bluuebunny/crossref_metadata_2025 huggingface dataset:
An IL6-correlated signature in serous epithelial ovarian cancer associates with growth factor response
Authors: Pinciroli Patrizia , Alberti Chiara , Sensi Marialuisa , Canevari Silvana , Tomassetti Antonella
Published: July 2013

Background

Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers; the majority of EOC is the serous histotype and diagnosed at advanced stage. IL6 is the cytokine that has been found most frequently associated with carcinogenesis and progression of serous EOCs. IL6 is a growth-promoting and anti-apoptotic factor, and high plasma levels of IL6 in advanced stage EOCs correlate with poor prognosis. The objective of the present study was to identify IL6 co-regulated genes and gene network/s in EOCs.

Results

We applied bioinformatics tools on 7 publicly available data sets containing the gene expression profiles of 1262 EOC samples. By Pearson's correlation analysis we identified, in EOCs, an IL6-correlated gene signature containing 40 genes mainly associated with proliferation. 33 of 40 genes were also significantly correlated in low malignant potential (LMP) EOCs, while 7 genes, named C5AR1, FPR1, G0S2, IL8, KLF2, MMP19, and THBD were IL6-correlated only in advanced stage EOCs. Among the 40-gene signature EGFR ligand HBEGF, genes of the EGR family members and genes encoding for negative feedback regulators of growth factor signaling were included. The results obtained by Gene Set Enrichment and Ingenuity Pathway Analyses enabled the identification, respectively, of gene sets associated with ‘early growth factor response’ for the 40-gene signature, and a biological network related to ‘thrombosis and cardiovascular disease’ for the 7-gene signature. In agreement with these results, selected genes from the identified signatures were validated in vitro by real time RT-PCR in serous EOC cell lines upon stimulation with EGF.

Conclusions

Serous EOCs, independently of their aggressiveness, co-regulate IL6 expression together with that of genes associated to growth factor signaling, arguing for the hypothesis that common mechanism/s driven by EGFR ligands characterize both advanced-stage and LMP EOCs. Only advanced-stage EOCs appeared to be characterized by a scenario that involves genes which are so far associated with thrombosis and cardiovascular disease, thus suggesting that this pathway is implicated in the growth and/or spread of more aggressive tumors. We have discovered novel activated signaling pathways that drive the expression of IL6 and of co-regulated genes and are possibly involved in the pathobiology of EOCs.
APOBEC3 inhibits DEAD-END function to regulate microRNA activity
Authors: Ali Sara , Karki Namrata , Bhattacharya Chitralekha , Zhu Rui , MacDuff Donna A , Stenglein Mark D , Schumacher April J , Demorest Zachary L , Harris Reuben S , Matin Angabin , Aggarwal Sita
Published: July 2013

The RNA binding protein DEAD-END (DND1) is one of the few proteins known to regulate microRNA (miRNA) activity at the level of miRNA-mRNA interaction. DND1 blocks miRNA interaction with the 3′-untranslated region (3′-UTR) of specific mRNAs and restores protein expression. Previously, we showed that the DNA cytosine deaminase, APOBEC3 (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide like 3), interacts with DND1. APOBEC3 has been primarily studied for its role in restricting and inactivating retroviruses and retroelements. In this report, we examine the significance of DND1-APOBEC3 interaction. We found that while human DND1 inhibits miRNA-mediated inhibition of P27, human APOBEC3G is able to counteract this repression and restore miRNA activity. APOBEC3G, by itself, does not affect the 3′-UTR of P27. We found that APOBEC3G also blocks DND1 function to restore miR-372 and miR-206 inhibition through the 3′-UTRs of LATS2 and CX43, respectively. In corollary experiments, we tested whether DND1 affects the viral restriction function or mutator activity of APOBEC3. We found that DND1 does not affect APOBEC3 inhibition of infectivity of exogenous retrovirus HIV (ΔVif) or retrotransposition of MusD. In addition, examination of Ter/Ter;Apobec3−/− mice, lead us to conclude that DND1 does not regulate the mutator activity of APOBEC3 in germ cells. In summary, our results show that APOBEC3 is able to modulate DND1 function to regulate miRNA mediated translational regulation in cells but DND1 does not affect known APOBEC3 function.
Osteitis in the dens of axis caused by Treponema pallidum
Authors: Fabricius Thilde , Winther Charlotte , Ewertsen Caroline , Kemp Michael , Nielsen Susanne Dam
Published: July 2013

Background

Syphilis has been referred to as “the great imitator” due to its ability to imitate other diseases. Untreated syphilis becomes a systemic infection that can involve almost every organ systems. Treponema pallidum has a high affinity for bone tissue, but osteitis has mainly been described in late stages of the disease. Vertebral involvement is rare, and this is to our knowledge the first case describing syphilitic spondylitis in early acquired syphilis.

Case presentation

We here describe destructive osteitis in the vertebral column as the initial manifestation of early acquired syphilis in a 24-year-old caucasian homosexual male with HIV infection. The diagnosis was reached by universal bacterial PCR and DNA sequencing of the DNA product. It was confirmed by PCR specific for Treponema pallidum, immunohistochemistry and detection of increasing antibody titer.

Conclusions

As syphilis has re-emerged in Western countries and remains a worldwide common disease it is important to have in mind as a causative agent of skeletal symptoms, especially among HIV-infected individuals or men who have sex with men (MSM).
Identification of an endo-1,4-beta-xylanase of Ustilago maydis
Authors: Geiser Elena , Wierckx Nick , Zimmermann Martin , Blank Lars M
Published: July 2013

Background

The utilization of raw biomass components such as cellulose or hemicellulose for the production of valuable chemicals has attracted considerable research interest in recent years. One promising approach is the application of microorganisms that naturally convert biomass constituents into value added chemicals. One of these organisms – Ustilago maydis – can grow on xylan, the second most abundant polysaccharide in nature, while at the same time it produces chemicals of biotechnological interest.

Results

In this study, we present the identification of an endo-1,4-beta xylanase responsible for xylan degradation. Xylanase activity of U. maydis cells was indirectly detected by the quantification of released reducing sugars and could be confirmed by visualizing oligosaccharides as degradation products of xylan by thin layer chromatography. A putative endo-1,4-beta-xylanase, encoded by um06350.1, was identified in the supernatant of xylan-grown cells. To confirm the activity, we displayed the putative xylanase on the surface of the xylanase negative Saccharomyces cerevisiae EBY100. The presented enzyme converted xylan to xylotriose, similar to the source organism U. maydis.

Conclusions

The xylan degradation ability together with its unicellular and yeast-like growth makes U. maydis MB215 a promising candidate for the production of valuable chemicals such as itaconic acid or glycolipids from lignocellulosic biomass. Therefore, the characterization of the endo-1,4-beta-xylanase, encoded by um06350.1, is a further step towards the biotechnological application of U. maydis and its enzymes.
Cesarean section and increased body mass index in school children: two cohort studies from distinct socioeconomic background areas in Brazil
Authors: Goldani Marcelo Zubaran , Barbieri Marco Antonio , da Silva Antônio Augusto Moura , Gutierrez Manoel Romeu Pereira , Bettiol Heloisa , Goldani Helena Ayako Sueno
Published: July 2013

Background

Recent studies have raised controversy regarding the association between cesarean section and later obesity in the offspring. The purpose of this study was to assess the association of cesarean section with increased body mass index (BMI) and obesity in school children from two Brazilian cities with distinct socioeconomic backgrounds.

Methods

Two birth cohorts respectively born in 1994 in Ribeirao Preto, a wealthy city in Southeast, and in 1997/98 in Sao Luis, a less wealthy city in Northeast of Brasil, were evaluated. After birth, 2,846 pairs of mothers-newborns were evaluated in Ribeirao Preto and 2,542 in Sao Luis. In 2004/05, 790 children aged 10/11 years were randomly reassessed in Ribeirao Preto and 673 at 7/9 years in Sao Luis. Information on type of delivery, maternal and child characteristics, socioeconomic position and anthropometric measurements were collected after birth and at school age. Obesity was defined as BMI ≥ 95th percentile at school age.

Results

Obesity rate was 13.0% in Ribeirao Preto and 2.1% in Sao Luis. Cesarean section was associated with obesity and remained significant after adjustment only in Ribeirao Preto [OR = 1.74 (95% CI: 1.04; 2.92)]. The association between cesarean section and BMI remained significant after adjustment for maternal schooling, maternal smoking during pregnancy, duration of breastfeeding, gender, birth weight and gestational age, type of school and, only in Sao Luis, pre-pregnancy maternal weight. In Ribeirao Preto children born by cesarean section had BMI 0.31 kg/m2 (95%CI: 0.11; 0.51) higher than those born by vaginal delivery. In Sao Luis BMI of children born by cesarean section was 0.28 kg/m2 higher (95%CI: 0.08; 0.49) than those born by vaginal delivery.

Conclusion

A positive association between cesarean section and increased BMI z-score was demonstrated in areas with different socioeconomic status in a middle-income Country.
Adenoma malignum of the uterine cervix: report of four cases
Authors: Ki Eun Young , Byun Seung Won , Park Jong Sup , Lee Sung Jong , Hur Soo Young
Published: July 2013

Adenoma malignum (AM) of the cervix is a rare disease and it is difficult to diagnose due to the deceptively benign appearance of the tumor cells. These lesions have mucin-rich cystic lesions and are usually situated deep in the cervix. Since AM is very rare, standard screening tests, diagnostic tools and treatments have not yet been established. Radiologically, it mimics multiple nabothian cysts as a benign-looking tumor. Histologically, AM is a well-differentiated adenocarcinoma and could be misdiagnosed as a benign lesion. These findings make a preoperative diagnosis of AM difficult and can result in surgery being performed based on a misdiagnosis. We report here on four cases of pathologically confirmed AM.
Low-dose monobutyl phthalate stimulates steroidogenesis through steroidogenic acute regulatory protein regulated by SF-1, GATA-4 and C/EBP-beta in mouse Leydig tumor cells
Authors: Hu Yanhui , Dong Congcong , Chen Minjian , Lu Jing , Han Xiumei , Qiu Lianglin , Chen Yansu , Qin Jingjing , Li Xiaocheng , Gu Aihua , Xia Yankai , Sun Hong , Li Zhong , Wang Yubang
Published: July 2013

Background

The ubiquitous use of dibutyl phthalate (DBP), one of the most widely used plasticizers, results in extensive exposure to humans and the environment. DBP and its major metabolite, monobutyl phthalate (MBP), may alter steroid biosynthesis and their exposure may lead to damage to male reproductive function. Low-doses of DBP/MBP may result in increased steroidogenesis in vitro and in vivo. However, the mechanisms of possible effects of low-dose MBP on steroidogenesis remain unclear. The aim of present study was to elaborate the role of transcription factors and steroidogenic acute regulatory protein in low-dose MBP-induced distruption of steroidogenesis in mouse Leydig tumor cells (MLTC-1 cells).

Methods

In the present study, MLTC-1 cells were cultured in RPMI 1640 medium supplemented with 2 g/L sodium bicarbonate. Progesterone level was examined by I125-pregesterone Coat-A-Count radioimmunoassay (RIA) kits. mRNA and protein levels were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. DNA-binding of several transcription factors was examined by electrophoretic mobility shift assay (EMSA).

Results

In this study, various doses of MBP (0, 10(−9), 10(−8), 10(−7), or 10(−6) M) were added to the medium followed by stimulation of MLTC-1 cells with human chorionic gonadotrophin (hCG). The results showed that MBP increased progesterone production and steroidogenic acute regulatory protein (StAR) mRNA and protein levels. However, the protein levels of cytochrome P450scc and 3 beta-hydroxy-steroid dehydrogenase (3 beta-HSD) were unchanged after MBP treatment. EMSA assay showed that DNA-binding of steroidogenic factors 1(SF-1), GATA-4 and CCAAT/enhancer binding protein-beta (C/EBP-beta) was increased in a dose-dependent manner after MBP exposure. Western blot tests were next employed and confirmed that the protein levels of SF-1, GATA-4 and C/EBP-beta were also increased. Additionally, western blot tests confirmed the expression of DAX-1, negative factor of SF-1, was dose-dependently down regulated after MBP exposure, which further confirmed the role of SF-1 in MBP-stimulated steroid biosynthesis.

Conclusions

In conclusion, we firstly delineated the regulation of StAR by transcription factors including SF-1, GATA-4 and C/EBP-beta maybe critical mechanism involved in low-dose MBP-stimulated steroidogenesis.
Targeting density-enhanced phosphatase-1 (DEP-1) with antisense oligonucleotides improves the metabolic phenotype in high-fat diet-fed mice
Authors: Krüger Janine , Trappiel Manuela , Dagnell Markus , Stawowy Philipp , Meyborg Heike , Böhm Christian , Bhanot Sanjay , Östman Arne , Kintscher Ulrich , Kappert Kai
Published: July 2013

Background

Insulin signaling is tightly controlled by tyrosine dephosphorylation of the insulin receptor through protein-tyrosine-phosphatases (PTPs). DEP-1 is a PTP dephosphorylating tyrosine residues in a variety of receptor tyrosine kinases. Here, we analyzed whether DEP-1 activity is differentially regulated in liver, skeletal muscle and adipose tissue under high-fat diet (HFD), examined the role of DEP-1 in insulin resistance in vivo, and its function in insulin signaling.

Results

Mice were fed an HFD for 10 weeks to induce obesity-associated insulin resistance. Thereafter, HFD mice were subjected to systemic administration of specific antisense oligonucleotides (ASOs), highly accumulating in hepatic tissue, against DEP-1 or control ASOs. Targeting DEP-1 led to improvement of insulin sensitivity, reduced basal glucose level, and significant reduction of body weight. This was accompanied by lower insulin and leptin serum levels. Suppression of DEP-1 in vivo also induced hyperphosphorylation in the insulin signaling cascade of the liver. Moreover, DEP-1 physically associated with the insulin receptor in situ, and recombinant DEP-1 dephosphorylated the insulin receptor in vitro.

Conclusions

These results indicate that DEP-1 acts as an endogenous antagonist of the insulin receptor, and downregulation of DEP-1 results in an improvement of insulin sensitivity. DEP-1 may therefore represent a novel target for attenuation of metabolic diseases.
Logarithmic density and logarithmic statistical convergence
Authors: Alghamdi Mohammed A , Mursaleen Momammad , Alotaibi Abdullah
Published: July 2013

In this paper we use the idea of logarithmic density to define the concept of logarithmic statistical convergence. We find the relations of logarithmic statistical convergence with statistical convergence, statistical summability

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introduced by Móricz (Analysis 24:127-145, 2004) and

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MSC:40A05, 40A30.
Blow-up criteria for 3D nematic liquid crystal models in a bounded domain
Authors: Fan Jishan , Nakamura Gen , Zhou Yong
Published: July 2013

In this paper we prove some blow-up criteria for two 3D density-dependent nematic liquid crystal models in a bounded domain.

MSC:35Q30, 76D03, 76D09.
Risk factors of chronic hepatitis in antiretroviral-treated HIV infection, without hepatitis B or C viral infection
Authors: Chalermchai Thep , Hiransuthikul Narin , Tangkijvanich Pisit , Pinyakorn Suteeraporn , Avihingsanon Anchalee , Ananworanich Jintanat
Published: July 2013

Background

Increasing rates of non-AIDS defining illnesses, and in particular liver diseases, have been found after the initiation of highly active antiretroviral therapy. However, there is little evidence concerning the risk factors for and clinical characteristics of liver disease in antiretroviral (ARV)-treated HIV infection, in the absence of hepatitis B or C viral co-infection.

Methods

A nested case–control study of HIV infected volunteers, matched by starting date of anti-retroviral treatment, was conducted in a Thai cohort studied from Nov 2002 - July 2012. Cases were defined as those subjects with an elevated alanine aminotransferase (ALT ≥ 40 IU/L) at two consecutive visits six months apart, while controls were defined as individuals who never demonstrated two consecutive elevated ALT results and had a normal ALT result (< 40 IU/L) at their last visit. Both groups had normal ALT levels prior to ARV initiation. Clinical demographics and risk factors for chronic hepatitis including HIV-related illness, ARV treatment and metabolic diseases were collected and analyzed. Conditional logistic regression was used to determine risk factors for chronic hepatitis in HIV infection.

Results

A total of 124 matched pairs with HIV infection were followed over 3,195 person-years. The mean age (±SD) was 33.0 ± 7.3 years, with 41.1% of subjects being male. The incidence of chronic hepatitis was 5.4 per 100 person-years. The median time from initiation of ARV to chronic hepatitis was 1.3 years (IQR, 0.5-3.5). From univariate analysis; male sex, plasma HIV-1 RNA level > 5 log 10 copies/ml, metabolic syndrome at baseline visit, high BMI > 23 kg/m2, abnormal HDL cholesterol at time of ALT elevation and treatment experience with NNRTI plus boosted PI were selected (p value < 0.2) to the final model of multivariate analysis. Male sex had 3.1 times greater risk of chronic hepatitis than the females by multivariate analysis (adjusted OR, 95% CI: 3.1, 1.5-6.3, p =0.002). High BMI ≥ 23 kg/m2 was also associated with 2.4 times greater risk of chronic hepatitis (adjusted OR, 95% CI: 2.4, 1.2-4.8, p = 0.01).

Conclusions

Chronic hepatitis in ARV-treated HIV-infected patients is common and may lead to a major health care problem. Male sex and high BMI ≥ 23 kg/m2 carry higher risks for developing chronic hepatitis in this study. Therefore, these patients should be closely monitored for long-term hepatotoxicity.
Protocol: Optimised methodology for isolation of nuclei from leaves of species in the Solanaceae and Rosaceae families
Authors: Sikorskaite Sidona , Rajamäki Minna-Liisa , Baniulis Danas , Stanys Vidmantas , Valkonen Jari PT
Published: July 2013

In this study, a protocol is described for rapid preparation of an enriched, reasonably pure fraction of nuclear proteins from the leaves of tobacco (Nicotiana tabacum), potato (Solanum tuberosum) and apple (Malus domestica). The protocol gives reproducible results and can be carried out quickly in 2 hours. Tissue extracts clarified with filtration were treated with non-ionic detergent (Triton X-100) to lyse membranes of contaminating organelles. Nuclei were collected from a 60% Percoll layer of density gradient following low-speed centrifugation. Western blot analysis using antibodies to marker proteins of organelles indicated that the nuclear protein fractions were highly enriched and free or nearly free of proteins from the endoplasmic reticulum and chloroplasts.
A 2-year-old girl with co-inherited cystic fibrosis and sickle cell-β+ thalassemia presenting with recurrent vaso-occlusive events during cystic fibrosis pulmonary exacerbations: a case report
Authors: Sobush Kurtis T , Thornburg Courtney D , Voynow Judith A , Davis Stephanie D , Peterson-Carmichael Stacey L
Published: July 2013

Introduction

This is the first published report of a young girl with co-inherited sickle cell-β+ thalassemia and cystic fibrosis. Although a small subset of patients with co-inherited cystic fibrosis and other hemoglobinopathies have been reported, this patient developed early hematologic and pulmonary complications that were more severe than the previous cases. To assess pulmonary co-morbidities, we used infant pulmonary function testing through the raised volume rapid thoracoabdominal compression technique as both an established study of early cystic fibrosis and also as a newer study of mechanism for early sickle cell lung disease. This further serves as the first report of the raised volume rapid thoracoabdominal compression technique to determine raised volume forced expiratory flows and fractional lung volumes in a patient with a hemoglobinopathy.

Case presentation

A 2-year-old African-American girl with co-inherited cystic fibrosis and sickle cell-β+ thalassemia developed severe hematologic complications (recurrent vaso-occlusive events, hepatic sequestration, and acute chest syndrome) during periods of cystic fibrosis pulmonary exacerbations and weight loss. Because cystic fibrosis and sickle cell-β+ thalassemia both confer distinct patterns of pulmonary disease, infant pulmonary function testing with the raised volume rapid thoracoabdominal compression technique was used to define respiratory pathophysiology and guide treatment options. Infant pulmonary function testing data demonstrated moderate-to-severe lower airways obstruction, moderate air trapping, and no evidence of restrictive lung disease.

Conclusions

Infant pulmonary function testing with the raised volume rapid thoracoabdominal compression technique guided therapy in this patient with cystic fibrosis and sickle cell-β+ thalassemia. Although this is an original case report on a unique patient, this case highlights the need to evaluate early respiratory pathophysiology in a broader population of young patients with hemoglobinopathies and screen those at risk for early pulmonary co-morbidities.
Detection and molecular typing of Leishmania tropica from Phlebotomus sergenti and lesions of cutaneous leishmaniasis in an emerging focus of Morocco
Authors: Ajaoud Malika , Es-sette Nargys , Hamdi Salsabil , El-Idrissi Abderahmane Laamrani , Riyad Myriam , Lemrani Meryem
Published: July 2013

Background

Cutaneous leishmaniasis is an infectious disease caused by flagellate protozoa of the genus Leishmania. In Morocco, anthroponotic cutaneous leishmaniasis due to Leishmania tropica is considered as a public health problem, but its epidemiology has not been fully elucidated. The main objective of this study was to detect Leishmania infection in the vector, Phlebotomus sergenti and in human skin samples, in the El Hanchane locality, an emerging focus of cutaneous leishmaniasis in central Morocco.

Methods

A total of 643 sand flies were collected using CDC miniature light traps and identified morphologically. Leishmania species were characterized by ITS1 PCR-RFLP and ITS1-5.8S rRNA gene nested-PCR of samples from 123 females of Phlebotomus sergenti and 7 cutaneous leishmaniasis patients.

Results

The sand flies collected consisted of 9 species, 7 of which belonged to the genus Phlebotomus and two to the genus Sergentomyia. Phlebotomus sergenti was the most predominant (76.67%).

By ITS1 PCR-RFLP Leishmania tropica was found in three Phlebotomus sergenti females and four patients (4/7). Using nested PCR Leishmania tropica was identified in the same three Phlebotomus sergenti females and all the 7 patients. The sequencing of the nested PCR products recognized 7 haplotypes, of which 6 have never been described.

Conclusions

This is the first molecular detection and identification of Leishmania tropica in human skin samples and Phlebotomus sergenti in support of its vector status in El Hanchane. The finding of seven Leishmania tropica haplotypes underscores heterogeneity of this species at a high level in Morocco.
Anti-inflammatory effects of apo-9′-fucoxanthinone from the brown alga, Sargassum muticum
Authors: Yang Eun-Jin , Ham Young Min , Lee Wook Jae , Lee Nam Ho , Hyun Chang-Gu
Published: July 2013

Background

The marine environment is a unique source of bioactive natural products, of which Sargassum muticum (Yendo) Fensholt is an important brown algae distributed in Jeju Island, Korea. S. muticum is a traditional Korean food stuff and has pharmacological functions including anti-inflammatory effects. However, the active ingredients from S. muticum have not been characterized.

Methods

Bioguided fractionation of the ethanolic extract of S. muticum, collected from Jeju island, led to the isolation of a norisoprenoid. Its structure was determined by analysis of the spectroscopic data. In vitro anti-inflammatory activity and mechanisms of action of this compound were examined using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells through ELISA assays and Western blot analysis.

Results

Apo-9′-fucoxanthinone, belonging to the norisoprenoid family were identified. Apo-9′-fucoxanthinone effectively suppressed LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production. This compound also exerted their anti-inflammatory actions by down-regulating of NF-κB activation via suppression of IκB-α in macrophages.

Conclusions

This is the first report describing effective anti-inflammatory activity for apo-9’-fucoxanthinone′-fucoxanthnone isolated from S. muticum. Apo-9′-fucoxanthinone may be a good candidate for delaying the progression of human inflammatory diseases and warrants further studies.
Preparation and study of vitamin A palmitate microemulsion drug delivery system and investigation of co-surfactant effect
Authors: Maleki Dizaj Solmaz
Published: July 2013

The oral route is the main route of drug delivery in many diseases. A major problem in oral oil-soluble drug administration is poor aqueous solubility. One way to deliver oil-soluble drugs is to incorporate the drug into an inert vehicle, such as microemulsions. The purpose of this research was to develop the oil-in-water (o/w) microemulsion areas of pseudo-ternary phase diagrams for a drug delivery system. Our systems consist of sunflower oil + surfactant (Tween 80) + vitamin A palmitate + different co-surfactants + water. Vitamin A palmitate is an oil-soluble drug with poor aqueous solubility. Our goal is to increase its aqueous solubility. The effects of different co-surfactants on the o/w microemulsion region were investigated. The co-surfactants studied were anhydrous glycerol, sucrose, ethanol, and 1-propranol. A titration technique was employed for the preparation of the samples. The phases were identified by visual inspection and polarized microscopy. Samples of the microemulsion area were separated, and pseudo-ternary phase diagram was plotted for them. The system sunflower oil + Tween 80 + sucrose + water+ model drug showed the largest o/w microemulsion region. Consequently, sucrose was selected as the best co-surfactant. Finally, some samples of this system were selected for particle size measurement and stability testing. Results showed that more than 90% of the samples in different temperatures (4°C, 45°C, and room temperature) are stable.
Skeletal and dental effects produced by functional regulator-2 in pre-pubertal class II patients: a controlled study
Authors: Perillo Letizia , Femiano Alberta , Palumbo Stefano , Contardo Luca , Perinetti Giuseppe
Published: July 2013

Background

Whether skeletal effects are obtained by functional appliances in class II subjects is still controversial. In this regard, most of the available studies did not clearly identify the growth phases (i.e. pubertal or not) of the treated patients. This retrospective controlled study aimed at evaluating the skeletal and dental changes in class II subjects produced by the functional regulator (FR)-2 treatment during the pre-pubertal growth phase.

Methods

The data were derived from records obtained at a university dental clinic. A total of 17 treated subjects and a total of 17 untreated controls, all pre-pubertal, matched for malocclusion, age (8.8 ± 1.5 years) and sex (18 females, 16 males), were included. The overall observational period was 1.6 ± 0.8 years for both groups.

Results

Only minor skeletal changes with very little clinical relevance were seen after the observational period. Most of the changes produced by the FR-2 treatment were at the dental level including palatal tipping of the maxillary incisors and slight proclination of the mandibular incisors, both accounting for the noteworthy overjet reduction.

Conclusions

The present study has shown that functional treatment of class II malocclusion by FR-2 appliance during the pre-pubertal growth phase is limited to modification at the dental level.
Re-evaluating currently available data and suggestions for planning randomised controlled studies regarding the use of hydroxyethyl starch in critically ill patients - a multidisciplinary statement
Authors: Meybohm Patrick , Aken Hugo Van , Gasperi Andrea De , Hert Stefan De , Rocca Giorgio Della , Girbes Armand RJ , Gombotz Hans , Guidet Bertrand , Hasibeder Walter , Hollmann Markus W , Ince Can , Jacob Matthias , Kranke Peter , Kozek-Langenecker Sibylle , Loer Stephan Alexander , Martin Claude , Siegemund Martin , Wunder Christian , Zacharowski Kai
Published: July 2013

Introduction

Hydroxyethyl starch (HES) is a commonly used colloid in critically ill patients. However, its safety has been questioned in recent studies and meta-analyses.

Methods

We re-evaluated prospective randomised controlled trials (RCT) from four meta-analyses published in 2013 that compared the effect of HES with crystalloids in critically ill patients, focusing on the adherence to 'presumably correct indication'. Regarding the definition of 'presumably correct indication', studies were checked for the following six criteria (maximum six points): short time interval from shock to randomisation (<6 h), restricted use for initial volume resuscitation, use of any consistent algorithm for haemodynamic stabilisation, reproducible indicators of hypovolaemia, maximum dose of HES, and exclusion of patients with pre-existing renal failure or renal replacement therapy.

Results

Duration of fluid administration ranged from 90 min up to a maximum of 90 days. Four studies considered follow-up until 90-day mortality, three studies 28-/30-day mortality, whereas four studies reported only early mortality. Included studies showed a large heterogeneity of the indication score ranging between 1 and 4 points with a median (25%; 75% quartile) of 4 (2; 4).

Conclusions

The most important question, whether or not HES may be harmful when it is limited to immediate haemodynamic stabilisation, cannot be answered yet in the absence of any study sufficiently addressing this question. In order to overcome the limitations of most of the previous studies, we now suggest an algorithm emphasising the strict indication of HES. Additionally, we give a list of suggestions that should be adequately considered in any prospective RCT in the field of acute volume resuscitation in critically ill patients.
Continuous positive airway pressure titration in infants with severe upper airway obstruction or bronchopulmonary dysplasia
Authors: Khirani Sonia , Ramirez Adriana , Aloui Sabrina , Leboulanger Nicolas , Picard Arnaud , Fauroux Brigitte
Published: July 2013

Abstracta

Introduction

Noninvasive continuous positive airway pressure (CPAP) is recognized as an effective treatment for severe airway obstruction in young children. The aim of the present study was to compare a clinical setting with a physiological setting of noninvasive CPAP in infants with nocturnal alveolar hypoventilation due to severe upper airway obstruction (UAO) or bronchopulmonary dysplasia (BPD).

Methods

The breathing pattern and respiratory muscle output of all consecutive infants due to start CPAP in our noninvasive ventilation unit were retrospectively analysed. CPAP set on clinical noninvasive parameters (clinical CPAP) was compared to CPAP set on the normalization or the maximal reduction of the oesophageal pressure (Poes) and transdiaphragmatic pressure (Pdi) swings (physiological CPAP). Expiratory gastric pressure (Pgas) swing was measured.

Results

The data of 12 infants (mean age 10 ± 8 mo) with UAO (n = 7) or BPD (n = 5) were gathered. The mean clinical CPAP (8 ± 2 cmH2O) was associated with a significant decrease in Poes and Pdi swings. Indeed, Poes swing decreased from 31 ± 15 cmH2O during spontaneous breathing to 21 ± 10 cmH2O during CPAP (P < 0.05). The mean physiological CPAP level was 2 ± 2 cmH2O higher than the mean clinical CPAP level and was associated with a significantly greater improvement in all indices of respiratory effort (Poes swing 11 ± 5 cm H2O; P < 0.05 compared to clinical CPAP). Expiratory abdominal activity was present during the clinical CPAP and decreased during physiological CPAP.

Conclusions

A physiological setting of noninvasive CPAP, based on the recording of Poes and Pgas, is superior to a clinical setting, based on clinical noninvasive parameters. Expiratory abdominal activity was present during spontaneous breathing and decreased in the physiological CPAP setting.
The genome and transcriptome of the enteric parasite Entamoeba invadens, a model for encystation
Authors: Ehrenkaufer Gretchen M , Weedall Gareth D , Williams Daryl , Lorenzi Hernan A , Caler Elisabet , Hall Neil , Singh Upinder
Published: July 2013

Background

Several eukaryotic parasites form cysts that transmit infection. The process is found in diverse organisms such as Toxoplasma, Giardia, and nematodes. In Entamoeba histolytica this process cannot be induced in vitro, making it difficult to study. In Entamoeba invadens, stage conversion can be induced, but its utility as a model system to study developmental biology has been limited by a lack of genomic resources. We carried out genome and transcriptome sequencing of E. invadens to identify molecular processes involved in stage conversion.

Results

We report the sequencing and assembly of the E. invadens genome and use whole transcriptome sequencing to characterize changes in gene expression during encystation and excystation. The E. invadens genome is larger than that of E. histolytica, apparently largely due to expansion of intergenic regions; overall gene number and the machinery for gene regulation are conserved between the species. Over half the genes are regulated during the switch between morphological forms and a key signaling molecule, phospholipase D, appears to regulate encystation. We provide evidence for the occurrence of meiosis during encystation, suggesting that stage conversion may play a key role in recombination between strains.

Conclusions

Our analysis demonstrates that a number of core processes are common to encystation between distantly related parasites, including meiosis, lipid signaling and RNA modification. These data provide a foundation for understanding the developmental cascade in the important human pathogen E. histolytica and highlight conserved processes more widely relevant in enteric pathogens.
Whole-genome DNA/RNA sequencing identifies truncating mutations in RBCK1 in a novel Mendelian disease with neuromuscular and cardiac involvement
Authors: Wang Kai , Kim Cecilia , Bradfield Jonathan , Guo Yunfei , Toskala Elina , Otieno Frederick G , Hou Cuiping , Thomas Kelly , Cardinale Christopher , Lyon Gholson J , Golhar Ryan , Hakonarson Hakon
Published: July 2013

Background

Whole-exome sequencing has identified the causes of several Mendelian diseases by analyzing multiple unrelated cases, but it is more challenging to resolve the cause of extremely rare and suspected Mendelian diseases from individual families. We identified a family quartet with two children, both affected with a previously unreported disease, characterized by progressive muscular weakness and cardiomyopathy, with normal intelligence. During the course of the study, we identified one additional unrelated patient with a comparable phenotype.

Methods

We performed whole-genome sequencing (Complete Genomics platform), whole-exome sequencing (Agilent SureSelect exon capture and Illumina Genome Analyzer II platform), SNP genotyping (Illumina HumanHap550 SNP array) and Sanger sequencing on blood samples, as well as RNA-Seq (Illumina HiSeq platform) on transformed lymphoblastoid cell lines.

Results

From whole-genome sequence data, we identified RBCK1, a gene encoding an E3 ubiquitin-protein ligase, as the most likely candidate gene, with two protein-truncating mutations in probands in the first family. However, exome data failed to nominate RBCK1 as a candidate gene, due to poor regional coverage. Sanger sequencing identified a private homozygous splice variant in RBCK1 in the proband in the second family, yet SNP genotyping revealed a 1.2Mb copy-neutral region of homozygosity covering RBCK1. RNA-Seq confirmed aberrant splicing of RBCK1 transcripts, resulting in truncated protein products.

Conclusions

While the exact mechanism by which these mutations cause disease is unknown, our study represents an example of how the combined use of whole-genome DNA and RNA sequencing can identify a disease-predisposing gene for a novel and extremely rare Mendelian disease.
Pathprinting: An integrative approach to understand the functional basis of disease
Authors: Altschuler Gabriel M , Hofmann Oliver , Kalatskaya Irina , Payne Rebecca , Ho Sui Shannan J , Saxena Uma , Krivtsov Andrei V , Armstrong Scott A , Cai Tianxi , Stein Lincoln , Hide Winston A
Published: July 2013

New strategies to combat complex human disease require systems approaches to biology that integrate experiments from cell lines, primary tissues and model organisms. We have developed Pathprint, a functional approach that compares gene expression profiles in a set of pathways, networks and transcriptionally regulated targets. It can be applied universally to gene expression profiles across species. Integration of large-scale profiling methods and curation of the public repository overcomes platform, species and batch effects to yield a standard measure of functional distance between experiments. We show that pathprints combine mouse and human blood developmental lineage, and can be used to identify new prognostic indicators in acute myeloid leukemia. The code and resources are available at http://compbio.sph.harvard.edu/hidelab/pathprint
A comparison of the reparative and angiogenic properties of mesenchymal stem cells derived from the bone marrow of BALB/c and C57/BL6 mice in a model of limb ischemia
Authors: Cunha Flavia Franco , Martins Leonardo , Martin Priscila Keiko Matsumoto , Stilhano Roberta Sessa , Han Sang Won
Published: July 2013

Introduction

BALB/c mice and C57/BL6 mice have different abilities to recover from ischemia. C57/BL6 mice display increased vessel collateralization and vascular endothelial growth factor expression with a consequent rapid recovery from ischemia compared with BALB/c mice. Mesenchymal stem cells (MSCs) are one of the main cell types that contribute to the recovery from ischemia because, among their biological activities, they produce several proangiogenic paracrine factors and differentiate into endothelial cells. The objective of this study was to evaluate whether the MSCs of these two mouse strains have different inductive capacities for recovering ischemic limbs.

Methods

MSCs from these two strains were obtained from the bone marrow, purified and characterized before being used for in vivo experiments. Limb ischemia was surgically induced in BALB/c mice, and MSCs were injected on the fifth day. The evolution of limb necrosis was evaluated over the subsequent month. Muscle strength was assessed on the 30th day after the injection, and then the animals were sacrificed to determine the muscle mass and perform histological analyses to detect cellular infiltration, capillary and microvessel densities, fibrosis, necrosis and tissue regeneration.

Results

The MSCs from both strains promoted high level of angiogenesis similarly, resulting in good recovery from ischemia. However, BALB/c MSCs promoted more muscle regeneration (57%) than C57/BL6 MSCs (44%), which was reflected in the increased muscle strength (0.79 N versus 0.45 N).

Conclusion

The different genetic background of MSCs from BALB/c mice and C57/BL6 mice was not a relevant factor in promoting angiogenesis of limb ischemia, because both cells showed a similar angiogenic activity. These cells also showed a potential myogenic effect, but the stronger effect promoted by BALB/c MSCs indicates that the different genetic background of MSCs was more relevant in myogenesis than angiogesis.
Post-traumatic stress symptoms among former child soldiers in Sierra Leone: follow-up study
Authors: Betancourt Theresa S. , Newnham Elizabeth A. , McBain Ryan , Brennan Robert T.
Published: July 2013

Background

Former child soldiers are at risk of developing post-traumatic stress disorder (PTSD); however, the trajectory of symptoms has yet to be examined.

Aims

The risk and protective factors associated with PTSD symptom change among former child soldiers in Sierra Leone were investigated.

Method

Data from 243 former child soldiers (mean age 16.6 years, 30% female) were analysed.

Results

Self-reported rates of possible PTSD using standard cut-off points declined from 32% to 16% 4 years later (P<0.05). Symptoms of PTSD at baseline were significantly associated with war experiences (P<0.01) and post-conflict family abuse (P<0.001). Reliable improvement in symptoms was reported by 30%. In growth models examining symptom change, worsening of symptoms was associated with death of a parent (P<0.05) and post-conflict stigma (P<0.001). Protective effects were observed for increases in family acceptance (P<0.001).

Conclusions

The findings indicated improvement in PTSD symptoms among former child soldiers despite limited access to care. Family and community support played a vital part in promoting psychological adjustment.
Determinants for undetected dementia and late-life depression
Authors: Chen Ruoling , Hu Zhi , Chen Ruo-Li , Ma Ying , Zhang Dongmei , Wilson Kenneth
Published: July 2013

Background

Determinants for undetected dementia and late-life depression have been not well studied.

Aims

To investigate risk factors for undetected dementia and depression in older communities.

Method

Using the method of the 10/66 algorithm, we interviewed a random sample of 7072 participants aged ⩽60 years in six provinces of China during 2007–2011. We documented doctor-diagnosed dementia and depression in the interview. Using the validated 10/66 algorithm we diagnosed dementia (n= 359) and depression (n= 328).

Results

We found that 93.1% of dementia and 92.5% of depression was undetected. Both undetected dementia and depression were significantly associated with low levels of education and occupation, and living in a rural area. The risk of undetected dementia was also associated with ‘help available when needed‘, and inversely, with a family history of mental illness and having functional impairment. Undetected depression was significantly related to female gender, low income, having more children and inversely with having heart disease.

Conclusions

Older adults in China have high levels of undetected dementia and depression. General socioeconomic improvement, associated with mental health education, targeting high-risk populations are likely to increase detection of dementia and depression in older adults, providing a backdrop for culturally acceptable service development.
Effect of prior treatment with antipsychotic long-acting injection on randomised clinical trial treatment outcomes
Authors: Barnes Thomas R. E. , Drake Richard J. , Dunn Graham , Hayhurst Karen P. , Jones Peter B. , Lewis Shôn W.
Published: July 2013

Background

It is uncertain whether antipsychotic long-acting injection (LAI) medication in schizophrenia is associated with better clinical outcomes than oral preparations.

Aims

To examine the impact of prior treatment delivery route on treatment outcomes and whether any differences are moderated by adherence.

Method

Analysis of data from two pragmatic 1-year clinical trials in which patients with schizophrenia were randomised to either an oral first-generation antipsychotic (FGA), or a non-clozapine second-generation antipsychotic (SGA, CUtLASS 1 study), or a non-clozapine SGA or clozapine (CUtLASS 2 study).

Results

Across both trials, 43% (n = 155) of participants were prescribed an FGA-LAI before randomisation. At 1-year follow-up they showed less improvement in quality of life, symptoms and global functioning than those randomised from oral medication. This difference was confined to patients rated as less than consistently adherent pre-randomisation. The relatively poor improvement in the patients prescribed an LAI pre-randomisation was ameliorated if they had been randomised to clozapine rather than another SGA. There was no advantage to being randomly assigned from an LAI at baseline to a non-clozapine oral SGA rather than an oral FGA.

Conclusions

A switch at randomisation from an LAI to an oral antipsychotic was associated with poorer clinical and functional outcomes at 1-year follow-up compared with switching from one oral antipsychotic to another. This effect appears to be moderated by adherence, and may not extend to switching to clozapine. This has implications for clinical trial design: the drug from which a participant is randomised may have a greater effect than the drug to which they are randomised.
Lats2 phosphorylates p21/CDKN1A after UV irradiation and regulates apoptosis
Authors: Suzuki Hirokazu , Yabuta Norikazu , Okada Nobuhiro , Torigata Kosuke , Aylon Yael , Oren Moshe , Nojima Hiroshi
Published: July 2013

LATS2 (Large tumor suppressor 2), a member of the conserved AGC Ser/Thr (S/T) kinase family, is a human tumor suppressor gene. Here, we show that in response to ultraviolet radiation, Lats2 is phosphorylated by Chk1 at Ser835 (S835), which is located in the kinase domain of Lats2. This phosphorylation enhances Lats2 kinase activity. Subsequently, Lats2 phosphorylates p21 at S146. p21 (CDKN1A) is a cyclin-dependent kinase (CDK) inhibitor, which not only regulates the cell cycle by inhibition of CDK, but also inhibits apoptosis by binding to procaspase-3 in the cytoplasm. Phosphorylation by Lats2 induces degradation of p21 and promotes apoptosis. Accordingly, Lats2 overexpression induces p21 degradation, activation of caspase-3 and caspase-9, and apoptosis. These findings describe a novel Lats2-dependent mechanism for induction of cell death in response to severe DNA damage.
ZO-1 recruitment to α-catenin: a novel mechanism for coupling the assembly of tight junctions to adherens junctions
Authors: Maiers Jessica L. , Peng Xiao , Fanning Alan S. , DeMali Kris A.
Published: July 2013

The formation of a barrier between epithelial cells is a fundamental determinant of cellular homeostasis, protecting underlying cells against pathogens, dehydration, and damage. Assembly of the tight junction barrier is dependent upon neighboring epithelial cells binding to one another and forming adherens junctions, but the mechanism for how these processes are linked is poorly understood. Using a knockdown/substitution system, we studied if ZO-1 binding to α-catenin is required for coupling tight junction assembly to adherens junctions. We generated an α-catenin point mutant that does not bind ZO-1. We found that preventing ZO-1 binding to α-catenin severely disrupted the assembly and maintenance of an epithelial barrier by altering the mobility of ZO-1 and organization of the actin cytoskeleton. Under these conditions, the adherens junctions did not appear to be disrupted. Thus, our study identifies α-catenin binding to ZO-1 as a novel mechanism for coupling the tight junction barrier machinery to adherens junction adhesion complex.