bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of anoikis in human intestinal epithelial cells: differentiation state-selective roles of α2β1, α3β1, α5β1, and α6β4 integrins
Authors: Beauséjour Marco , Thibodeau Sonya , Demers Marie-Josée , Bouchard Véronique , Gauthier Rémy , Beaulieu Jean-François , Vachon Pierre H
Published: December 2013

Background

Regulation of anoikis in human intestinal epithelial cells (IECs) implicates differentiation state-specific mechanisms. Human IECs express distinct repertoires of integrins according to their state of differentiation. Therefore, we investigated whether α2β1, α3β1, α5β1, and α6β4 integrins perform differentiation state-specific roles in the suppression of IEC anoikis.

Results

Human (HIEC, Caco-2/15) IECs were exposed to specific antibodies that block the binding activity of integrin subunits (α2, α3, α5, α6, β1 or β4) to verify whether or not their inhibition induced anoikis. The knockdown of α6 was also performed by shRNA. Additionally, apoptosis/anoikis was induced by pharmacological inhibition of Fak (PF573228) or Src (PP2). Anoikis/apoptosis was assayed by DNA laddering, ISEL, and/or caspase activity (CASP-8, -9, or -3). Activation levels of Fak and Src, as well as functional Fak-Src interactions, were also assessed. We report herein that differentiated IECs exhibit a greater sensitivity to anoikis than undifferentiated ones. This involves an earlier onset of anoikis when kept in suspension, as well as significantly greater contributions from β1 and β4 integrins in the suppression of anoikis in differentiated cells, and functional distinctions between β1 and β4 integrins in engaging both Fak and Src, or Src only, respectively. Likewise, Fak performs significantly greater contributions in the suppression of anoikis in differentiated cells. Additionally, we show that α2β1 and α5β1 suppress anoikis in undifferentiated cells, whereas α3β1 does so in differentiated ones. Furthermore, we provide evidence that α6β4 contributes to the suppression of anoikis in a primarily α6 subunit-dependent manner in undifferentiated cells, whereas this same integrin in differentiated cells performs significantly greater contributions in anoikis suppression than its undifferentiated state-counterpart, in addition to doing so through a dependence on both of its subunits.

Conclusions

Our findings indicate that the suppression of human IEC anoikis implicates differentiation state-selective repertoires of integrins, which in turn results into distinctions in anoikis regulation, and sensitivity, between undifferentiated and differentiated IECs. These data further the functional understanding of the concept that the suppression of anoikis is subjected to cell differentiation state-selective mechanisms.
Genome-wide analysis of coordinated transcript abundance during seed development in different Brassica rapa morphotypes
Authors: Basnet Ram Kumar , Moreno-Pachon Natalia , Lin Ke , Bucher Johan , Visser Richard G F , Maliepaard Chris , Bonnema Guusje
Published: December 2013

Background

Brassicaseeds are important as basic units of plant growth and sources of vegetable oil. Seed development is regulated by many dynamic metabolic processes controlled by complex networks of spatially and temporally expressed genes. We conducted a global microarray gene co-expression analysis by measuring transcript abundance of developing seeds from two diverseB. rapamorphotypes: a pak choi (leafy-type) and a yellow sarson (oil-type), and two of their doubled haploid (DH) progenies, (1) to study the timing of metabolic processes in developing seeds, (2) to explore the major transcriptional differences in developing seeds of the two morphotypes, and (3) to identify the optimum stage for a genetical genomics study inB. rapaseed.

Results

Seed developmental stages were similar in developing seeds of pak choi and yellow sarson ofB. rapa; however, the colour of embryo and seed coat differed among these two morphotypes. In this study, most transcriptional changes occurred between 25 and 35 DAP, which shows that the timing of seed developmental processes inB. rapais at later developmental stages than in the related speciesB. napus. Using a Weighted Gene Co-expression Network Analysis (WGCNA), we identified 47 “gene modules”, of which 27 showed a significant association with temporal and/or genotypic variation. An additional hierarchical cluster analysis identified broad spectra of gene expression patterns during seed development. The predominant variation in gene expression was according to developmental stages rather than morphotype differences. Since lipids are the major storage compounds ofBrassicaseeds, we investigated in more detail the regulation of lipid metabolism. Four co-regulated gene clusters were identified with 17 putativecis-regulatory elements predicted in their 1000 bp upstream region, either specific or common to different lipid metabolic pathways.

Conclusions

This is the first study of genome-wide profiling of transcript abundance during seed development inB. rapa. The identification of key physiological events, major expression patterns, and putativecis-regulatory elements provides useful information to construct gene regulatory networks inB. rapadeveloping seeds and provides a starting point for a genetical genomics study of seed quality traits.
Morphogenesis-regulated localization of protein kinase A to genomic sites in Candida albicans
Authors: Schaekel Alida , Desai Prashant R , Ernst Joachim F
Published: December 2013

Background

The human fungal pathogen Candida albicans is able to undergo morphogenesis from a yeast to a hyphal growth form. Protein kinase A (PKA) isoforms Tpk1 and Tpk2 promote hyphal growth in a signalling pathway via the transcription factor Efg1.

Results

C. albicans strains producing epitope-tagged Tpk1 or Tpk2 were used in genome-wide chromatin immunoprecipitation on chip (ChIP chip) to reveal genomic binding sites. During yeast growth, both PKA isoforms were situated primarily within ORFs but moved to promoter regions shortly after hyphal induction. Binding sequences for Tpk2 greatly exceeded Tpk1 sites and did not coincide with binding of the PKA regulatory subunit Bcy1. Consensus binding sequences for Tpk2 within ORFs included ACCAC and CAGCA motifs that appeared to bias codon usage within the binding regions. Promoter residency of Tpk2 correlated with the transcript level of the corresponding gene during hyphal morphogenesis and occurred near Efg1 binding sites, mainly on genes encoding regulators of morphogenesis.

Conclusions

PKA isoforms change their genomic binding sites from ORF to promoter regions during yeast-hyphal morphogenesis. Tpk2 binds preferentially to promoters of genes encoding regulators of cellular morphogenesis.
Translational profiling in childhood acute lymphoblastic leukemia: no evidence for glucocorticoid regulation of mRNA translation
Authors: Aneichyk Tatsiana , Bindreither Daniel , Mantinger Christine , Grazio Daniela , Goetsch Katrin , Kofler Reinhard , Rainer Johannes
Published: December 2013

Background

Glucocorticoids (GCs) are natural stress induced steroid hormones causing cell cycle arrest and cell death in lymphoid tissues. Therefore they are the central component in the treatment of lymphoid malignancies, in particular childhood acute lymphoblastic leukemia (chALL). GCs act mainlyviaregulating gene transcription, which has been intensively studied by us and others. GC control of mRNA translation has also been reported but has never been assessed systematically. In this study we investigate the effect of GCs on mRNA translation on a genome-wide scale.

Results

Childhood T- (CCRF-CEM) and precursor B-ALL (NALM6) cells were exposed to GCs and subjected to “translational profiling”, a technique combining sucrose-gradient fractionation followed by Affymetrix Exon microarray analysis of mRNA from different fractions, to assess the translational efficiency of the expressed genes. Analysis of GC regulation in ribosome-bound fractionsversustranscriptional regulation revealed no significant differences, i.e., GC did not entail a significant shift between ribosomal bound and unbound mRNAs.

Conclusions

In the present study we analyzed for the first time possible effects of GC on the translational efficiency of expressed genes in two chALL model systems employing whole genome polysome profiling. Our results did not reveal significant differences in translational efficiency of expressed genes thereby arguing against a potential widespread regulatory effect of GCs on translation at least in the investigatedin vitrosystems.
Hyperosmotic response of streptococcus mutans: from microscopic physiology to transcriptomic profile
Authors: Liu Chengcheng , Niu Yulong , Zhou Xuedong , Zhang Keke , Cheng Lei , Li Mingyun , Li Yuqing , Wang Renke , Yang Yi , Xu Xin
Published: December 2013

Background

Oral streptococci metabolize carbohydrate to produce organic acids, which not only decrease the environmental pH, but also increase osmolality of dental plaque fluid due to tooth demineralization and consequent calcium and phosphate accumulation. Despite these unfavorable environmental changes, the bacteria continue to thrive. The aim of this study was to obtain a global view on strategies taken by Streptococcus mutans to deal with physiologically relevant elevated osmolality, and perseveres within a cariogenic dental plaque.

Results

We investigated phenotypic change of S. mutans biofilm upon hyperosmotic challenge. We found that the hyperosmotic condition was able to initiate S. mutans biofilm dispersal by reducing both microbial content and extracellular polysaccharides matrix. We then used whole-genome microarray with quantitative RT-PCR validation to systemically investigate the underlying molecular machineries of this bacterium in response to the hyperosmotic stimuli. Among those identified 40 deferentially regulated genes, down-regulation of gtfB and comC were believed to be responsible for the observed biofilm dispersal. Further analysis of microarray data showed significant up-regulation of genes and pathways involved in carbohydrate metabolism. Specific genes involved in heat shock response and acid tolerance were also upregulated, indicating potential cross-talk between hyperosmotic and other environmental stress.

Conclusions

Hyperosmotic condition induces significant stress response on S. mutans at both phenotypic and transcriptomic levels. In the meantime, it may take full advantage of these environmental stimuli to better fit the fluctuating environments within oral cavity, and thus emerges as numeric-predominant bacterium under cariogenic conditions.
A high-throughput virus-induced gene silencing protocol identifies genes involved in multi-stress tolerance
Authors: Ramegowda Venkategowda , Senthil-kumar Muthappa , Udayakumar Makarla , Mysore Kirankumar S
Published: December 2013

Background

Understanding the function of a particular gene under various stresses is important for engineering plants for broad-spectrum stress tolerance. Although virus-induced gene silencing (VIGS) has been used to characterize genes involved in abiotic stress tolerance, currently available gene silencing and stress imposition methodology at the whole plant level is not suitable for high-throughput functional analyses of genes. This demands a robust and reliable methodology for characterizing genes involved in abiotic and multi-stress tolerance.

Results

Our methodology employs VIGS-based gene silencing in leaf disks combined with simple stress imposition and effect quantification methodologies for easy and faster characterization of genes involved in abiotic and multi-stress tolerance. By subjecting leaf disks from gene-silenced plants to various abiotic stresses and inoculating silenced plants with various pathogens, we show the involvement of several genes for multi-stress tolerance. In addition, we demonstrate that VIGS can be used to characterize genes involved in thermotolerance. Our results also showed the functional relevance of NtEDS1 in abiotic stress, NbRBX1 and NbCTR1 in oxidative stress; NtRAR1 and NtNPR1 in salinity stress; NbSOS1 and NbHSP101 in biotic stress; and NtEDS1, NbETR1, NbWRKY2 and NbMYC2 in thermotolerance.

Conclusions

In addition to widening the application of VIGS, we developed a robust, easy and high-throughput methodology for functional characterization of genes involved in multi-stress tolerance.
The reproductive strategy of a pollinator-limited Himalayan plant, Incarvillea mairei(Bignoniaceae)
Authors: Ai Honglian , Zhou Wei , Xu Kun , Wang Hong , Li Dezhu
Published: December 2013

Background

Plants may adapt to alpine habitats by specialization in the reproductive strategy and functional aspects of their flowers and pollination systems. Alpine habitats reduce the opportunities for cross-pollination in a relatively high proportion of alpine plant species, and self-pollination may be favored in these adverse conditions. Here, we investigated the mating system and pollination of Incarvillea mairei, a perennial Himalayan herb typically found at altitudes between 3000 and 4500 m.

Results

Analyses of floral morphology, observation of plant-pollinator interactions, and hand pollination experiments were conducted in three natural populations. Outcrossing rates and effective numbers of pollen donors were assessed in 45 open-pollinated families by using progeny analysis based on seven microsatellite markers. Incarvillea mairei displayed a set of apparently specialized floral traits, the stigma is sensitive to touch and close immediately and its reopening allows a second opportunity for the receipt of pollen. The species is fully self-compatible but employs a predominantly outcrossing mating system according to parentage analysis (tm > 0.9). Fruit set was low (26.3%), whereas seed set was high (67.2%), indicating that this species suffers pollinator limitation. Its main effective pollinator was Halictus sp., and visitation frequency was low.

Conclusions

Floral features such as having a sensitive stigma and anther-prongs, in conjunction with pollinator behavior, function together contributing to a set of unique reproductive adaptations that enhance outcrossing success. The increased floral longevity and high pollination efficiency operated as compensatory mechanisms to counteract low pollinator visitation frequency.
A survey of Preventive Measures Used and their Impact on Central Line-Associated Bloodstream Infections (CLABSI) in Intensive Care Units (SPIN-BACC)
Authors: Gonzales Milagros , Rocher Isabelle , Fortin Élise , Fontela Patricia , Kaouache Mohammed , Tremblay Claude , Frenette Charles , Quach Caroline
Published: December 2013

Background

The Quebec central line-associated bloodstream infections (CLABSI) in intensive care units (ICUs) Surveillance Program saw a decrease in CLABSI rates in most ICUs. Given the surveillance trends observed in recent years, we aimed to determine what preventive measures have been implemented, if compliance to measures was monitored and its impact on CLABSI incidence rates.

Methods

All hospitals participating in the Quebec healthcare-associated infections surveillance program (SPIN-BACC – n = 48) received a 77-question survey about preventive measures implemented and monitored in their ICU. The questionnaire was validated for construct, content, face validity, and reliability. We used Poisson regression to measure the association between compliance monitoring to preventive measures and CLABSI rates.

Results

Forty-two (88%) eligible hospitals completed the survey. Two components from the maximum barrier precautions were used less optimally: cap (88%) and full sterile body drape (71%). Preventive measures reported included daily review of catheter need (79%) and evaluation of insertion site for the presence of inflammation (90%). Two hospitals rewired lines even if an infection was suspected or documented.

In adult ICUs, there was a statistically significant greater decrease in CLABSI rates in ICUs that monitored compliance to preventive insertion measures, after adjusting for teaching status and the number of hospital beds (p = 0.036).

Conclusions

Hospitals participating to the SPIN-BACC program follow recommendations for CLABSI prevention, but only a minority locally monitor their application. Compliance monitoring of preventive measures for catheter insertion was associated with a decrease in CLABSI incidence rates.
Incarceration is associated with used syringe lending among active injection drug users with detectable plasma HIV-1 RNA: a longitudinal analysis
Authors: Milloy M-J , Kerr Thomas , Salters Kate , Samji Hasina , Guillemi Silvia , Montaner Julio , Wood Evan
Published: December 2013

Background

Informed by recent studies demonstrating the central role of plasma HIV-1 RNA viral load (VL) on HIV transmission, interventions to employ HIV antiretroviral treatment as prevention (TasP) are underway. To optimize these efforts, evidence is needed to identify factors associated with both non-suppressed VL and HIV risk behaviours. Thus, we sought to assess the possible role played by exposure to correctional facilities on VL non-suppression and used syringe lending among HIV-seropositive people who use injection drugs (PWID).

Methods

We used data from the ACCESS study, a community-recruited prospective cohort. We used longitudinal multivariate mixed-effects analyses to estimate the relationship between incarceration and plasma HIV-1 RNA > 500 copies/mL among antiretroviral therapy (ART)-exposed active PWID and, during periods of non-suppression, the relationship between incarceration and used syringe lending.

Results

Between May 1996 and March 2012, 657 ART-exposed PWID were recruited. Incarceration was independently associated with higher odds of VL non-suppression (Adjusted Odds Ratio [AOR] = 1.54, 95% Confidence Interval [95% CI]: 1.10, 2.16). In a separate multivariate model restricted to periods of VL non-suppression, incarceration was independently associated with lending used syringes (AOR = 1.81, 95% CI: 1.03, 3.18).

Conclusions

The current findings demonstrate that incarceration is associated with used syringe lending among active PWID with detectable plasma HIV-1 RNA. Our results provide a possible pathway for the commonly observed association between incarceration and increased risk of HIV transmission. Our results suggest that alternatives to incarceration of non-violent PWID and evidence-based combination HIV prevention interventions for PWID within correctional facilities are urgently needed.
Influence of FTO variants on obesity, inflammation and cardiovascular disease risk biomarkers in Spanish children: a case–control multicentre study
Authors: Olza Josune , Ruperez Azahara I , Gil-Campos Mercedes , Leis Rosaura , Fernandez-Orth Dietmar , Tojo Rafael , Cañete Ramon , Gil Angel , Aguilera Concepcion M
Published: December 2013

Background

Variants in the FTO gene have been associated with obesity in children, but this association has not been shown with other biomarkers. We assessed the association of 52 FTO polymorphisms, spanning the whole gene, with obesity and estimated the influence of these polymorphisms on anthropometric, clinical and metabolic parameters as well as inflammation and cardiovascular disease (CVD) risk biomarkers among Spanish children.

Methods

A multicentre case–control study was conducted in 534 children (292 obese and 242 with normal-BMI). Anthropometric, clinical, metabolic, inflammation and CVD risk markers were compared using the Student’s t-test for unpaired samples. The genotype relative risk was assessed by comparing the obese and normal-BMI group, calculating the odds ratio. The association of each SNP with phenotypic parameters was analysed using either logistic or linear regression analysis.

Results

All anthropometric, clinical and metabolic factors as well as inflammatory and CVD risk biomarkers were higher in the obese than in the normal-BMI group, except adiponectin and HDL-c that were lower, and glucose, LDL-c, and metalloproteinase-9 that did not show difference. Four polymorphisms (rs9935401, rs9939609, rs9928094 and rs9930333) were positively associated with obesity and in linkage disequilibrium between each other; the haplotype including the risk alleles of these polymorphisms showed a high risk for obesity. The rs8061518 was negatively associated with obesity and the haplotype including this SNP and rs3826169, rs17818902 and rs7190053 showed a decreased risk for obesity. Additionally, the rs8061518 was associated with weight, diastolic blood pressure, insulin, homeostatic model assessment of insulin resistance, leptin, and active plasminogen inhibitor activator-1 after sex and age adjustment; however, after an additional BMI adjustment, this polymorphism remained associated only with leptin.

Conclusions

We validated the previous reported association of genetic variability in intron 1 of the FTO gene with the risk of obesity and found no association with other related traits in this region of the gene. We have observed strong statistical evidence for an association of rs8061518 in intron 3 of the gene with decreased risk of obesity and low concentration of leptin.
Infusion of autologous bone marrow mononuclear cells leads to transient reduction in proteinuria in treatment refractory patients with Idiopathic membranous nephropathy
Authors: Sengupta Upal , Kumar Vinod , Yadav Ashok K , Marwaha Neelam , Kohli Harbir S , Sakhuja Vinay , Jha Vivekanand
Published: December 2013

Background

The current treatment options for idiopathic membranous nephropathy (IMN) carry significant toxicity. In this prospective, observational pilot study, we used single time infusion of bone marrow derived autologous mononuclear cells (MNCs) in adult patients with treatment refractory IMN.

Methods

Twelve patients of biopsy proven IMN who had failed a cyclical 6-month regimen of steroid and cyclophosphamide were enrolled in the study. Bone-marrow was harvested from the iliac crest and underwent processing to isolate MNCs. Cells were counted and subjected to viability testing before being infused through a peripheral vein on the same day. After the infusion, subjects were followed up monthly for the next six months. Supportive treatment including angiotensin antagonists and statins was continued throughout the study period.

Result

The proteinuria, serum albumin and creatinine values at entry were 2.97 ± 0.6 gm/1.73 m2/d, 2.27 ± 1.1 gm/l and 0.9 ± 0.8 mg/dl respectively. There was a reduction in proteinuria (p < 0.0001), and increase in serum albumin (p = 0.001) at 1 month, with 64% of the subjects showing >50% reduction in proteinuria. However, the response was ill sustained. At 6 months, only 2 patients had >50% reduction. Serum creatinine remained stable throughout the study period. No infusion related side effects were noted.

Conclusion

Autologous mononuclear cell infusion leads to transitory reduction in proteinuria and improvement in serum albumin in treatment refractory IMN. This effect, however, is transient. Whether this can be overcome by repeated infusion of cultured mesenchymal cells needs to be investigated.
Predicting risk of mortality in dialysis patients: a retrospective cohort study evaluating the prognostic value of a simple chest X-ray
Authors: Bohn Ethan , Tangri Navdeep , Gali Brent , Henderson Blair , Sood Manish M , Komenda Paul , Rigatto Claudio
Published: December 2013

Background

Clinical outcomes of dialysis patients are variable, and improved knowledge of prognosis would inform decisions regarding patient management. We assessed the value of simple, chest X-ray derived measures of cardiac size (cardiothoracic ratio (CTR)) and vascular calcification (Aortic Arch Calcification (AAC)), in predicting death and improving multivariable prognostic models in a prevalent cohort of hemodialysis patients.

Methods

Eight hundred and twenty-four dialysis patients with one or more postero-anterior (PA) chest X-ray were included in the study. Using a validated calcification score, the AAC was graded from 0 to 3. Cox proportional hazards models were used to assess the association between AAC score, CTR, and mortality. AAC was treated as a categorical variable with 4 levels (0,1,2, or 3). Age, race, diabetes, and heart failure were adjusted for in the multivariable analysis. The criterion for statistical significance was p<0.05.

Results

The median CTR of the sample was 0.53 [IQR=0.48,0.58] with calcification scores as follows: 0 (54%), 1 (24%), 2 (17%), and 3 (5%). Of 824 patients, 152 (18%) died during follow-up. Age, sex, race, duration of dialysis, diabetes, heart failure, ischemic heart disease and baseline serum creatinine and phosphate were included in a base Cox model. Both CTR (HR 1.78[1.40,2.27] per 0.1 unit change), area under the curve (AUC)=0.60[0.55,0.65], and AAC (AAC 3 vs 0 HR 4.35[2.38,7.66], AAC 2 vs 0 HR 2.22[1.41,3.49], AAC 1 vs 0 HR 2.43[1.64,3.61]), AUC=0.63[0.58,0.68]) were associated with death in univariate Cox analysis. CTR remained significant after adjustment for base model variables (adjusted HR 1.46[1.11,1.92]), but did not increase the AUC of the base model (0.71[0.66,0.76] vs. 0.71[0.66,0.76]) and did not improve net reclassification performance (NRI=0). AAC also remained significant on multivariable analysis, but did not improve net reclassification (NRI=0). All ranges were based on 95% confidence intervals.

Conclusions

Neither CTR nor AAC assessed on chest x-ray improved prediction of mortality in this prevalent cohort of dialysis patients. Our data do not support the clinical utility of X-ray measures of cardiac size and vascular calcification for the purpose of mortality prediction in prevalent hemodialysis patients. More advanced imaging techniques may be needed to improve prognostication in this population.
Severe pan-uveitis in a patient treated with vemurafenib for metastatic melanoma
Authors: Wolf Sanne EJ , Meenken Christina , Moll Annette C , Haanen John B , van der Heijden Michiel S
Published: December 2013

Background

Vemurafenib, an inhibitor of genetically activated BRAF, is now commonly prescribed for metastatic melanoma harboring a BRAF mutation. Reports on side effects have focused on cutaneous complications. We here present a case of a severe pan-uveitis associated with vemurafenib use.

Case presentation

A 63-year old female was treated with the BRAF inhibitor vemurafenib for metastatic melanoma. After seven weeks of treatment, she developed near-complete visual loss in the course of a few days, as a result of severe uveitis. Vemurafenib had to be discontinued and systemic and topical corticosteroids were initiated. The visual symptoms improved slowly, however the cerebral metastases progressed and the patient died from her disease.

Conclusion

Treatment with vemurafenib has become an important component of standard clinical care for patients with metastatic melanoma. In addition, it is one of the best examples of genotype-directed therapy. This case illustrates that vemurafenib-induced uveitis can develop fast and be slow to resolve. Awareness of this potentially severe side effect is of major importance to oncologists and aggressive treatment should be considered.
Breast cancers with high DSS1 expression that potentially maintains BRCA2 stability have poor prognosis in the relapse-free survival
Authors: Rezano Andri , Kuwahara Kazuhiko , Yamamoto-Ibusuki Mutsuko , Kitabatake Masahiro , Moolthiya Penpak , Phimsen Suchada , Suda Taiji , Tone Shigenobu , Yamamoto Yutaka , Iwase Hirotaka , Sakaguchi Nobuo
Published: December 2013

Background

Genetic BRCA2 insufficiency is associated with breast cancer development; however, in sporadic breast cancer cases, high BRCA2 expression is paradoxically correlated with poor prognosis. Because DSS1, a mammalian component of the transcription/RNA export complex, is known to stabilize BRCA2, we investigated how the expression of DSS1 is associated with clinical parameters in breast cancers.

Methods

DSS1 mRNA and p53 protein were examined by RT-PCR and immunohistochemical staining of breast cancer specimens to classify DSS1
high and DSS1
low or p53high and p53low groups. Patient survival was compared using Kaplan-Meier method. DSS1
high or DSS1
low breast cancer cells were prepared by retroviral cDNA transfection or DSS1 siRNA on proliferation, cell cycle progression, and survival by flow cytometric analyses with or without anti-cancer drugs.

Results

In comparison to patients with low levels of DSS1, high-DSS1 patients showed a poorer prognosis, with respect to relapse-free survival period. The effect of DSS1 was examined in breast cancer cells in vitro. DSS1 high-expression reduces the susceptibility of MCF7 cells to DNA-damaging drugs, as observed in cell cycle and apoptosis analyses. DSS1 knockdown, however, increased the susceptibility to the DNA-damaging drugs camptothecin and etoposide and caused early apoptosis in p53 wild type MCF7 and p53-insufficient MDA-MB-231 cells. DSS1 knockdown suppresses the proliferation of drug-resistant MDA-MB-231 breast cancer cells, particularly effectively in combination with DNA-damaging agents.

Conclusion

Breast cancers with high DSS1 expression have worse prognosis and shorter relapse-free survival times. DSS1 is necessary to rescue cells from DNA damage, but high DSS1 expression increases drug resistance. We suggest that DSS1 expression could be a useful marker for drug resistance in breast cancers, and DSS1 knockdown can induce tumor apoptosis when used in combination with DNA-damaging drugs.
Long-lasting response to electrochemotherapy in melanoma patients with cutaneous metastasis
Authors: Caracò Corrado , Mozzillo Nicola , Marone Ugo , Simeone Ester , Benedetto Lucia , Di Monta Gianluca , Di Cecilia Maria Luisa , Botti Gerardo , Ascierto Paolo Antonio
Published: December 2013

Background

Treatment of early and multiple cutaneous unresectable recurrences is a major therapeutic problem with around 80% of patients relapsing within 5 years. For lesions refractory to elective treatments, electrochemotherapy (ECT) involving electroporation combined with antineoplastic drug treatment appears to be a new potential option. This study was undertaken to analyze the short- and long-term responses of lesions treated with ECT with intravenous injection of bleomycin in melanoma patients with in-transit disease or distant cutaneous metastases.

Methods

Between June 2007 and September 2012, 60 patients with relapsed and refractory cutaneous melanoma metastases or in-transit disease underwent 100 courses of ECT with intravenous injection of bleomycin. Response to treatment was evaluated three months after ECT. A long-lasting response was defined as no cutaneous or in-transit relapse after a minimum of six months.

Results

Three months after ECT, a complete response was observed in 29 patients (48.4%), a partial response in 23 patients (38.3%) and no change or progressive disease in 8 patients (13.3%). The objective response rate of all treated lesions was 86.6%. Thirteen patients (44.8% of complete responders) experienced a long-lasting response after one ECT session and were disease-free after a mean duration of follow-up of 27.5 months.

Conclusions

The favorable outcome obtained in the present study demonstrates that ECT is a reliable, and effective procedure that provides long-term benefit in terms of curative and palliative treatment for unresectable cutaneous lesions without adversely impacting the quality of life of patients.
Effects of lifestyle and single nucleotide polymorphisms on breast cancer risk: a case–control study in Japanese women
Authors: Mizoo Taeko , Taira Naruto , Nishiyama Keiko , Nogami Tomohiro , Iwamoto Takayuki , Motoki Takayuki , Shien Tadahiko , Matsuoka Junji , Doihara Hiroyoshi , Ishihara Setsuko , Kawai Hiroshi , Kawasaki Kensuke , Ishibe Youichi , Ogasawara Yutaka , Komoike Yoshifumi , Miyoshi Shinichiro
Published: December 2013

Background

Lifestyle factors, including food and nutrition, physical activity, body composition and reproductive factors, and single nucleotide polymorphisms (SNPs) are associated with breast cancer risk, but few studies of these factors have been performed in the Japanese population. Thus, the goals of this study were to validate the association between reported SNPs and breast cancer risk in the Japanese population and to evaluate the effects of SNP genotypes and lifestyle factors on breast cancer risk.

Methods

A case–control study in 472 patients and 464 controls was conducted from December 2010 to November 2011. Lifestyle was examined using a self-administered questionnaire. We analyzed 16 breast cancer-associated SNPs based on previous GWAS or candidate-gene association studies. Age or multivariate-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were estimated from logistic regression analyses.

Results

High BMI and current or former smoking were significantly associated with an increased breast cancer risk, while intake of meat, mushrooms, yellow and green vegetables, coffee, and green tea, current leisure-time exercise, and education were significantly associated with a decreased risk. Three SNPs were significantly associated with a breast cancer risk in multivariate analysis: rs2046210 (per allele OR = 1.37 [95% CI: 1.11-1.70]), rs3757318 (OR = 1.33[1.05-1.69]), and rs3803662 (OR = 1.28 [1.07-1.55]). In 2046210 risk allele carriers, leisure-time exercise was associated with a significantly decreased risk for breast cancer, whereas current smoking and high BMI were associated with a significantly decreased risk in non-risk allele carriers.

Conclusion

In Japanese women, rs2046210 and 3757318 located near the ESR1 gene are associated with a risk of breast cancer, as in other Asian women. However, our findings suggest that exercise can decrease this risk in allele carriers.
Brain metastasis from hepatocellular carcinoma: the role of surgery as a prognostic factor
Authors: Han Moon-Soo , Moon Kyung-Sub , Lee Kyung-Hwa , Cho Sung-Bum , Lim Sa-Hoe , Jang Woo-Youl , Jung Tae-Young , Kim In-Young , Jung Shin
Published: December 2013

Background

The incidence of brain metastasis from hepatocellular carcinoma (HCC) is expected to increase as a result of prolonged survival due to the recent advances in HCC treatment. However, there is no definite treatment strategy for brain metastasis from HCC mainly due to its rarity and dismal prognosis. To provide helpful recommendations in treatment of brain metastasis from HCC, the authors aimed to identify prognostic factors that influence survival rates with a review of the recently published data.

Methods

Thirty-three cases of brain metastasis, whose incidence was 0.65%, were selected from a total of 5015 HCC patients and reviewed retrospectively in terms of clinical and radiological features.

Results

Median overall survival time after diagnosis of brain metastasis was 10.4 weeks (95% confidence interval [CI], 5.1-15.7 weeks) with 1-, 6- and 12-month survival rates, of 79%, 24% and 6%, respectively. Median survival of the patients treated with surgical resection or surgical resection followed by whole-brain radiation therapy (WBRT) (25.3 weeks; range, 15.8-34.8 weeks) was longer than that of the patients treated with gamma knife surgery (GKS), WBRT, or GKS followed by WBRT (10.4 weeks; range, 7.5-13.3 weeks) as well as that of patients treated with only steroids (1 week; range, 0.0-3.3 weeks) (p < 0.001). Child-Pugh’s classification A group had a longer median survival time than Child-Pugh’s classification B or C group (14.4 weeks vs 8.4 weeks, p = 0.038). RPA class I & II group had also a longer median survival time than RPA class III group did (13.4 weeks vs 2.4 weeks, p = 0.001). Surgical resection (hazard ratio [HR] 0.23, 95% CI 0.08-0.66, p = 0.006) and good liver function at the time of brain metastasis (HR 0.25, 95% CI 0.09-0.69, p = 0.007) were found to be the powerful prognostic factors for favorable survival in the multivariate analysis. In addition, presence of intratumoral hemorrhage was a statistically significant prognostic factor for survival.

Conclusion

Although HCC patients with brain metastasis showed a very dismal prognosis, surgical intervention was shown to lead to relative prolongation of the survival time, especially in those with preserved hepatic function.
Active trachoma two years after three rounds of azithromycin mass treatment in Cheha district Gurage zone, Southern Ethiopia
Authors: Admassu Fisseha , Bayu Samson , Bejiga Abebe , Amare Bemnet
Published: December 2013

Background

Azithromycin mass distribution was given to residents of Gurage zone Cheha district in 2004, 2005 and 2006 for three consecutive years with more than 90% coverage. The effect of treatment in the study community was not yet determined. The present study was therefore designed to assess the effect of azithromycin on the prevalence of active trachoma two years after three rounds of mass treatment of the community at Cheha district, Gurage zone.

Methods

A multistage stratified cluster random survey was employed to determine the prevalence of active trachoma among children aged 1 to 9. Selected children were examined for trachoma using the simplified WHO grading system and their households were assessed for trachoma risk factors.

Results

This survey demonstrated that the prevalence of active trachoma in the study community was 22.8% (95% CI 18.24% - 27.36%) that was lower than that of Southern Nations, Nationalities, and People's Regional prevalence (33.2%) in 2006. Only 27.6% (95% CI 25.7% - 30.1%) of the study population had a safe and clean water supply, whereas 42.7% (95% CI 39.8% - 46.2%) of the visited households had simple pit latrines.

Conclusion

This survey demonstrated that despite repeated mass oral azithromycin distributions, the prevalence of active trachoma was still high. Therefore, the other components of the SAFE strategy such as fly control program, improving the water sources, measures to improve face washing and construction of utilizable latrines that are being implemented through the health extension package have to be integrated with mass azithromycin treatment to eliminate active trachoma in the district.
Functional social support, psychological capital, and depressive and anxiety symptoms among people living with HIV/AIDS employed full-time
Authors: Liu Li , Pang Ran , Sun Wei , Wu Ming , Qu Peng , Lu Chunming , Wang Lie
Published: December 2013

Background

Psychological distress (e.g., depression and anxiety) has been regarded as the main cause of leaving work for people living with HIV/AIDS (PLWHA) in workplaces. This study aims to explore the associations of functional social support (FSS) and psychological capital (PC) with depressive and anxiety symptoms among PLWHA employed full-time.

Methods

This cross-sectional study was performed in Liaoning, China, during the period of December 2010–April 2011. The Center for Epidemiologic Studies Depression Scale, the Zung Self-Rating Anxiety Scale, the Duke-UNC Functional Social Support Questionnaire, and the Psychological Capital Questionnaire were completed by PLWHA employed full-time. Structural equation modeling was used to test the proposed relationships between variables. Asymptotic and resampling strategies were performed to explore the mediating roles of PC and its components (self-efficacy, hope, optimism, resilience).

Results

Of 320 participants surveyed, 66.3% had depressive symptoms, and 45.6% had anxiety symptoms. Significant negative associations of FSS and PC with depressive and anxiety symptoms were revealed. PC (a*b = −0.209, BCa 95% CI: -0.293, -0.137, p < 0.05), hope (a*b = −0.103, BCa 95% CI: -0.192, -0.034, p < 0.05), and optimism (a*b = −0.047, BCa 95% CI: -0.106, -0.008, p < 0.05) significantly mediated the association between FSS and depressive symptoms. PC (a*b = −0.151, BCa 95% CI: -0.224, -0.095, p < 0.05) and self-efficacy (a*b = −0.080, BCa 95% CI: -0.158, -0.012, p < 0.05) significantly mediated the FSS-anxiety symptoms association.

Conclusions

FSS and PC could help reduce depressive and anxiety symptoms among PLWHA employed full-time. PC fully mediates the associations of FSS with depressive and anxiety symptoms. In addition to enhancing FSS, PC development could be included in the prevention and treatment strategies for depressive and anxiety symptoms targeted at PLWHA employed full-time.
Cannabis use and involuntary admission may mediate long-term adherence in first-episode psychosis patients: a prospective longitudinal study
Authors: Barbeito Sara , Vega Patricia , Ruiz de Azúa Sonia , Saenz Margarita , Martinez-Cengotitabengoa Mónica , González-Ortega Itxaso , Bermudez Cristina , Hernanz Margarita , Corres Blanca Fernández de , González-Pinto Ana
Published: December 2013

Background

This study aimed to examine factors associated with treatment adherence in first-episode psychosis (FEP) patients followed up over 8 years, especially involuntary first admission and stopping cannabis use.

Methods

This prospective, longitudinal study of FEP patients collected data on symptoms, adherence, functioning, and substance use. Adherence to treatment was the main outcome variable and was categorized as ‘good’ or ‘bad’. Cannabis use during follow-up was stratified as continued use, stopped use, and never used. Bivariate and logistic regression models identified factors significantly associated with adherence and changes in adherence over the 8-year follow-up period.

Results

Of the 98 FEP patients analyzed at baseline, 57.1% had involuntary first admission, 74.4% bad adherence, and 52% cannabis use. Good adherence at baseline was associated with Global Assessment of Functioning score (p = 0.019), Hamilton Depression Rating Scale score (p = 0.017) and voluntary admission (p < 0.001). Adherence patterns over 8 years included: 43.4% patients always bad, 26.1% always good, 25% improved from bad to good. Among the improved adherence group, 95.7% had involuntary first admission and 38.9% stopped cannabis use. In the subgroup of patients with bad adherence at baseline, involuntary first admission and quitting cannabis use during follow up were associated with improved adherence.

Conclusions

The long-term association between treatment adherence and type of first admission and cannabis use in FEP patients suggest targets for intervention to improve clinical outcomes.
Correlates of consistent condom use among men who have sex with men recruited through the Internet in Huzhou city: a cross-sectional survey
Authors: Jin Meihua , Yang Zhongrong , Dong Zhengquan , Han Jiankang
Published: December 2013

Background

There is growing evidence that men who have sex with men (MSM) are currently a group at high risk of HIV infection in China. Our study aims to know the factors affecting consistent condom use among MSM recruited through the internet in Huzhou city.

Methods

An anonymous cross-sectional study was conducted by recruiting 410 MSM living in Huzhou city via the Internet. The socio-demographic profiles (age, education level, employment status, etc.) and sexual risk behaviors of the respondents were investigated. Bivariate logistic regression analyses were performed to compare the differences between consistent condom users and inconsistent condom users. Variables with significant bivariate between groups’ differences were used as candidate variables in a stepwise multivariate logistic regression model. All statistical analyses were performed using SPSS for Windows 17.0, and a p value < 0.05 was considered to be statistically significant.

Results

According to their condom use, sixty-eight respondents were classified into two groups. One is consistent condom users, and the other is inconsistent condom users. Multivariate logistic regression showed that respondents who had a comprehensive knowledge of HIV (OR = 4.08, 95% CI: 1.85-8.99), who had sex with male sex workers (OR = 15.30, 95% CI: 5.89-39.75) and who had not drunk alcohol before sex (OR = 3.10, 95% CI: 1.38-6.95) were more likely to be consistent condom users.

Conclusions

Consistent condom use among MSM was associated with comprehensive knowledge of HIV and a lack of alcohol use before sexual contact. As a result, reducing alcohol consumption and enhancing education regarding the risks of HIV among sexually active MSM would be effective in preventing of HIV transmission.
Empowerment, partner’s behaviours and intimate partner physical violence among married women in Uganda
Authors: Kwagala Betty , Wandera Stephen Ojiambo , Ndugga Patricia , Kabagenyi Allen
Published: December 2013

Background

There is dearth of knowledge and research about the role of empowerment, partners’ behaviours and intimate partner physical violence (IPPV) among married women in Uganda. This paper examined the influence of women’s empowerment and partners’ behaviours on IPPV among married women in Uganda.

Methods

The 2011 Uganda Demographic and Health Survey data were used, selecting a weighted sample of 1,307 women in union considered for the domestic violence module. Cross tabulations (chi-square tests) and multivariate logistic regressions were used to identify factors associated with IPPV.

Results

The prevalence of IPPV among women in union in Uganda is still high (41%). Women’s occupation was the only measure of empowerment that was significantly associated with IPPV, where women in professional employment were less likely to experience IPPV. Women from wealthy households were less likely to experience IPPV. IPPV was more likely to be reported by women who had ever had children and witnessed parental IPPV. IPPV was also more likely to be reported by women whose husbands or partners: accused them of unfaithfulness, did not permit them to meet female friends, insisted on knowing their whereabouts and sometimes or often got drunk. Women who were afraid their partners were also more likely to report IPPV.

Conclusion

In the Ugandan context, women’s empowerment as assessed by the UDHS has limited mitigating effect on IPPV in the face of partners’ negative behaviours and history of witnessing parental violence.
Risk factors for musculoskeletal pain amongst nurses in Estonia: a cross-sectional study
Authors: Freimann Tiina , Coggon David , Merisalu Eda , Animägi Liina , Pääsuke Mati
Published: December 2013

Background

Routine statistics indicate a high frequency of work-related musculoskeletal disorders in Estonia. We aimed to describe the prevalence of musculoskeletal pain (MSP) amongst Estonian nurses, and to explore associations with personal characteristics and occupational risk factors.

Methods

As a part of an international investigation (the Cultural and Psychosocial Influences on Disability (CUPID) study), a cross-sectional survey was carried out amongst registered nurses at Tartu University Hospital, focusing on pain at six anatomical sites (low back, neck, shoulder, elbow, wrist/hand and knee) lasting for more than a day during the past year and past month. Associations with regional and multi-site (≥2 anatomical sites) pain were analysed by logistic regression.

Results

Analysis was based on 221 female nurses (response rate 57%). The overall prevalence of MSP was 84% in the past year and 69% in the past month. The prevalence of multi-site pain was 60% in the past year and 40% in the past month. Low back, neck and knee were the sites most commonly painful. Pain in the past year tended to be more frequent at older ages, and with higher emotional exhaustion, and at most sites, with poor self-rated health, and reported distress from somatic symptoms. Multi-site pain was also significantly associated with older age and tendency to somatise.

Conclusions

The prevalence of MSP among Estonian nurses is high. Psychological risk factors such as somatising tendency have an important impact. However, none of the risk factors examined seems likely to explain the high frequency of work-related musculoskeletal disorders in Estonia.