation frequencies. In particular, Gear's backward differentiation formula (BDF) is used to obtain bifurcation diagrams, Poincaré maps and time histories. Furthermore, maximum Lyapunov exponent and Lyapunov spectrum are obtained to classify the rich dynamics. It is revealed that the shell may exhibit complex behavior including sub-harmonic, quasi-periodic and chaotic response when subjected to large harmonic excitations.
PSEUDO-Q-SYMMETRIC RIEMANNIAN MANIFOLDS
Authors: MANTICA CARLO ALBERTO , SUH YOUNG JIN
Published: February 2013

In this paper, we introduce a new kind of tensor whose trace is the well-known Z tensor defined by the present authors. This is named Q tensor: the displayed properties of such tensor are investigated. A new kind of Riemannian manifold that embraces both pseudo-symmetric manifolds ( PS )n and pseudo-concircular symmetric manifolds [Formula: see text] is defined. This is named pseudo-Q-symmetric and denoted with ( PQS )n. Various properties of such an n-dimensional manifold are studied: the case in which the associated covector takes the concircular form is of particular importance resulting in a pseudo-symmetric manifold in the sense of Deszcz [On pseudo-symmetric spaces, Bull. Soc. Math. Belgian Ser. A44 (1992) 1–34]. It turns out that in this case the Ricci tensor is Weyl compatible, a concept enlarging the classical Derdzinski–Shen theorem about Codazzi tensors. Moreover, it is shown that a conformally flat ( PQS )n manifold admits a proper concircular vector and the local form of the metric tensor is given. The last section is devoted to the study of ( PQS )n space-time manifolds; in particular we take into consideration perfect fluid space-times and provide a state equation. The consequences of the Weyl compatibility on the electric and magnetic part of the Weyl tensor are pointed out. Finally a ( PQS )n scalar field space-time is considered, and interesting properties are pointed out.
ON THE DISPERSIVE WAVE DYNAMICS OF 2 × 2 RELAXATION SYSTEMS
Authors: AURSAND PEDER , FLÅTTEN TORE
Published: February 2013

We consider hyperbolic conservation laws with relaxation terms. By studying the dispersion relation of the solution of general linearized 2 × 2 hyperbolic relaxation systems, we investigate in detail the transition between the wave dynamics of the homogeneous relaxation system and that of the local equilibrium approximation. We establish that the wave velocities of the Fourier components of the solution to the relaxation system will be monotonic functions of a stiffness parameter φ = εξ, where ε is the relaxation time and ξ is the wave number. This allows us to extend in a natural way the classical concept of the sub-characteristic condition into a more general transitional sub-characteristic condition. We further identify two parameters β and γ that characterize the behavior of such general 2 × 2 linear relaxation systems. In particular, these parameters define a natural transition point, representing a value of φ where the dynamics will change abruptly from being equilibrium-like to behaving more like the homogeneous relaxation system. Herein, the parameter γ determines the location of the transition point, whereas β measures the degree of smoothness of this transition.