bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of PU.1‐linked TLR4 expression by cilostazol with decrease of cytokine production in macrophages from patients with rheumatoid arthritis
Authors: Park SY , Lee SW , Baek SH , Lee CW , Lee WS , Rhim BY , Hong KW , Kim CD
Published: October 2012

Background and Purpose

The present study assessed the effects of cilostazol on LPS‐stimulated TLR4 signal pathways in synovial macrophages from patients with rheumatoid arthritis (RA). These effects were confirmed in collagen‐induced arthritis (CIA) in mice.

Experimental Approach

Expression of TLR4, PU.1, NF‐κB p65 and IκBα on synovial fluid macrophages from RA patients was determined by Western blotting, and cytokines were measured by elisa. Anti‐arthritic effects were evaluated in CIA mice.

Key Results

Intracellular cAMP was concentration‐dependently raised by cilostazol (1–100 μM). Cilostazol significantly suppressed LPS‐stimulated increase of TLR4 expression by blocking PU.1 transcriptional activity in RA macrophages. In addition, cilostazol decreased LPS‐induced myeloid differentiation factor 88 (MyD88) expression, but not that of TNF receptor‐associated factor 6 (TRAF6). Cilostazol also suppressed IkBα degradation and NF‐κB p65 nuclear translocation. Moreover, LPS‐induced increase of cytokine production (TNF‐α, IL‐1β) was inhibited by cilostazol, an effect which was accompanied by suppression of IκBα degradation, and NF‐κB p65 nuclear translocation. However, expression of anti‐inflammatory IL‐10 was elevated by cilostazol and forskolin/IBMX. In mice with CIA, post‐treatment with cilostazol (30 mg kg−1 day−1) decreased expression of TLR4 in knee joints in association with decreased recruitment of macrophages. Consequently, synovial inflammation, proteoglycan depletion and bone erosion were significantly inhibited by cilostazol treatment.

Conclusions and Implications

Cilostazol down‐regulated LPS‐stimulated PU.1‐linked TLR4 expression and TLR4/MyD88/NF‐κB signal pathways, and then suppressed inflammatory cytokine production in synovial macrophages from RA patients. Also cilostazol markedly inhibited the severity of CIA in mice.
To B or not to B cells-mediate a healthy start to life
Authors: Nguyen T G , Ward C M , Morris J M
Published: October 2012

Maternal immune responses during pregnancy are critical in programming the future health of a newborn. The maternal immune system is required to accommodate fetal immune tolerance as well as to provide a protective defence against infections for the immunocompromised mother and her baby during gestation and lactation. Natural immunity and antibody production by maternal B cells play a significant role in providing such immunoprotection. However, aberrations in the B cell compartment as a consequence of maternal autoimmunity can pose serious risks to both the mother and her baby. Despite their potential implication in shaping pregnancy outcomes, the role of B cells in human pregnancy has been poorly studied. This review focuses on the role of B cells and the implications of B cell depletion therapy in pregnancy. It highlights the evidence of an association between aberrant B cell compartment and obstetric conditions. It also alludes to the potential mechanisms that amplify these B cell aberrances and thereby contribute to exacerbation of some maternal autoimmune conditions and poor neonatal outcomes. Clinical and experimental evidence suggests strongly that maternal autoantibodies contribute directly to the pathologies of obstetric and neonatal conditions that have significant implications for the lifelong health of a newborn. The evidence for clinical benefit and safety of B cell depletion therapies in pregnancy is reviewed, and an argument is mounted for further clinical evaluation of B cell-targeted therapies in high-risk pregnancy, with an emphasis on improving neonatal outcomes and prevention of neonatal conditions such as congenital heart block and fetal/neonatal alloimmune thrombocytopenia.
Efficiency of immunoglobulin G replacement therapy in common variable immunodeficiency: correlations with clinical phenotype and polymorphism of the neonatal Fc receptor
Authors: Gouilleux-Gruart V , Chapel H , Chevret S , Lucas M , Malphettes M , Fieschi C , Patel S , Boutboul D , Marson M-N , Gérard L , Lee M , Watier H , Oksenhendler E ,   DEFI study group
Published: October 2012

Treatment of common variable immunodeficiency disorders (CVID) is based on replacement therapy using intravenous (i.v.) or subcutaneous (s.c.) immunoglobulin (Ig)G. Interindividual variation of IgG dose is common. A total of 380 CVID patients on stable IgG replacement from two prospective cohorts were analysed. An ‘efficiency’ index was defined as the ratio of serum IgG trough level minus IgG residual to the average weekly dose of IgG infusion. A reduced efficiency of IgG was associated independently with the i.v. route (P < 0·001) and with the presence of at least one CVID disease-related phenotype (lymphoproliferation, autoimmune cytopenia or enteropathy) (P < 0·001). High IgG efficiency was noted in patients homozygotes for the variable number tandem repeat (VNTR) 3/3 polymorphism of the neonatal Fc receptor gene [IgG Fc fragment receptor transporter alpha chain (FCGRT)] promoter, and this was particularly significant in patients treated with IVIG (P < 0.01). In a multivariate analysis, FCGRT VNTR 3/3 genotype (P = 0·008) and high serum albumin (P < 0·001) were associated independently with increased efficiency of i.v. Ig.
Monozygotic twins discordant for submicroscopic chromosomal anomalies in 2p25.3 region detected by array CGH
Authors: Rio M , Royer G , Gobin S , de Blois MC , Ozilou C , Bernheim A , Nizon M , Munnich A , Bonnefont J‐P , Romana S , Vekemans M , Turleau C , Malan V
Published: October 2012

Although discordant phenotypes in monozygotic twins with developmental disorder are not an exception, underlying genetic discordance is rarely reported. Here, we report on the clinical and cytogenetic details of 4‐year‐old female monozygotic twins with discordant phenotypes. Twin 1 exhibited global developmental delay, overweight and hyperactivity. Twin 2 had an autistic spectrum disorder. Molecular karyotyping in twin 1 identified a 2p25.3 deletion, further confirmed by Fluorescence in situ hybridization (FISH) analysis on leukocytes. Interestingly, array comparative genomic hybridization was normal in twin 2 but FISH analysis using the same probe as twin 1 showed mosaicism with one‐third of cells with a 2p25.3 deletion, one‐third of cells with a 2p25.3 duplication, and one‐third of normal cells. Genotyping with microsatellite markers confirmed the monozygosity of the twins. We propose that the chromosome imbalance may be due to a mitotic non‐allelic recombination occurring during blastomeric divisions of a normal zygote. Such event will result in three distinct cell populations, whose proportion in each embryo formed after separation from the zygote may differ, leading to discordant chromosomal anomalies between twins. We also discuss that the MYTL1L and the SNTG2 genes within the reported region could probably relate to the phenotypic discordance of the monozygotic twins.
Evaluating the utility of ambulatory blood pressure monitoring in kidney transplant recipients
Authors: Wen Kevin C. , Gourishankar Sita
Published: October 2012

Hypertension is a major risk factor for graft dysfunction and cardiovascular disease in kidney transplant recipients (KTX). Accurate monitoring is therefore essential to provide optimal therapy. We evaluated whether 24‐h ambulatory blood pressure monitoring (ABPM) is superior to clinic blood pressure (CBP) measurement in prevalent KTX. Twenty‐four‐hour ABPM was performed in 244 prevalent KTX. The average clinic systolic blood pressure (SBP) was 137.1 ± 19.4 mm Hg, and diastolic blood pressure (DBP) was 79.9 ± 10.5 mm Hg. The ABPM average SBP was 131.3 ± 15.4 mm Hg and DBP was 75.37 ± 8.8 mm Hg; daytime ABPM average SBP was 133.5 ± 15.0 mm Hg and DBP 77.4 ± 9.1 mm Hg. The correlations between CBP, 24‐h ABPM, and daytime ABPM were approximately 0.5. CBP measurements overestimate both 24‐h and daytime ABPM by linear regression (p < 0.001). In this largest study to date evaluating blood pressure monitoring in KTX, we found that CBP overestimates ABPM, highlighting the prevalence of white coat hypertension. The improved accuracy of ABPM will decrease overprescribing of BP medications to avoid hypotension, drug interactions, and non‐adherence. In contrast, identifying the nocturnal “non‐dippers”, not evident by CBP, facilitates appropriate management, as under‐treatment of hypertension could lead to accelerated graft dysfunction, cardiovascular disease, and mortality. These data suggest the improved accuracy of 24‐h ABPM is beneficial for BP monitoring in KTX recipients.
The long‐term efficacy of nucleos(t)ide analog plus a year of low‐dose HBIG to prevent HBV recurrence post‐liver transplantation
Authors: Tanaka Tomohiro , Benmousa Ali , Marquez Max , Therapondos George , Renner Eberhard L. , Lilly Leslie B.
Published: October 2012

Hepatitis B immunoglobulin (HBIG), given in combination with nucleos(t)ide therapy, has reduced the rate of recurrent hepatitis B virus (HBV) following liver transplantation (LT), although the most effective protocol is unknown. We have retrospectively evaluated the use of long‐term nucleos(t)ide analog in combination with one yr of low‐dose HBIG. One hundred and fifty‐two adults with HBV‐related liver disease underwent LT in our center from January 1999 to August 2009; of these, 132 patients who received one yr of HBIG combined with long‐term nucleos(t)ide analogs (largely on lamivudine [LAM] alone, n = 97) afterward were included for the purposes of this study. Median follow‐up post‐transplantation was 1752 d. Patient survival was 93.9%, 86.9% and 84.1% at 1, 5, and 10 yr, respectively; none of the 17 deceased patients had recurrent HBV. HBV recurrence was observed in nine patients (all received LAM+HBIG), yielding recurrence rates of 2.3%, 5.1%, and 8.6% at 1, 3, and 5/10 yr, respectively. All recurrences were successfully managed, usually with additional antiviral treatment. In conclusion, this study, with its long‐term follow‐up, demonstrates that short course of low‐dose HBIG (without anti‐HBs monitoring) combined with the use of long‐term nucleos(t)ide analog is effective and less cumbersome than many protocols in current use.
Acute kidney injury following living donor liver transplantation
Authors: Inoue Yusuke , Soyama Akihiko , Takatsuki Mitsuhisa , Hidaka Masaaki , Muraoka Izumi , Kanematsu Takashi , Eguchi Susumu
Published: October 2012

Background

Although acute kidney injury (AKI) is regarded as a frequent complication following deceased donor liver transplantation, the incidence of AKI following living donor partial liver transplantation (LDLT) has not yet been sufficiently investigated.

Patients and Methods

we used two definitions and investigated the influence of AKI on patient and graft survival. The definitions for the degree of AKI were as follows: AKI 1 was characterized by an increase in serum creatinine of 0.5 mg/dL, while AKI 2 was 1.0 mg/dL above the baseline within one wk during the post‐operative course. The incidence and its impact were investigated.

Results

The incidence of AKI 1 was 63.1%. The development of AKI 1 was correlated with intra‐operative blood loss (p = 0.013), the length of post‐operative ICU stay, and hospitalization (p = 0.020 and 0.038). The incidence of AKI 2 was 27.7%, and AKI 2 was correlated with the length of both the post‐operative ICU and hospital stays. The development of AKI 2 was significantly correlated with graft survival (p = 0.015).

Conclusion

Recognizing the peri‐operative risk and development of AKI is important, because AKI post‐LDLT is associated with a poorer graft survival and a possible worse long‐term prognosis.
Distinctive Frequencies of +874T/A IFN‐γ Gene Polymorphism in a Healthy Serbian Population
Authors: Popadic Dusan , Savic Emina , Spuran Zorica , Markovic Milos , Stojkovic Marija Mostarica , Ramic Zorica , Pravica Vera
Published: October 2012

Purpose: Single nucleotide polymorphism (SNP) in IFN‐γ gene (+874T/A) that determines high (TT), low (AA), and intermediate (TA) responder phenotypes has shown associations with susceptibility to infectious and chronic inflammatory diseases, as well as disease outcome. Therefore, the susceptibility to and outcome of certain diseases can vary in different ethnic populations partially due to the notable differences in frequencies of genotypes and alleles between them. The aim of this study was to determine the distribution of +874T/A genotype and allele frequencies in a healthy Serbian population as a reference for further disease association studies.

Materials and Methods: Genomic DNA samples from 166 healthy volunteers were evaluated for IFN‐γ SNP at position +874 using TaqMan SNP genotyping assay.

Results: The frequencies of AA, AT, and TT genotypes were 28.9%, 49.4%, and 21.7%, respectively. The A and T allele frequencies were 53.6% and 46.4%.

Conclusions: Analysis of genotype and allele frequencies for IFN‐γ+874T/A SNP in healthy subjects revealed, for the first time, the genetic profile for this polymorphism in a Serbian population resembling most European populations, but differing from some Asian and African ethnic groups. Clin Trans Sci 2012; Volume 5: 461–463
The CTSA as an Exemplar Framework for Developing Multidisciplinary Translational Teams
Authors: Calhoun William J. , Wooten Kevin , Bhavnani Suresh , Anderson Karl E. , Freeman Jean , Brasier Allan R.
Published: October 2012

Translational science requires that scientists from multiple disciplines work together to improve the prevention, diagnosis, and treatment of human disease. Although a literature exists on the design and management of multidisciplinary teams, little has been written on multidisciplinary translational teams (MTTs). MTTs are distinct hybrid entities, with goals taken from both industry and academic models. We identified 30 design factors in 10 domains from a literature survey relevant to our MTT model: specific goals, structures, and processes. These dimensions were adapted to our own institutional environment in the selection and management of 11 MTTs that exploited resources of University of Texas Medical Branch (UTMB) Clinical and Translational Sciences Awards (CTSA). Case illustrations of two specific MTTs illustrate some of the challenges encountered and opportunities realized in terms of education and scientific advances. Network depiction of disciplinarity indicated that CTSA KRs and CTSA leadership contributed to discipline diversity especially in small (or nascent) MTTs. A separate depiction of MTT‐KR utilization indicated that data analysis, translational technologies, and novel methods were heavily utilized by MTTs, whereas other KRs contributed significant effort to infrastructure development. We conclude that the CTSA can provide a rich  infrastructural framework and scientific environment for the development of successful MTTs. Clin Trans Sci 2013; Volume 6: 60–71
Effect of the G‐protein β3 subunit 825T allele on the change of body adiposity in obese female
Authors: Hwang I. C. , Kim K. K. , Ahn H. Y. , Suh H. S. , Oh S. W.
Published: October 2012

No clinical studies on the lipolytic effect of guanine nucleotide‐binding protein β3 subunit gene (GNB3) 825T polymorphism have been performed. This study was a subinvestigation of a 12‐week randomized controlled trial (NCT01184560) for the additive effect of orlistat on sibutramine treatment. The analysis involved 101 obese females aged 18–49 years, genotyped at the GNB3 825 locus. To exclude any influence from potential confounders, we used an analysis of covariance model. After the intervention, fat mass proportion in total weight loss was significantly lower in subjects with a T allele than in those without a T allele (p = 0.034). GNB3 825T allele was associated with blunted fat mass reduction in obese females.
Further evidence of association of theABCA4gene with cleft lip/palate
Authors: Fontoura Clarissa , Silva Renato M. , Granjeiro Jose M. , Letra Ariadne
Published: October 2012

Non‐syndromic cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex etiology. Numerous genes and environmental factors, and their interactions, are thought to play a role in the susceptibility toCL/P. A recent genome‐wide association study with several populations revealed markers in/near transcription factor vmaf musculoaponeurtoic fibrosarcoma oncogene homolog B (MAFB) andATP‐binding cassette sub‐familyAmember 4 (ABCA4) genes as new susceptibility loci forCL/P. We hypothesized that these genes could also contribute toCL/Pin aBrazilian population, and hence we evaluated if the associated single‐nucleotide polymorphisms (SNPs) inMAFB(rs13041247 and rs11696257) andABCA4(rs560426 and rs481931) were associated withCL/Pin our case–control data set. We genotyped 812 Caucasian individuals (400 cases and 412 controls) from Brazil. Allele frequencies were compared for cases and controls as well as for cleft subgroups and controls.ABCA4rs540426 showed strong associations withCL/P, unilateral and rightCL/P, and bilateralCL/P, whereas theSNPrs481931 showed borderline associations withCL/Pand bilateralCL/P. No association was found forMAFB. Our results support a potential role forABCA4in the etiology ofCL/Pin individuals from Brazil.
Penetration and biological effects of topically applied cyclosporin A nanoparticles in a human skin organ culture inflammatory model
Authors: Frušić‐Zlotkin Marina , Soroka Yoram , Tivony Ran , Larush Liraz , Verkhovsky Lilian , Brégégère François Menahem , Neuman Rami , Magdassi Shlomo , Milner Yoram
Published: October 2012

Systemic antipsoriatic therapies have potentially life‐threatening, long‐term side effects. The efficacy of topical drugs is poor, but may be improved by the use of delivery systems based on drug nanoparticles. To produce nanoparticles (NP) composed of cyclosporin A, a classical antipsoriatic drug, and to investigate their penetration and biological effects in human skin affected by psoriatic symptoms, poly‐ε‐caprolactone (PCL) and cyclosporin A (CsA) NP were prepared by the solvent evaporation method. Skin penetration was followed using fluorescently labeled NP in human skin organ cultures (hSOC). Psoriatic symptoms were mimicked in hSOC by the treatment with epidermal growth factor (EGF) and bacterial lipopolysaccharide (LPS). Cell viability in hSOC was evaluated by the resazurin test, and cytokine secretion into the growth medium was measured by immunodetection. We showed that topically applied NP diffused throughout the epidermis within two hours and through the dermis within the following day. They significantly reduced the secretion of inflammatory cytokines IL–1β, IL–6, IL–8, IL–20 and IL–23. At active doses, no cytotoxicity was detected. This type of NP display relevant properties for the use as topical anti‐inflammatory agents and may help to resorb psoriatic lesions.
Crystal structure of greglin, a novel non‐classical Kazal inhibitor, in complex with subtilisin
Authors: Derache Chrystelle , Epinette Christophe , Roussel Alain , Gabant Guillaume , Cadene Martine , Korkmaz Brice , Gauthier Francis , Kellenberger Christine
Published: October 2012

Greglin is an 83‐residue serine protease inhibitor purified from the ovaries of the locust Schistocerca gregaria. Greglin is a strong inhibitor of subtilisin and human neutrophil elastase, acting at sub‐nanomolar and nanomolar concentrations, respectively; it also inhibits neutrophil cathepsin G, α‐chymotrypsin and porcine pancreatic elastase, but to a lesser extent. In the present study, we show that greglin resists denaturation at high temperature (95 °C) and after exposure to acetonitrile and acidic or basic pH. Greglin is composed of two domains consisting of residues 1–20 and 21–83. Mass spectrometry indicates that the N‐terminal domain (1–20) is post‐translationally modified by phosphorylations at three sites and probably contains a glycosylation site. The crystal structure of the region of greglin comprising residues 21–78 in complex with subtilisin was determined at 1.75 Å resolution. Greglin represents a novel member of the non‐classical Kazal inhibitors, as it has a unique additional C‐terminal region (70–83) connected to the core of the molecule via a supplementary disulfide bond. The stability of greglin was compared with that of an ovomucoid inhibitor. The thermostability and inhibitory specificity of greglin are discussed in light of its structure. In particular, we propose that the C‐terminal region is responsible for non‐favourable interactions with the autolysis loop (140‐loop) of serine proteases of the chymotrypsin family, and thus governs specificity.

Database

The atomic coordinates and structure factors for the greglin–subtilisin complex have been deposited with the RCSB Protein Data Bank under accession number 4GI3.

Structured digital abstract

Greglin and Subtilisin Carlsberg bind by X-ray crystallography (View interaction)
Climate warming over the past three decades has shortened rice growth duration in China and cultivar shifts have further accelerated the process for late rice
Authors: Zhang Tianyi , Huang Yao , Yang Xiaoguang
Published: October 2012

An extensive dataset on rice phenology in China, including 202 series broadly covering the past three decades (1980s–2000s), was compiled. From these data, we estimated the responses of growth duration length to temperature using a regression model based on the data with and without detrending. Regression coefficients derived from the detrended data reflect only the temperature effect, whereas those derived from data without detrending represent a combined effect of temperature and confounding cultivar shifts. Results indicate that the regression coefficients calculated from the data with and without detrending show an average shortening of the growth duration of 4.1–4.4 days for each additional increase in temperature over the full growth cycle. Using the detrended data, 95.0% of the data series exhibited a negative correlation between the growth duration length and temperature; this correlation was significant in 61.9% of all of the data series. We then compared the difference between the two regression coefficients calculated from data with and without detrending and found a significantly greater temperature sensitivity using the data without detrending (−2.9 days °C−1) than that derived from the detrended data (−2.0 days °C−1) in the period of emergence to heading for the late rice, producing a negative difference in temperature sensitivity (−0.9 days °C−1). This implies that short‐duration cultivars were planted with increase in temperature and exacerbated the undesired phenological change. In contrast, positive differences were detected for the single (0.6 days °C−1) and early rice (0.5 days °C−1) over the full growth cycle, which might indicate that long‐duration cultivars were favoured with climate warming, but these differences were insignificant. In summary, our results suggest that a major, temperature induced change in the rice growth duration is underway in China and that using a short‐duration cultivar has been accelerating the process for late rice.
Soybean extract showed modulation of retinoic acid‐related gene expression of skin and photo‐protective effects in keratinocytes
Authors: Park N.‐H. , Park J.‐S. , Kang Y.‐G. , Bae J.‐H. , Lee H.‐K. , Yeom M.‐H. , Cho J.‐C. , Na Y. J.
Published: October 2012

Synopsis

Soy extracts are well known as medicinal and nutritional ingredients, and exhibit benefits towards human skin including depigmenting or anti‐ageing effects. Despite the wrinkle decreasing effects of retinoids on skin as an anti‐ageing ingredient, retinoid application can causes photo‐sensitive responses such as skin irritation. Thus, their daytime usage is not recommended. The aim of this study is the investigation into the activities of soybean extract as an anti‐ageing ingredient and their comparison to retinoids in this respect. Soybean extract decreased the relative ratio of MMP‐1/TIMP‐1 mRNA to the same degree as retinoic acid in normal human fibroblasts. It also affected mRNA levels of HAS2 and CRABP2 in normal human keratinocytes. Furthermore, we investigated its effect on mRNA expression of histidase, an enzyme that converts histidine into urocanic acid, the main UV light absorption factor of the stratum corneum. Unlike the complete inhibition of histidase exhibited by the mRNA expression of retinoic acid, the effect of soybean extract on histidase gene expression was weaker in normal human keratinocytes. Also, soybean extract pretreatment inhibited UVB‐induced cyclobutane pyrimidine dimer formation dose‐dependently in normal human keratinocytes. In this study, we found that soybean extract modulated retinoic acid‐related genes and showed photo‐protective effects. Our findings suggest that soybean extract could be an anti‐ageing ingredient that can be safely used under the sunlight.
Morphological characterization of solar lentigines by in vivo reflectance confocal microscopy: a longitudinal approach
Authors: Pollefliet C. , Corstjens H. , González S. , Hellemans L. , Declercq L. , Yarosh D.
Published: October 2012

Synopsis

Solar lentigines are benign hyperpigmented skin lesions. Despite their widespread distribution, knowledge on the mechanisms of development is largely unknown. A clinical study was designed in which solar lentigines were characterized using various non‐invasive clinical techniques. A subset of solar lentigines was followed over a 5‐year time period. One hundred and twenty‐eight solar lentigines were evaluated using in vivo reflectance confocal microscopy (RCM) for the evaluation of the length and density of their dermal papillae as well as the deformation of the alignment pattern of hyperrefractive basal cells. Skin colour, colour contrast, the size of the solar lentigo, epidermal proliferation rate, melanin and haemoglobin content were quantified. RCM imaging of solar lentigines revealed a profound structural deformation of the dermal papillae, as the alignment pattern of hyperrefractive basal cells shifted from a circle in non‐lesional skin to an irregular non‐circular shape in solar lentigines. There was a rise in the number of dermal papillae, and these dermal papillae were significantly longer. Solar lentigines had increased melanin and haemoglobin levels and a higher rate of epidermal proliferation. For a subset of nineteen solar lentigines, a longitudinal study was set‐up in which these measurements were repeated 5 years after the first evaluation. The deformation and the number of the hyperrefractive dermal papillary rings increased significantly over the 5‐year time span. The size of the lesion increased, and the skin colour became darker. RCM is a useful non‐invasive clinical tool for the characterization of solar lentigines, in particular the compressive deformation of the dermal papillae. This deformation became more severe over a time period of 5 years. To our knowledge, this is the first time that the in vivo time‐dependent progression of solar lentigines was supported by RCM images, contributing to an improved understanding of the formation and progression of solar lentigines.
Efficacy of a Novel Treatment Serum in the Improvement of Photodamaged Skin
Authors: Sonti S. , Makino E. T. , Garruto J. A. , Gruber J. V. , Rao S. , Mehta R. C.
Published: October 2012

Synopsis

A novel treatment serum formulated to target multiple pathways in the anti‐ageing cascade was tested both in vitro and in clinical settings. In vitro testing was performed to assess the ability to stimulate key proteins and genes fundamental to the anti‐ageing cascade. The antioxidant potential of the formulation was studied in a UV‐irradiation clinical study. A 12‐week, open‐label, single‐centre study was conducted to determine whether this uniquely formulated topical treatment serum could improve visible signs of facial photodamage. Clinical evaluations showed statistically significant reductions in fine wrinkles and coarse wrinkles and improvements in skin texture, tone and radiance starting at week 4 with continued improvements at weeks 8 and 12. Subject self‐assessments confirmed that the beneficial effects of the treatment serum were readily observed by the users. The treatment serum was well tolerated with no treatment‐related adverse events reported during the 12‐week study. Use of this novel treatment serum produced significant improvements in the visible signs of facial photodamage.
Compensatory growth in juvenile roach Rutilus caspicus: effect of starvation and re‐feeding on growth and digestive surface area
Authors: Abolfathi M. , Hajimoradloo A. , Ghorbani R. , Zamani A.
Published: October 2012

The aim of this study was to investigate compensatory growth in juvenile Rutilus caspicus during starvation and re‐feeding periods. The results confirmed the existence of compensatory growth in R. caspicus which depended on the duration of food deprivation. Complete compensatory growth occurred in the fish that were food deprived for at least 3 weeks. Starvation and re‐feeding had no significant effect on the digestive somatic index and intestinal surface areas in the fish that were food deprived for 1 week, while they showed a significant decrease and increase, during starvation and re‐feeding in the fish that were food deprived for 2 and 3 weeks. This knowledge may have application in aquaculture, as appropriate exploitation of compensatory growth can give increased growth rate and feeding efficiency.
Tissue preservation biases in stable isotopes of fishes and molluscs from Patagonian lakes
Authors: Correa C.
Published: October 2012

Field work commonly involves preserving samples for later use; however, most preservation methods distort stable‐isotope (SI) signatures that are of interest to ecologists. Although preservation of muscle samples with table salt and rubbing alcohol affected the SI (δ13C and δ15N) of important consumers in Patagonian lakes (molluscs and fishes), variation among individuals and lakes generally exceeded that among preservation treatments. Mathematical corrections for these preservation biases are provided, and a potentially bias‐free preservation by air‐drying is suggested.
Addiction Research Centres and the Nurturing of Creativity: National Drug Dependence Treatment Centre, India—a profile
Authors: Ray Rajat , Dhawan Anju , Chopra Anita
Published: October 2012

The National Drug Dependence Treatment Centre (NDDTC) is a part of the All India Institute of Medical Sciences, a premier autonomous medical university in India. This article provides an account of its origin and its contribution to the field of substance use disorder at the national and international levels. Since its establishment, the NDDTC has played a major role in the development of various replicable models of care, the training of post‐graduate students of psychiatry, research, policy development and planning. An assessment of the magnitude of drug abuse in India began in the early 1990s and this was followed by a National Survey on Extent, Patterns and Trends of Drug Abuse in 2004. Several models of clinical care have been developed for population subgroups in diverse settings. The centre played an important role in producing data and resource material which helped to scale up opioid substitution treatment in India. A nationwide database on the profile of patients seeking treatment (Drug Abuse Monitoring System) at government drug treatment centres has also been created. The centre has provided valuable inputs for the Government of India's programme planning. Besides clinical studies, research has also focused on pre‐clinical studies. Capacity‐building is an important priority, with training curricula and resource material being developed for doctors and paramedical staff. Many of these training programmes are conducted in collaboration with other institutions in the country. The NDDTC has received funding from several national and international organizations for research and scientific meetings, and, most recently (2012), it has been designated as a World Health Organization Collaborating Centre on Substance Abuse.
Overlooked and underestimated? Problematic alcohol use in clients recovering from drug dependence
Authors: Staiger Petra K. , Richardson Ben , Long Caroline M. , Carr Victoria , Marlatt G. Alan
Published: October 2012

Aims

Despite recognition of the harms related to alcohol misuse and its potential to interfere substantially with sustained recovery from drug dependency, research evaluating drug treatment outcomes has not addressed the issue comprehensively. It has been overlooked possibly because treatment research has been framed according to the primary drug of choice, rather than investigating the interactions between different combinations of drugs and/or alcohol use. This paper reports on a systematic review investigating whether concurrent alcohol use could impede recovery from illicit drug use in two potential ways: first, alcohol could become a substitute addiction and/or secondly, alcohol misuse post‐treatment may place an individual at risk for relapse to their primary drug problem.

Method

A systematic search of four relevant databases was undertaken to identify peer‐reviewed, quantitative drug treatment outcome studies that reported alcohol use pre‐, post‐treatment and follow‐up.

Results

The search revealed 567 papers, of which 13 were assessed as fulfilling the key inclusion criteria.The review indicated inconsistent and therefore inconclusive support for the substitution hypothesis. However, the data revealed consistent support for the hypothesis that alcohol use increases relapse to drug use.

Conclusions

(i) The potential negative impact of alcohol misuse on drug treatment outcomes remains under‐researched and overlooked; (ii) alcohol consumption post‐drug treatment may increase the likelihood that an individual will relapse to their primary drug; (ii) existing evidence regarding the substitution hypothesis is inconclusive, although there was an indication that a subgroup of participants will be vulnerable to alcohol becoming the primary addiction instead of drugs. We argue that future drug treatment outcome studies need to include detailed analysis of the influence of alcohol use pre‐ and post‐drug treatment.
Estimating root–soil contact from 3D X‐ray microtomographs
Authors: Schmidt S. , Bengough A. G. , Gregory P. J. , Grinev D. V. , Otten W.
Published: October 2012

Adequate contact with the soil is essential for water and nutrient adsorption by plant roots, but the determination of root–soil contact is a challenging task because it is difficult to visualize roots in situ and quantify their interactions with the soil at the scale of micrometres. A method to determine root–soil contact using X‐ray microtomography was developed. Contact areas were determined from 3D volumetric images using segmentation and iso‐surface determination tools. The accuracy of the method was tested with physical model systems of contact between two objects (phantoms). Volumes, surface areas and contact areas calculated from the measured phantoms were compared with those estimated from image analysis. The volume was accurate to within 0.3%, the surface area to within 2–4%, and the contact area to within 2.5%. Maize and lupin roots were grown in soil (<2 mm) and vermiculite at matric potentials of −0.03 and −1.6 MPa and in aggregate fractions of 4–2, 2–1, 1–0.5 and < 0.5 mm at a matric potential of −0.03 MPa. The contact of the roots with their growth medium was determined from 3D volumetric images. Macroporosity (>70 µm) of the soil sieved to different aggregate fractions was calculated from binarized data. Root‐soil contact was greater in soil than in vermiculite and increased with decreasing aggregate or particle size. The differences in root–soil contact could not be explained solely by the decrease in porosity with decreasing aggregate size but may also result from changes in particle and aggregate packing around the root.
Comparison of cyanobacterial and green algal growth rates at different temperatures
Authors: LÜRLING MIQUEL , ESHETU FASSIL , FAASSEN ELISABETH J. , KOSTEN SARIAN , HUSZAR VERA L. M.
Published: October 2012

1. The hypothesis that cyanobacteria have higher optimum growth temperatures and higher growth rates at the optimum as compared to chlorophytes was tested by running a controlled experiment with eight cyanobacteria species and eight chlorophyte species at six different temperatures (20–35 °C) and by performing a literature survey.

2. In the experiment, all organisms except the chlorophyte Monoraphidium minutum grew well up to 35 °C. The chlorophyte Chlamydomonas reinhardtii was the fastest‐growing organism over the entire temperature range (20–35 °C).

3. Mean optimum growth temperatures were similar for cyanobacteria (29.2 °C) and chlorophytes (29.2 °C). These results are concordant with published data, yielding slightly higher mean optimum growth temperatures for cyanobacteria (27.2 °C) than for chlorophytes (26.3 °C).

4. Mean growth rates of cyanobacteria at 20 °C (0.42 day−1) were significantly lower than those of chlorophytes at 20 °C (0.62 day−1). However, at all other temperatures, there were no differences between mean growth rates of cyanobacteria and chlorophytes.

5. Mean growth rates at the optimum temperature were similar for cyanobacteria (0.92 day−1) and chlorophytes (0.96 day−1). However, analysis of published data revealed that growth rates of cyanobacteria (0.65 day−1) were significantly lower than those of chlorophytes (0.93 day−1) at their optimum temperatures.

6. Although climate warming will probably lead to an intensification of cyanobacterial blooms, our results indicate that this might not be as a result of higher growth rates of cyanobacteria compared with their chlorophyte competitors. The competitive advantage of cyanobacteria can more likely be attributed to their ability to migrate vertically and prevent sedimentation in warmer and more strongly stratified waters and to their resistance to grazing, especially when warming reduces zooplankton body size.
Short‐period static correction without Normal Move Out†
Authors: Masjukov Andrey V. , Murzov Igor S.
Published: October 2012

Static correction is a common step in a seismic data proccessing flowchart for land data. Here we propose a new algorithm for automatic short‐period static correction. The algorithm is based on the assumption that seismic events after short‐period static correction should be locally plane nearly everywhere. No other assumptions are made. Therefore the proposed method does not require a preliminary velocity analysis. The algorithm consists in two main parts: evaluation of second spatial differences of trajectories and subsequent regularized integration of these differences. The proposed method proves its robustness and shows results comparable with conventional residual static correction based on improving common‐midpoint stacking. In contrast to the conventional residual static, the proposed algorithm can estimate short‐period statics in complex cases where common‐midpoint stacking fails because of non‐hyperbolic events.
REVIEW: Archive and refugia of soil organisms: applying a pedodiversity framework for the conservation of biological and non‐biological heritages
Authors: Ibáñez Juan José , Krasilnikov Pavel V. , Saldaña Asunción
Published: October 2012

The pedosphere is a part of our natural heritage. Soils should be considered both for their biological and for their geological resources.

During the Anthropocene, human activities have dramatically changed the land surface and remodified soil cover, resulting in many natural pedotaxa being at risk of extinction. Recently, biogeographers and ecologists recognized that numerous biotaxa should be considered as edaphic endemisms, and as a consequence, in situ soil preservation is important relative to both its biological and geological value.

This contribution discusses the similarity and differences between biodiversity and pedodiversity and proposes using pedodiversity as a surrogate measure of above‐ground biodiversity and an indicator of below‐ground biodiversity.

Another objective is to explore the relevance of soil diversity to soil ecology by illustrating how the analysis of pedotaxa and their genetic soil horizons can be applied in conservation biology. To preserve biological and geological heritage inherent to the pedosphere, we propose to design a network of soil reserves. The proposed network could also be an efficient way to preserve soil characteristics and qualities of undisturbed soils that would become benchmarks for soil monitoring programs.

Synthesis and applications. The coincidence between patterns of biodiversity and pedodiversity offers a new and unexplored direction for understanding the genesis of biological and non‐biological assemblages and the spatial patterns of soils and living organisms. Pedodiversity can be used as a practical surrogate indicator of soil diversity. We provide a pedodiversity framework for the design of a network of soil reserves for the preservation and monitoring of soil biodiversity. This new framework could contribute toward the development of a unified theory of natural diversity and to understanding the role of the pedosphere in the provision of ecosystem services.
Changes in the C/N balance caused by increasing external ammonium concentrations are driven by carbon and energy availabilities during ammonium nutrition in pea plants: the key roles of asparagine synthetase and anaplerotic enzymes
Authors: Ariz Idoia , Asensio Aaron C. , Zamarreño Angel M. , García‐Mina Jose M. , Aparicio‐Tejo Pedro M. , Moran Jose F.
Published: October 2012

An understanding of the mechanisms underlying ammonium (NH4+) toxicity in plants requires prior knowledge of the metabolic uses for nitrogen (N) and carbon (C). We have recently shown that pea plants grown at high NH4+ concentrations suffer an energy deficiency associated with a disruption of ionic homeostasis. Furthermore, these plants are unable to adequately regulate internal NH4+ levels and the cell‐charge balance associated with cation uptake. Herein we show a role for an extra‐C application in the regulation of C–N metabolism in NH4+‐fed plants. Thus, pea plants (Pisum sativum) were grown at a range of NH4+ concentrations as sole N source, and two light intensities were applied to vary the C supply to the plants. Control plants grown at high NH4+ concentration triggered a toxicity response with the characteristic pattern of C‐starvation conditions. This toxicity response resulted in the redistribution of N from amino acids, mostly asparagine, and lower C/N ratios. The C/N imbalance at high NH4+ concentration under control conditions induced a strong activation of root C metabolism and the upregulation of anaplerotic enzymes to provide C intermediates for the tricarboxylic acid cycle. A high light intensity partially reverted these C‐starvation symptoms by providing higher C availability to the plants. The extra‐C contributed to a lower C4/C5 amino acid ratio while maintaining the relative contents of some minor amino acids involved in key pathways regulating the C/N status of the plants unchanged. C availability can therefore be considered to be a determinant factor in the tolerance/sensitivity mechanisms to NH4+ nutrition in plants.
The incidence of delirium in Norwegian intensive care units; deep sedation makes assessment difficult
Authors: WØIEN H. , BALSLIEMKE S. , STUBHAUG A.
Published: October 2012

Background

Delirium in critically ill patients is associated with increased length of hospital stay, mortality and costs, and may lead to long‐term cognitive impairment. It is often overlooked by clinicians if structured observation is not performed routinely. A national Norwegian survey reported that systematic screening and assessment of delirium were never or seldom performed. The purpose of this study was to test the usefulness of the Confusion Assessment Method for the Intensive Care Unit (CAM‐ICU) and to describe the incidence of delirium in critically ill patients at two Norwegian hospitals.

Methods

We conducted a two‐site, prospective, descriptive study including patients between 18 and 80 years, intubated or mask ventilated at admission, with an ICU stay > 48 h. The CAM‐ICU was scored three times daily. In addition, illness severity, sedation level, pain assessment, drug use and other treatment factors were systematically assessed.

Results

Total ICU stays of 139 patients were studied and covered 958 patient days. The incidence of delirium was 23%. Thirty per cent of the patients representing 407 patient days were unable to be assessed at any assessment, mainly due to deep sedation. The patients were delirium and coma free in 45.9% of total days.

Conclusion

Of the patients, 23% were classed as delirious (CAM‐ICU positive) at least once during their stay. The CAM‐ICU was difficult to use in patients with sedation so deep that they hardly gave eye contact and responded only weakly to verbal stimulation. Focusing on less sedation and further modifications to the CAM‐ICU may benefit ICU patients in the future.
Study of gastro‐oesophageal reflux disease in patients with mild‐to‐moderate chronic obstructive pulmonary disease in India
Authors: KAMBLE NITISH L. , KHAN NAUSHAD A. , KUMAR NARESH , NAYAK HEMANTA K. , DAGA MRADUL K.
Published: October 2012

Background and objective:  To study the incidence and pattern of gastro‐oesophageal reflux disease (GORD) in patients with mild‐to‐moderate chronic obstructive pulmonary disease (COPD) using dual‐probe 24‐h oesophageal pH recording.

Methods:  This was a prospective study of 50 patients with mild‐to‐moderate stage COPD based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. A detailed history of illness along with spirometry was done in all patients. In the study group, reflux symptoms were measured using a validated scoring system. All the patients underwent oesophageal manometry and dual‐probe 24‐h oesophageal pH recording.

Results:  Symptoms of gastro‐oesophageal reflux were present in 38 patients. Twenty‐four‐hour oesophageal pH monitoring revealed pathological reflux in 31 out of 38 symptomatic and 8 out of 12 asymptomatic patients. The overall rate of GORD was 78% in our study. Only distal GORD was observed in 11 (28.9%), and both distal and proximal GORD was observed in 20 (52.6%) out of the 38 symptomatic subjects. In the remaining 12 asymptomatic patients, eight had GORD. Distal GORD was present in six (50%) patients, and two (16.6%) had both distal and proximal GORD in this group. Isolated proximal GORD was not observed in any patient.

Conclusions:  There is an increased occurrence of GORD in patients with even mild‐to‐moderate COPD.