bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunotherapeutic strategies to prevent and treat human herpesvirus 6 reactivation after allogeneic stem cell transplantation
Authors: Gerdemann Ulrike , Keukens Laura , Keirnan Jacqueline M. , Katari Usha L. , Nguyen Chinh T. Q. , de Pagter Anne P. , Ramos Carlos A. , Kennedy-Nasser Alana , Gottschalk Stephen M. , Heslop Helen E. , Brenner Malcolm K. , Rooney Cliona M. , Leen Ann M.
Published: November 2012

Human herpesvirus (HHV) 6 causes substantial morbidity and mortality in the immunocompromised host and has no approved therapy. Adoptive transfer of virus specific T cells has proven safe and apparently effective as prophylaxis and treatment of other virus infections in immunocompromised patients; however, extension to subjects with HHV6 has been hindered by the paucity of information on targets of cellular immunity. We now characterize the cellular immune response from 20 donors against 5 major HHV6B antigens predicted to be immunogenic and define a hierarchy of immunodominance of antigens based on the frequency of responding donors and the magnitude of the T-cell response. We identified specific epitopes within these antigens and expanded the HHV6 reactive T cells using a GMP-compliant protocol. The expanded population comprised both CD4+ and CD8+ T cells that were able to produce multiple effector cytokines and kill both peptide-loaded and HHV6B wild-type virus-infected target cells. Thus, we conclude that adoptive T-cell immunotherapy for HHV6 is a practical objective and that the peptide and epitope tools we describe will allow such cells to be prepared, administered, and monitored in human subjects.
DNA methylation changes are a late event in acute promyelocytic leukemia and coincide with loss of transcription factor binding
Authors: Schoofs Till , Rohde Christian , Hebestreit Katja , Klein Hans-Ulrich , Göllner Stefanie , Schulze Isabell , Lerdrup Mads , Dietrich Nikolaj , Agrawal-Singh Shuchi , Witten Anika , Stoll Monika , Lengfelder Eva , Hofmann Wolf-Karsten , Schlenke Peter , Büchner Thomas , Hansen Klaus , Berdel Wolfgang E. , Rosenbauer Frank , Dugas Martin , Müller-Tidow Carsten
Published: November 2012

The origin of aberrant DNA methylation in cancer remains largely unknown. In the present study, we elucidated the DNA methylome in primary acute promyelocytic leukemia (APL) and the role of promyelocytic leukemia–retinoic acid receptor α (PML-RARα) in establishing these patterns. Cells from APL patients showed increased genome-wide DNA methylation with higher variability than healthy CD34+ cells, promyelocytes, and remission BM cells. A core set of differentially methylated regions in APL was identified. Age at diagnosis, Sanz score, and Flt3-mutation status characterized methylation subtypes. Transcription factor–binding sites (eg, the c-myc–binding sites) were associated with low methylation. However, SUZ12- and REST-binding sites identified in embryonic stem cells were preferentially DNA hypermethylated in APL cells. Unexpectedly, PML-RARα–binding sites were also protected from aberrant DNA methylation in APL cells. Consistent with this, myeloid cells from preleukemic PML-RARα knock-in mice did not show altered DNA methylation and the expression of PML-RARα in hematopoietic progenitor cells prevented differentiation without affecting DNA methylation. Treatment of APL blasts with all-trans retinoic acid also did not result in immediate DNA methylation changes. The results of the present study suggest that aberrant DNA methylation is associated with leukemia phenotype but is not required for PML-RARα–mediated initiation of leukemogenesis.
Early T-cell progenitors are the major granulocyte precursors in the adult mouse thymus
Authors: De Obaldia Maria Elena , Bell J. Jeremiah , Bhandoola Avinash
Published: November 2012

The mouse thymus supports T-cell development, but also contains non–T-cell lineages such as dendritic cells, macrophages, and granulocytes that are necessary for T-cell repertoire selection and apoptotic thymocyte clearance. Early thymic progenitors (ETPs) are not committed to the T-cell lineage, as demonstrated by both in vitro and in vivo assays. Whether ETPs realize non–T-cell lineage potentials in vivo is not well understood and indeed is controversial. In the present study, we investigated whether ETPs are the major precursors of any non–T-lineage cells in the thymus. We analyzed the development of these populations under experimental circumstances in which ETPs are nearly absent due to either abrogated thymic settling or inhibition of early thymic development by genetic ablation of IL-7 receptorα or Hes1. Results obtained using multiple in vivo approaches indicate that the majority of thymic granulocytes derive from ETPs. These data indicate that myelolymphoid progenitors settle the thymus and thus clarify the pathways by which stem cells give rise to downstream blood cell lineages.
Expression of KCNQ1OT1, CDKN1C, H19, and PLAGL1 and the methylation patterns at the KvDMR1 and H19/IGF2 imprinting control regions is conserved between human and bovine
Authors: Robbins Katherine Marie , Chen Zhiyuan , Wells Kevin Dale , Rivera Rocío Melissa
Published: November 2012

Background

Beckwith-Wiedemann syndrome (BWS) is a loss-of-imprinting pediatric overgrowth syndrome. The primary features of BWS include macrosomia, macroglossia, and abdominal wall defects. Secondary features that are frequently observed in BWS patients are hypoglycemia, nevus flammeus, polyhydramnios, visceromegaly, hemihyperplasia, cardiac malformations, and difficulty breathing. BWS is speculated to occur primarily as the result of the misregulation of imprinted genes associated with two clusters on chromosome 11p15.5, namely the KvDMR1 and H19/IGF2. A similar overgrowth phenotype is observed in bovine and ovine as a result of embryo culture. In ruminants this syndrome is known as large offspring syndrome (LOS). The phenotypes associated with LOS are increased birth weight, visceromegaly, skeletal defects, hypoglycemia, polyhydramnios, and breathing difficulties. Even though phenotypic similarities exist between the two syndromes, whether the two syndromes are epigenetically similar is unknown. In this study we use control Bos taurus indicus X Bos taurus taurus F1 hybrid bovine concepti to characterize baseline imprinted gene expression and DNA methylation status of imprinted domains known to be misregulated in BWS. This work is intended to be the first step in a series of experiments aimed at determining if LOS will serve as an appropriate animal model to study BWS.

Results

The use of F1 B. t. indicus x B. t. taurus tissues provided us with a tool to unequivocally determine imprinted status of the regions of interest in our study. We found that imprinting is conserved between the bovine and human in imprinted genes known to be associated with BWS. KCNQ1OT1 and PLAGL1 were paternally-expressed while CDKN1C and H19 were maternally-expressed in B. t. indicus x B. t. taurus F1 concepti. We also show that in bovids, differential methylation exists at the KvDMR1 and H19/IGF2 ICRs.

Conclusions

Based on these findings we conclude that the imprinted gene expression of KCNQ1OT1, CDKN1C, H19, and PLAGL1 and the methylation patterns at the KvDMR1 and H19/IGF2 ICRs are conserved between human and bovine. Future work will determine if LOS is associated with misregulation at these imprinted loci, similarly to what has been observed for BWS.
First survey and functional annotation of prohormone and convertase genes in the pig
Authors: Porter Kenneth I , Southey Bruce R , Sweedler Jonathan V , Rodriguez-Zas Sandra L
Published: November 2012

Background

The pig is a biomedical model to study human and livestock traits. Many of these traits are controlled by neuropeptides that result from the cleavage of prohormones by prohormone convertases. Only 45 prohormones have been confirmed in the pig. Sequence homology can be ineffective to annotate prohormone genes in sequenced species like the pig due to the multifactorial nature of the prohormone processing. The goal of this study is to undertake the first complete survey of prohormone and prohormone convertases genes in the pig genome. These genes were functionally annotated based on 35 gene expression microarray experiments. The cleavage sites of prohormone sequences into potentially active neuropeptides were predicted.

Results

We identified 95 unique prohormone genes, 2 alternative calcitonin-related sequences, 8 prohormone convertases and 1 cleavage facilitator in the pig genome 10.2 assembly and trace archives. Of these, 11 pig prohormone genes have not been reported in the UniProt, UniGene or Gene databases. These genes areintermedin,cortistatin,insulin-like 5,orexigenic neuropeptide QRFP,prokineticin 2,prolactin-releasing peptide,parathyroid hormone 2,urocortin,urocortin 2,urocortin 3, andurotensin 2-related peptide. In addition, a novelneuropeptide Swas identified in the pig genome correcting the previously reported pig sequence that is identical to the rabbit sequence. Most differentially expressed prohormone genes were under-expressed in pigs experiencing immune challenge relative to the un-challenged controls, in non-pregnant relative to pregnant sows, in old relative to young embryos, and in non-neural relative to neural tissues. The cleavage prediction based on human sequences had the best performance with a correct classification rate of cleaved and non-cleaved sites of 92% suggesting that the processing of prohormones in pigs is similar to humans. The cleavage prediction models did not find conclusive evidence supporting the production of the bioactive neuropeptidesurocortin 2,urocortin 3,torsin family 2 member A,tachykinin 4,islet amyloid polypeptide, andcalcitonin receptor-stimulating peptide2 in the pig.

Conclusions

The present genomic and functional characterization supports the use of the pig as an effective animal model to gain a deeper understanding of prohormones, prohormone convertases and neuropeptides in biomedical and agricultural research.
A histone arginine methylation localizes to nucleosomes in satellite II and III DNA sequences in the human genome
Authors: Capurso Daniel , Xiong Hao , Segal Mark R
Published: November 2012

Background

Applying supervised learning/classification techniques to epigenomic data may reveal properties that differentiate histone modifications. Previous analyses sought to classify nucleosomes containing histone H2A/H4 arginine 3 symmetric dimethylation (H2A/H4R3me2s) or H2A.Z using human CD4+ T-cell chromatin immunoprecipitation sequencing (ChIP-Seq) data. However, these efforts only achieved modest accuracy with limited biological interpretation. Here, we investigate the impact of using appropriate data pre-processing —deduplication, normalization, and position- (peak-) finding to identify stable nucleosome positions — in conjunction with advanced classification algorithms, notably discriminatory motif feature selection and random forests. Performance assessments are based on accuracy and interpretative yield.

Results

We achieved dramatically improved accuracy using histone modification features (99.0%; previous attempts, 68.3%) and DNA sequence features (94.1%; previous attempts, <60%). Furthermore, the algorithms elicited interpretable features that withstand permutation testing, including: the histone modifications H4K20me3 and H3K9me3, which are components of heterochromatin; and the motif TCCATT, which is part of the consensus sequence of satellite II and III DNA. Downstream analysis demonstrates that satellite II and III DNA in the human genome is occupied by stable nucleosomes containing H2A/H4R3me2s, H4K20me3, and/or H3K9me3, but not 18 other histone methylations. These results are consistent with the recent biochemical finding that H4R3me2s provides a binding site for the DNA methyltransferase (Dnmt3a) that methylates satellite II and III DNA.

Conclusions

Classification algorithms applied to appropriately pre-processed ChIP-Seq data can accurately discriminate between histone modifications. Algorithms that facilitate interpretation, such as discriminatory motif feature selection, have the added potential to impart information about underlying biological mechanism.
Isolimonic acid interferes with Escherichia coli O157:H7 biofilm and TTSS in QseBC and QseA dependent fashion
Authors: Vikram Amit , Jesudhasan Palmy R , Pillai Suresh D , Patil Bhimanagouda S
Published: November 2012

Background

E. coli O157:H7 (EHEC) is an important human pathogen. The antibiotic treatment of EHEC reportedly results in release of Shiga toxin and is therefore discouraged. Consequently, alternative preventive or therapeutic strategies for EHEC are required. The objective of the current study was to investigate the effect of citrus limonoids on cell-cell signaling, biofilm formation and type III secretion system in EHEC.

Results

Isolimonic acid and ichangin were the most potent inhibitors of EHEC biofilm (IC25=19.7 and 28.3 μM, respectively) and adhesion to Caco-2 cells. The qPCR analysis revealed that isolimonic acid and ichangin repressed LEE encoded genes by ≈3 to 12 fold. In addition, flhDC was repressed by the two limonoids (≈3 to 7 fold). Further studies suggested that isolimonic acid interferes with AI-3/epinephrine activated cell-cell signaling pathway. Loss of biofilm inhibitory activity of isolimonic acid in ΔqseBC mutant, which could be restored upon complementation, suggested a dependence on functional QseBC. Additionally, overexpression of qseBC in wild type EHEC abated the inhibitory effect of isolimonic acid. Furthermore, the isolimonic acid failed to differentially regulate ler in ΔqseA mutant, while plasmid borne expression of qseA in ΔqseA background restored the repressive effect of isolimonic acid.

Conclusions

Altogether, results of study seem to suggest that isolimonic acid and ichangin are potent inhibitors of EHEC biofilm and TTSS. Furthermore, isolimonic acid appears to interfere with AI-3/epinephrine pathway in QseBC and QseA dependent fashion.
Prevalence and risk factors of gastroesophageal reflux symptoms in a Chinese retiree cohort
Authors: Chen Tiantian , Lu Ming , Wang Xiaofeng , Yang Yajun , Zhang Juan , Jin Li , Ye Weimin
Published: November 2012

Background

Data about prevalence of gastroesophageal reflux diseases (GERD) from Asian populations are still scarce. To provide additional data on prevalence of GERD and investigate its potential risk factors, we performed this cross-sectional study in the Taizhou Retiree Cohort.

Methods

After physical examination, the participants were asked whether they suffered with heartburn or acid regurgitation in the last 12 months by trained interviewers, and if yes, the severity and frequency of the symptoms were recorded. Odds ratios (ORs) with 95% confidence intervals (CIs) for the associations of obesity and other risk factors with GERD were derived from logistic regression models.

Results

8831 retirees completed the questionnaire and physical examination. In total 150 (1.7%) reported the symptoms occurring at least once per week within the last 12 months before the interview. Compared with subjects without GERD, having a history of diabetes mellitus (OR 2.2, 95% CI 1.4-3.5), hypertension (OR 1.4, 95% CI 1.0-2.1), gastritis (OR 8.2, 95% CI 5.8-11.5), peptic ulcer (OR 3.3, 95% CI 1.8-6.1) and high triglyceride level (≥1.81mmol/L) (OR 2.0, 95% CI 1.2-3.4) were associated with a significantly increased risk of GERD. However, there was no significant association between body mass index, waist-to-hip ratio or waist alone, smoking, consumption of alcohol & tea, and the occurrence of reflux symptoms.

Conclusions

Compared with Western populations, the prevalence of GERD in this Chinese retiree cohort is low. A history of diabetes mellitus, hypertension, gastritis, peptic ulcer or hypertriglyceridaemia increases GERD risk in this population.
Abdominal aortic aneurysm in patients affected by intermittent claudication: prevalence and clinical predictors
Authors: Giugliano Giuseppe , Laurenzano Eugenio , Rengo Carlo , De Rosa Giovanna , Brevetti Linda , Sannino Anna , Perrino Cinzia , Chiariotti Lorenzo , Schiattarella Gabriele Giacomo , Serino Federica , Ferrone Marco , Scudiero Fernando , Carbone Andreina , Sorropago Antonio , Amato Bruno , Trimarco Bruno , Esposito Giovanni
Published: November 2012

Background

Abdominal aortic aneurysm (AAA) is a frequent cause of death among elderly. Patients affected by lower extremity peripheral arterial disease (LE-PAD) seem to be particularly at high risk for AAA. We aimed this study at assessing the prevalence and the clinical predictors of the presence of AAA in a homogeneous cohort of LE-PAD patients affected by intermittent claudication.

Methods

We performed an abdominal ultrasound in 213 consecutive patients with documented LE-PAD (ankle/brachial index ≤0.90) attending our outpatient clinic for intermittent claudication. For each patient we registered cardiovascular risk factors and comorbidities, and measured neutrophil count.

Results

The ultrasound was inconclusive in 3 patients (1.4%), thus 210 patients (169 males, 41 females, mean age 65.9 ± 9.8 yr) entered the study. Overall, AAA was present in 19 patients (9.0%), with a not significant higher prevalence in men than in women (10.1% vs 4.9%, p = 0.300). Patients with AAA were older (71.2 ± 7.0 vs 65.4 ± 9.9 years, p = 0.015), were more likely to have hypertension (94.7% vs 71.2%, p = 0.027), and greater neutrophil count (5.5 [4.5 – 6.2] vs 4.1 [3.2 – 5.5] x103/μL, p = 0.010). Importantly, the c-statistic for neutrophil count (0.73, 95% CI 0.60 – 0.86, p =0.010) was higher than that for age (0.67, CI 0.56–0.78, p = 0.017). The prevalence of AAA in claudicant patients with a neutrophil count ≥ 5.1 x103/μL (cut-off identified at ROC analysis) was as high as 29.0%.

Conclusions

Prevalence of AAA in claudicant patients is much higher than that reported in the general population. Ultrasound screening should be considered in these patients, especially in those with an elevated neutrophil count.
Endovascular treatment of lower extremity arteries is associated with an improved outcome in diabetic patients affected by intermittent claudication
Authors: Giugliano Giuseppe , Perrino Cinzia , Schiano Vittorio , Brevetti Linda , Sannino Anna , Schiattarella Gabriele Giacomo , Gargiulo Giuseppe , Serino Federica , Ferrone Marco , Scudiero Fernando , Carbone Andreina , Bruno Antonio , Amato Bruno , Trimarco Bruno , Esposito Giovanni
Published: November 2012

Background

Lower extremity peripheral arterial disease (LE-PAD) is a highly prevalent condition among diabetic patients, associated with reduced walking capacity and a high incidence of cardiovascular events. Endovascular revascularization of lower extremities arteries improves walking performance and quality of life of diabetic patients affected by intermittent claudication, but few studies evaluated the impact of revascularization on cardiovascular outcome in this high-risk population. Accordingly, in the present study we evaluated if leg-ischemia resolution by effective lower limbs percutaneous revascularization can also impact cardiovascular outcome in a homogeneous group of diabetic patients affected by intermittent claudication.

Methods

236 diabetic patients affected by LE-PAD at stage II of Fontaine’s classification, with ankle/brachial index ≤0.90 and one or more hemodynamically significant stenosis in at least one artery of the ileo-femoro-popliteal axis were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 123 (52.1%) underwent percutaneous transluminal angioplasty (PTA group), while 113 (47.9%) underwent conservative medical therapy only (MT group). The incidence of major cardiovascular events (cardiovascular death, myocardial infarction, ischemic stroke, coronary or carotid revascularization) was prospectively analyzed with Kaplan-Meier curves and the risk of developing a cardiovascular event calculated by Cox analyses.

Results

No baseline difference in cardiovascular risk factors were observed between the PTA and MT groups, except for a lower prevalence of males in PTA group (74.8% vs. 85.8%, p=0.034). Furthermore, patients in the PTA group showed a worse walking capacity as expressed by maximum walking distance (108.7 ± 300.9 vs 378.4 ± 552.3 meters, p<0.001). During a median follow-up of 20 months (12.0-29.0), the incidence of cardiovascular events was markedly lower in patients in the PTA group with respect to patients in the MT group (7.3% vs. 22.1%, p=0.001), and patients of the MT group had at Cox analysis a 3.9 increased risk with respect to PTA group, after adjustment for potential confounding factors (95% CI 1.1-15.3, p=0.049).

Conclusions

The present study shows that lower limbs revascularization of diabetic patients affected by intermittent claudication, in addition to improve walking performance, is associated with a reduction in the incidence of future major cardiovascular events.
Major postoperative complications and survival for colon cancer elderly patients
Authors: Grosso Giuseppe , Biondi Antonio , Marventano Stefano , Mistretta Antonio , Calabrese Giorgio , Basile Francesco
Published: November 2012

Background

Increased life expectancy has led to elevating the mean age of the patients at the time of diagnosis of colon cancer and subsequent treatment. Differences in complication rates and outcome between elderly and younger patients have been investigated.

Methods

We retrospectively analysed a database containing the information of patients who underwent surgery for stage I-III colorectal cancer from January 2004 to January 2012 at our institution and compared demographic, cancer-related, and outcomes data of 235 elderly patients with 211 patients ≤65 years old.

Results

Intraoperative complications did not differ between young and old patients whereas some differences have been found in postoperative and late complications: elderly patients suffered more by ileus (P = 0.024), peritonitis or septic shock (P = 0.017), pelvic abscess (P = 0.028), wound infection (P = 0.031), and incisional/port herniation (P = 0.012) compared with younger patients. Moreover, elderly patients suffered by systemic complications such as cardiovascular (4.7% vs. 1.4%, P = 0.049), renal (4.7% vs. 0.5%, P = 0.006), and respiratory (10.6% vs. 5.2%, P = 0.036). The multivariate analysis assessing the odds of having a complication revealed that older age (Odd Ratio [OR] 2.75, 95% Confidential Interval [CI]: 1.67-4.52) and open surgery (OR 1.63, 95% CI: 1.01-2.62) are significantly and independently associated with having a complication.

Conclusions

In our series, elderly patients have presented a slight higher incidence of comorbidities that may affect the incidence rates of postoperative complications. These results have implications in increasing the hospital stay as well as a higher rate of death.
Sexual asthenia: Tradamixina versus Tadalafil 5 mg daily
Authors: Iacono Fabrizio , Prezioso Domenico , Illiano Ester , Romeo Giuseppe , Ruffo Antonio , Amato Bruno
Published: November 2012

Background

Reduced libido is widely considered the most prominent symptomatic reflection of low testosterone (T) levels in men. Testosterone deficiency (TD) afflicts approximately 30% of men aged 40-79 years. This study seeks to evaluate the effect of a new natural compound “tradamixina “in order to improve male sexual function in elderly men, particularly libido and possible erectile dysfunction, versus administration of tadalafil 5 mg daily.

Methods

Seventy patients (67.3± 3.7 years) with stable marital relations and affected by reduced libido, with or without erectile dysfunction were recruited. They were randomly separated in 2 groups A-B of 35. Group A was administered twice a day a new compound “Tradamixina” (150 mg of Alga Ecklonia Bicyclis, 396 mg of Tribulus Terrestris and 144 mg of D-Glucosamine and N-Acetyl-D-Glucosamine) for two months, while Group B was administered tadalafil 5 mg daily, for two months. At visit and after 60 days of treatment patients were evaluated by means of detailed medical and sexual history, clinical examination, laboratory investigations (Total and Free T), instrumental examination (NPTR- nocturnal penile tumescence and rigidity test- with Rigiscan). Patients completed a self-administered IIEF questionnaire (The international index of erectile function) and SQoLM questionnaire (Sexual quality of life Questionnarie-Male). The results pre and post treatment were compared by Student t test (p<0.005).

Results

After 2 months of treatment in group A serum TT levels (230±18 ng/dl vs 671±14 ng/dl ) and FT levels(56± 2.4 pg/ml vs 120± 3.9pg/ml) increased, while in group B serum TT levels (245±12 ng/dl vs 247±15 ng/dl ) and FT levels(53± 0.3 pg/ml vs 55± 0.5pg/ml) increased not statistically significant. The patient’s numbers with negative NPTR improved after treatment in group A and B (15 vs 18 and 13 vs 25 respectively). The IIEF total score in group A increased after treatment with tradamixina (15±1.5 vs 29.77±1.2); the IIEF total score in group B increased slightly (12±1.3 vs 23.40±1.2). The SQoLM total score improved in both groups (A:16±2,3 vs 33±4,1 and B: 16±3,4 vs 31±2,1).

Conclusion

The treatment twice a day with “Tradamixina” for 2 months improved libido in elderly men without side effects of Tadalafil.
Treatment of a rapidly expanding thoracoabdominal aortic aneurysm after endovascular repair of descending thoracic aortic aneurysm in an old patient
Authors: Mannacio Vito , Mottola Michele , Ruggiero Danilo , D’Alessio Andrea , Surace Giuseppina Gabriella , Di Tommaso Ettorino , Amato Bruno , Iannelli Gabriele
Published: November 2012

Background

Aortic pathology progression and/or procedure related complications following endovascular repair should always be considered mostly in older patients. We herein describe a hybrid procedure for treatment of rapidly expanding thoracoabdominal aneurysm following endovascular treatment of a descending thoracic aortic aneurysm in an older patient.

Case presentation

A 82-year-old man at 18 months after endovascular surgery for a contained rupture of descending thoracic aortic aneurysm revealed a type IV thoracoabdominal aneurysm with significant increase of the aortic diameters at superior mesenteric and renal artery levels. A hybrid approach consisting of preventive visceral vessel revascularization and endovascular repair of entire abdominal aorta was performed. Under general anaesthesia and by xyphopubic laparotomy, the infrarenal aneurysmatic aorta and common iliac arteries were replaced by a bifurcated woven prosthetic graf. From each of the prosthetic branches two reverse 14x7 mm bifurcated PTFE prosthetic grafts were anastomized to both renal arteries and to the celiac axis and superior mesenteric artery, respectively. Vessel ischemia was restricted to the time required for anastomosis. Three 10 cm Gore endovascular stent-grafts for a total length of 15 cm, were used. The overlapping of the stent-grafts was carried out from the bottom upwards, starting from the aorto-iliac prosthetic body up to the healthy segment of thoracic aorta, 40 mm from the previous stent-grafts.

The patient was discharged on the 9th postoperative day.

Conclusion

This technique offers the advantage of a less invasive treatment, reducing the risk of paraplegia, visceral ischaemia and pulmonary complications, mostly in older patients.
Surgery for a gastric Dieulafoy’s lesion reveals an occult bleeding jejunal diverticulum. A case report
Authors: Orlando G , Luppino IM , Gervasi R , Lerose MA , Amato B , Spagnuolo R , Marasco R , Doldo P , Puzziello A
Published: November 2012

Background

Jejunal diverticulosis is an uncommon disease and usually asymptomatic. It can be complicated not only by diverticulitis, but by hemorrhage, perforation, intussusception, volvulus, malabsorption and even small bowel obstruction due to enteroliths formed and expelled from these diverticula.

Methods

We describe a case of an occult bleeding jejunal diverticulum, casually discovered in a patient that was taken to surgery for a Dieulafoy’s lesion after unsuccessful endoscopic treatment. We performed a gastric resection together with an ileocecal resection.

Macroscopic and microscopic examinations confirmed the gastric Dieulafoy’s lesion and demonstrated the presence of another source of occult bleeding in asymptomatic jejunal diverticulum.

Discussion

The current case emphasizes that some gastrointestinal bleeding lesions, although rare, can be multiple and result in potentially life-threatening bleeding. The clinician must be mindful to the possibility of multisite lesions and to the correlation between results of the investigations and clinical condition of the bleeding patient.
Feasibility of capsule endoscopy in elderly patients with obscure gastrointestinal bleeding. An up-to-date report
Authors: Orlando G , Luppino IM , Lerose MA , Gervasi R , Amato B , Silecchia G , Puzziello A
Published: November 2012

Background

Anemia is the most common hematologic abnormality in older populations. Furthermore, iron deficiency anemia is common and merits investigation and treatment, as it usually results from chronic occult bleeding from the gastrointestinal tract. In view of a wide use of capsule endoscopy as a diagnostic procedure for occult gastrointestinal bleeding and of the growth of aging population, we performed a literature review about the feasibility of capsule endoscopy in the elderly.

Methods

We conducted a literature search in the PubMed database in July 2012, and all English-language publications on capsule endoscopy in elderly patients since 2005 were retrieved. The potential original articles mainly focused on obscure gastrointestinal bleeding were all identified and full texts were obtained and reviewed for further hand data retrieving.

Results

We retrieved only six papers based on different primary end-points. Four were retrospective non randomized studies and two were prospective non randomized studies. In the end 65, 70, 80 and 85 years were used as an age cut-off. All studies evaluate the diagnostic yield of capsule endoscopy in iron deficiency anemia. Only three studies assess the feasibility of capsule examination of the elderly.

Conclusions

Iron deficiency anemia in the elderly with or without obscure gastrointestinal bleeding is the major indication for capsule endoscopy after a negative esophago-gastro-duodenoscopy and colonoscopy. It is safe and effective to identify a small bowel pathology without a great discomfort for the elderly. Inability to swallow the capsule, battery failure before capsule reaches the cecum, and capsule retention are some of the important problems associated with capsule endoscopy in elderly as well as in younger patients.
Association between 24-hour urine sodium and potassium excretion and diet quality in six-year-old children: a cross sectional study
Authors: Kristbjornsdottir Oddny K , Halldorsson Thorhallur I , Thorsdottir Inga , Gunnarsdottir Ingibjorg
Published: November 2012

Background

Limited data is available on sodium (Na) and potassium (K) intake in young children estimated by 24 hour (24h) excretion in urine. The aim was to assess 24h urinary excretion of Na and K in six-year-old children and its relationship with diet quality.

Methods

The study population was a subsample of a national dietary survey, including six-year-old children living in the greater Reykjavik area (n=76). Three day weighed food records were used to estimate diet quality. Diet quality was defined as adherence to the Icelandic food based dietary guidelines. Na and K excretion was analyzed from 24h urine collections. PABA check was used to validate completeness of urine collections. The associations between Na and K excretion and diet quality were estimated by linear regression, adjusting for gender and energy intake.

Results

Valid urine collections and diet registrations were provided by 58 children. Na and K excretion was, mean (SD), 1.64 (0.54) g Na/24h (approx. 4.1 g salt/24h) and 1.22 (0.43) g K/24h. In covariate adjusted models Na excretion decreased by 0.16 g Na/24h (95% CI: 0.31, 0.06) per 1-unit increase in diet quality score (score range: 1–4) while K excretion was increased by 0.18 g K/24h (95% CI: 0.06, 0.29).

Conclusions

Na intake, estimated by 24h urinary excretion was on average higher than recommended. Increased diet quality was associated with lower Na excretion and higher K excretion in six-year-old children.
Dihydrotestosterone induces SREBP-1 expression and lipogenesis through the phosphoinositide 3-kinase/Akt pathway in HaCaT cells
Authors: Zhou Bing-rong , Huang Qiu-hong , Xu Yang , Wu Di , Yin Zhi-qiang , Luo Dan
Published: November 2012

Background

The purpose of this study was to investigate the effects and mechanisms of dihydrotestosterone (DHT)-induced expression of sterol regulatory element binding protein-1 (SREBP-1), and the synthesis and secretion of lipids, in HaCaT cells. HaCaT cells were treated with DHT and either the phosphoinositide 3-kinase inhibitor LY294002 or the extracellular-signal-regulated kinase (ERK) inhibitor PD98059. Real time-PCR, Western blot, Oil Red staining and flow cytometry were employed to examine the mRNA and protein expressions of SREBP-1, the gene transcription of lipid synthesis, and lipid secretion in HaCaT cells.

Findings

We found that DHT upregulated mRNA and protein expressions of SREBP-1. DHT also significantly upregulated the transcription of lipid synthesis-related genes and increased lipid secretion, which can be inhibited by the addition of LY294002.

Conclusions

Collectively, these results indicate that DHT induces SREBP-1 expression and lipogenesis in HaCaT cells via activation of the phosphoinositide 3-kinase/Akt Pathway.
Composition of fatty acids in the maternal and umbilical cord plasma of adolescent and adult mothers: relationship with anthropometric parameters of newborn
Authors: Oliveira Olívia RC , Santana Michelle G , Santos Flávia S , Conceição Felipe D , Sardinha Fátima LC , Veiga Glória V , Tavares do Carmo Maria G
Published: November 2012

Background

Considering the importance of long chain polyunsaturated fatty acids to fetal development and the lack of studies that have compared the status of fatty acids between adolescents and adults mothers, the purpose of this study was to evaluate the composition of fatty acids in maternal and umbilical cord plasma from adolescent and adults mothers.

Methods

Forty pregnant adolescents and forty pregnant adults were selected to assess the distribution profile of fatty acids in the maternal and umbilical cord plasma. Quantification of fatty acids in the total lipids of the sample groups was performed through the use of gas-liquid chromatography.

Results

The maternal and umbilical cord plasma of the adolescents showed a greater concentration of AA than did that of the adults (P < 0.05). However, a greater percentage of EPA was found in the umbilical cord plasma of the adults (P < 0.05). DHA in the plasma of the adolescent mothers correlated positively to birth weight and head circumference.

Conclusions

This suggests that in situations of greater nutritional risk, as in adolescent pregnancy, n-3PUFA concentrations have a greater influence on the proper development of newborns. Moreover, variations in fatty acid concentrations in the maternal and cord plasma of adolescents and adults may indicate that pregnancy affects the LC-PUFA status of adults and adolescents in distinct ways.
In silico vs in vitro analysis of primer specificity for the detection of Gardnerella vaginalis, Atopobium vaginae and Lactobacillus spp.
Authors: Henriques Ana , Cereija Tatiana , Machado António , Cerca Nuno
Published: November 2012

Background

Bacterial vaginosis (BV) is a common pathology of women in reproductive age that can lead to serious health complications, and is associated with shifts in the normal microflora from predominance of Lactobacillus spp. to a proliferation of other anaerobes such as G. vaginalis and A vaginae, which can be detected by PCR. The optimal PCR pathogen detection assay relies mainly on the specificity and sensitivity of the primers used.

Findings

Here we demonstrate that in silico analytical testing of primer specificity is not a synonym to in vitro analytical specificity by testing a range of published and newly designed primers with both techniques for the detection of BV-associated microorganisms.

Conclusions

By testing primer in vitro specificity with a sufficient range of bacterial strains, we were able to design primers with higher specificity and sensitivity. Also by comparing the results obtained for the newly designed primers with other previously published primers, we confirmed that in silico analysis is not sufficient to predict in vitro specificity. As such care must be taken when choosing the primers for a detection assay.
Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer
Authors: Seto Belinda
Published: November 2012

Rapamycin was discovered more than thirty years ago from a soil sample from the island of Rapa Nui. It was isolated from Streptomyces hygroscopicus and initial characterization focused on its antifungal activities. Subsequent characterization showed that it has immunosuppressive properties and has been used successfully to reduce organ rejection with kidney transplantation. Rapamycin has proven to be a versatile compound with several seemingly unrelated properties, including antifungal, immunosuppressive, and anticancer. The National Cancer Institute (NCI) Developmental Therapeutics Program demonstrated that rapamycin inhibited cell growth in tumor cell lines. These observations stimulated research to explore the underlying mechanism of anti‐tumor activities. Cell growth inhibition involves binding to the mammalian Target of Rapamycin (mTOR). The mTOR signaling pathway is critical to cell growth, proliferation, and survival and rapamycin inhibits these hallmark processes of cancer. Binding of growth factors activates mTOR signaling, which in turn leads to downstream phosphorylation of protein kinases, e.g., p70S6 kinase and lipid kinases in the phosphorylation of phosphoinositides. Understanding of mTOR signaling provided the biological basis for targeted chemotherapeutics development, including several rapamycin analogues for treating breast and other cancers.
Microbiome dynamics of human epidermis following skin barrier disruption
Authors: Zeeuwen Patrick LJM , Boekhorst Jos , van den Bogaard Ellen H , de Koning Heleen D , van de Kerkhof Peter MC , Saulnier Delphine M , van Swam Iris I , van Hijum Sacha AFT , Kleerebezem Michiel , Schalkwijk Joost , Timmerman Harro M
Published: November 2012

Background

Recent advances in sequencing technologies have enabled metagenomic analyses of many human body sites. Several studies have catalogued the composition of bacterial communities of the surface of human skin, mostly under static conditions in healthy volunteers. Skin injury will disturb the cutaneous homeostasis of the host tissue and its commensal microbiota, but the dynamics of this process have not been studied before. Here we analyzed the microbiota of the surface layer and the deeper layers of the stratum corneum of normal skin, and we investigated the dynamics of recolonization of skin microbiota following skin barrier disruption by tape stripping as a model of superficial injury.

Results

We observed gender differences in microbiota composition and showed that bacteria are not uniformly distributed in the stratum corneum. Phylogenetic distance analysis was employed to follow microbiota development during recolonization of injured skin. Surprisingly, the developing neo-microbiome at day 14 was more similar to that of the deeper stratum corneum layers than to the initial surface microbiome. In addition, we also observed variation in the host response towards superficial injury as assessed by the induction of antimicrobial protein expression in epidermal keratinocytes.

Conclusions

We suggest that the microbiome of the deeper layers, rather than that of the superficial skin layer, may be regarded as the host indigenous microbiome. Characterization of the skin microbiome under dynamic conditions, and the ensuing response of the microbial community and host tissue, will shed further light on the complex interaction between resident bacteria and epidermis.
Evidence for conserved post-transcriptional roles of unitary pseudogenes and for frequent bifunctionality of mRNAs
Authors: Marques Ana C , Tan Jennifer , Lee Sheena , Kong Lesheng , Heger Andreas , Ponting Chris P
Published: November 2012

Background

Recent reports have highlighted instances of mRNAs that, in addition to coding for protein, regulate the abundance of related transcripts by altering microRNA availability. These two mRNA roles - one mediated by RNA and the other by protein - are inter-dependent and hence cannot easily be separated. Whether the RNA-mediated role of transcripts is important, per se, or whether it is a relatively innocuous consequence of competition by different transcripts for microRNA binding remains unknown.

Results

Here we took advantage of 48 loci that encoded proteins in the earliest eutherian ancestor, but whose protein-coding capability has since been lost specifically during rodent evolution. Sixty-five percent of such loci, which we term 'unitary pseudogenes', have retained their expression in mouse and their transcripts exhibit conserved tissue expression profiles. The maintenance of these unitary pseudogenes' spatial expression profiles is associated with conservation of their microRNA response elements and these appear to preserve the post-transcriptional roles of their protein-coding ancestor. We used mouse Pbcas4, an exemplar of these transcribed unitary pseudogenes, to experimentally test our genome-wide predictions. We demonstrate that the role of Pbcas4 as a competitive endogenous RNA has been conserved and has outlived its ancestral gene's loss of protein-coding potential.

Conclusions

These results show that post-transcriptional regulation by bifunctional mRNAs can persist over long evolutionary time periods even after their protein coding ability has been lost.
Education provided to outgoing UK medical elective students regarding HIV risk and post exposure prophylaxis
Authors: Stacey K , Sellers L , Barrett S
Published: November 2012

Previous studies suggested medical schools were failing to provide sufficient support for students undertaking electives in areas with high HIV prevalence and despite updated Department of Health (DoH) guidelines, not all were advising post exposure prophylaxis (PEP) starter packs where appropriate. This study assessed whether there has been improvement in risk reduction provided by home institutions. Questionnaires were emailed to all 29 UK medical schools offering an elective. A total of 26 medical schools responded. Only one failed to offer PEP starter packs or advice on where to obtain one. Support and advice provided by the other 25 varied considerably. HIV risk education and provision of PEP to elective students has improved. A discrepancy between advice given, supervision of projects and provision of PEP starter packs across UK medical schools remains. We reiterate recommendations put forward previously that there is a need for regularly updated national guidelines published by experts, issued to all medical schools.
Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum in clinical and non-clinical settings, Arkhangelsk Oblast, Russia
Authors: Berle L M , Firsova N , Kalashnik A , Protasova V M , Ponomareva Z V , Gubernickaya S V , Kudrina T I , Haaheim H , Hjelmevoll S O , Skogen V
Published: November 2012

Russia and Eastern Europe have the fastest growing HIV epidemic in the world. As sexually transmitted infections (STIs) play an important role in HIV transmission, we conducted this study to find the prevalence of three microorganisms associated with STIs in Arkhangelsk Oblast, Russia. First void urine from 1729 participants was analysed using nucleic acid amplification testing, and all participants completed a questionnaire. One hundred and twelve (6.5%) were tested positive for Chlamydia trachomatis, 67 (3.9%) for Mycoplasma genitalium and 221 (12.8%) for Ureaplasma urealyticum. A significant association was found between C. trachomatis and U. urealyticum (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.1 to 3.0). U. urealyticum was associated with similar social demographics and sexual risks as C. trachomatis and M. genitalium. This suggests that U. urealyticum has a possible role as an STI pathogen or might be a contributing factor for the spread of other STIs.
Association between smoking and size of anal warts in HIV-infected women
Authors: Luu H N , Amirian E S , Beasley R P , Piller L , Chan W , Scheurer M E
Published: November 2012

While the association between smoking and human papillomavirus infection, cervical cancer, and anal cancer has been well studied, evidence on the association between cigarette smoking and anal warts is limited. The purpose of this study was to investigate if cigarette smoking status influences the size of anal warts over time in HIV-infected women in a sample of 976 HIV-infected women from the Women's Interagency HIV Study (WIHS). A linear mixed model was used to determine the effect of smoking on anal wart size. Even though women who were currently smokers had larger anal warts at baseline and slower growth rate of anal wart size after each visit than women who were not current smokers, there was no association between size of anal wart and current smoking status over time. Further studies on the role of smoking and interaction between smoking and other risk factors, however, should be explored.
Herpes simplex virus type 2 infection as a biomarker for sexual debut among young people in sub-Saharan Africa: a literature review
Authors: Bastien S , Mason-Jones A J , De Koker P , Mmbaga E J , Ross D A , Mathews C
Published: November 2012

Biological markers are needed in order to provide objective measures to validate self-reported sexual behaviour and interpret prevention trial data. In this review, we evaluated herpes simplex type 2 virus (HSV-2), one of the most prevalent sexually transmitted infections in sub-Saharan Africa as a biological marker of sexual debut. Based on our findings, we do not recommend using HSV-2 as a biomarker for sexual debut due to its low transmission probabilities and the fact that HSV-2 prevalence is not 100% among potential sexual partners. We recommend that the validation of alternative biological measures should be prioritized, and included in future studies and trials of interventions to reduce sexual health risk.
Association between herpes simplex virus type 2 and HIV-1 in a population of married couples from Dakar, Senegal
Authors: Camara M , Seydi M , Dieye T N , Sow P S , Mboup S , Kestens L , Jennes W
Published: November 2012

Numerous studies suggest that herpes simplex virus type 2 (HSV-2) increases the risk of HIV-1 infection but recent clinical trials of HSV-2 suppressive therapy failed to show an effect. We assessed the putative association between HSV-2 and HIV-1 in a population of HIV-concordant-negative, HIV-1-discordant and HIV-1-concordant-positive married couples from Dakar, Senegal. In agreement with previous studies, we observed a strong overall association between HSV-2 and HIV-1 (odds ratio 4.61; P < 0.001). However, this association was mainly determined by a low HSV-2 prevalence in HIV-concordant-negative couples compared with HIV-1-discordant and HIV-1-concordant-positive couples (23% versus 59% and 66%, respectively; P < 0.001). We observed no further differences in HSV-2 prevalence between HIV-1-discordant and HIV-1-concordant-positive couples (59% and 66%, respectively; P = 0.483). Neither the index (59% versus 62%, P = 1.000) nor recipient partners (41% versus 63%, P = 0.131) in HIV-1-discordant and HIV-1-concordant-positive couples showed significant differences in HSV-2 prevalence. HSV-2 does not constitute a clear risk factor for HIV-1 infection in this population.