Anaesthetic management of a parturient with an unrepaired coronary arteriovenous fistula for caesarean section.

Coronary arteriovenous fistulas are an abnormal conduit between a coronary artery and another cardiovascular lumen, without an intervening capillary bed. The reported prevalence is 0.002-0.3%. Physiologic consequences such as congestive heart failure, coronary steal phenomenon and fistula aneurysm formation and rupture are possible. There are limited reports of symptomatic coronary arteriovenous fistulas in association with pregnancy. We describe a 19-year-old woman with symptomatic left circumflex artery to coronary sinus fistula, terminating into a large exophytic varix in the right atrium, presenting for an elective caesarean section at 37 weeks gestational age. Our anaesthetic management strategy aimed to optimise myocardial perfusion, maintain euvolemia, avoid right ventricular obstruction from exophytic varix and avoid sympathetic stimulation or sudden increases in pulmonary vascular resistance. A slowly titrated epidural was used as the primary anaesthetic. Our patient tolerated the procedure well and was discharged home on postoperative day two. Understanding of the potential physiologic consequence of coronary arteriovenous fistulas, and interaction with the physiologic changes of pregnancy and delivery, are essential for the management of these cases.

A desiccated dual-species subaerial biofilm reprograms its metabolism and affects water dynamics in limestone.

Understanding the impact of sessile communities on underlying materials is of paramount importance in stone conservation. Up until now, the critical role of subaerial biofilms (SABs) whether they are protective or deteriorative remains unclear, especially under desiccation. The interest in desiccated SABs is raised by the prediction of an increase in drought events in the next decades that will affect the Mediterranean regions' rich stone heritage as never before. Thus, the main goal of this research is to study the effects of desiccation on both the biofilms' eco-physiology and its impacts on the lithic substrate. To this end, we used a dual-species model system composed of a phototroph and a chemotroph to simulate biofilm behavior on stone heritage. We found that drought altered the phototroph-chemotroph balance and enriched the biofilm matrix with proteins and DNA. Desiccated SABs underwent a shift in metabolism to fermentation and a decrease in oxidative stress. Additionally, desiccated SABs changed the water-related dynamics (adsorption, evaporation, and wetting properties) in limestone. Water absorption experiments showed that desiccated SABs protected the stone from rapid water uptake, while a thermographic survey indicated a delay in water evaporation. Spilling-drop tests revealed a change in the wettability of the stone-SAB interface, which affected the water transport properties of the stone. Finally, desiccated SABs reduced stone swelling in the presence of water vapor. The biodeteriorative and bioprotective implications of desiccated SABs on the stone were ultimately assessed.

Abnormal neovascular and proliferative conjunctival phenotype in limbal stem cell deficiency is associated with altered microRNA and gene expression modulated by PAX6 mutational status in congenital aniridia.

PURPOSE: To evaluate conjunctival cell microRNA (miRNAs) and mRNA expression in relation to observed phenotype of progressive limbal stem cell deficiency in a cohort of subjects with congenital aniridia with known genetic status. METHODS: Using impression cytology, bulbar conjunctival cells were sampled from 20 subjects with congenital aniridia and 20 age and sex-matched healthy control subjects. RNA was extracted and miRNA and mRNA analyses were performed using microarrays. Results were related to severity of keratopathy and genetic cause of aniridia. RESULTS: Of 2549 miRNAs, 21 were differentially expressed in aniridia relative to controls (fold change ≤ -1.5 or ≥ +1.5). Among these miR-204-5p, an inhibitor of corneal neovascularization, was downregulated 26.8-fold in severely vascularized corneas. At the mRNA level, 539 transcripts were differentially expressed (fold change ≤ -2 or ≥ +2), among these FOSB and FOS were upregulated 17.5 and 9.7-fold respectively, and JUN by 2.9-fold, all being components of the AP-1 transcription factor complex. Pathway analysis revealed enrichment of PI3K-Akt, MAPK, and Ras signaling pathways in aniridia. For several miRNAs and transcripts regulating retinoic acid metabolism, expression levels correlated with keratopathy severity and genetic status. CONCLUSION: Strong dysregulation of key factors at the miRNA and mRNA level suggests that the conjunctiva in aniridia is abnormally maintained in a pro-angiogenic and proliferative state, and these changes are expressed in a PAX6 mutation-dependent manner. Additionally, retinoic acid metabolism is disrupted in severe, but not mild forms of the limbal stem cell deficiency in aniridia.

A treatise on endothelial biology and exosomes: homage to Theresa Maria Listowska Whiteside.

Exosomes are the current primary research focus of Dr. Theresa L. Whiteside. They are key mediators of intercellular communication in the head and neck, as well as other sites. Their effects in the tumor microenvironment are manifold and include suppression of immunity, promotion of angiogenesis, enabling of metastasis, as well as reprogramming of fibroblasts and mesenchymal stromal cells. The aim of this communication is to summarize Dr. Whiteside's contribution to the field of exosome research and details the interactions of exosomes with endothelial cells leading to recent findings on how to target endothelial cells using exosomes as a therapeutic approach.

Limited Long-Term Impact of Insect Venom Immunotherapy on the Micro-RNA Landscape in Whole Blood.

OBJECTIVE: To perform a genome-wide characterization of changes in microRNA (miRNA) expression during the course of venom immunotherapy (VIT). METHODS: miRNA was isolated from the whole-blood of 13 allergic patients and 14 controls, who experienced no allergic reaction upon stings by honeybees and wasps. We analyzed 2549 miRNAs from the whole blood of these patients prior to VIT and 12 months after the start of VIT. The results for differential expression obtained on a microarray platform were confirmed by quantitative real-time PCR. Out of the 13 patients, 8 had a negative allergic reaction with VIT, thus indicating that this approach was successful. RESULTS: By comparing time points before and 12 months after ultrarush VIT, correlation analysis and principal component analysis both indicated a limited effect of VIT on the overall miRNA expression pattern. Volcano plot analysis based on raw P values revealed few deregulated miRNAs, most of which were increasingly expressed after VIT as compared with before VIT. Based on the 50 most altered miRNAs, no clear clustering was observed before or after VIT. CONCLUSIONS: Our results indicate an overall reduced effect of VIT on the miRNA expression pattern in whole blood.

Limited long-term impact of insect venom immunotherapy on the micro-RNA landscape in whole blood

Objective: To perform a genome-wide characterization of changes in microRNA (miRNA) expression during the course of venom immunotherapy (VIT). Methods: miRNA was isolated from the whole-blood of 13 allergic patients and 14 controls, who experienced no allergic reaction upon stings by honeybees and wasps. We analyzed 2549 miRNAs from the whole blood of these patients prior to VIT and 12 months after the start of VIT. The results for differential expression obtained on a microarray platform were confirmed by quantitative real-time PCR. Out of the 13 patients, 8 had a negative allergic reaction with VIT, thus indicating that this approach was successful. Results: By comparing time points before and 12 months after ultrarush VIT, correlation analysis and principal component analysis both indicated a limited effect of VIT on the overall miRNA expression pattern. Volcano plot analysis based on raw P values revealed few deregulated miRNAs, most of which were increasingly expressed after VIT as compared with before VIT. Based on the 50 most altered miRNAs, no clear clustering was observed before or after VIT. Conclusions: Our results indicate an overall reduced effect of VIT on the miRNA expression pattern in whole blood

Objetivo: Realizar la caracterización genómica de los cambios en la expresión de microARN (miARN) en el curso de ITV (inmunoterapia con veneno). Métodos: Los microARNs se analizaron en la sangre total de 13 pacientes alérgicos y 14 controles sin reacción alérgica a las picaduras de abejas y avispas. Se analizaron 2549 miRNAs diferentes en la sangre total de estos pacientes antes de la ITV y 12 meses después del inicio de la ITV. Los resultados de expresión diferencial obtenidos en la plataforma de microarrays se confirmaron mediante PCR cuantitativa a tiempo real (qRT-PCR). De los 13 pacientes, se confirmó que ocho tenían una reacción alérgica negativa tras la ITV, lo que indicó una ITV exitosa. Resultados: Al comparar los resultados de microRNAs, previa IT y 12 meses después de la ITV, la correlación y el análisis de componentes principales indican un efecto limitado de la ITV en el patrón de expresión general de miARN. El análisis de Volcano basado en los valores de P crudos, reveló la existencia de pocos miRNAs desregulados estando la mayoría de ellos sobre-expresados tras la ITV en comparación con la previa. Utilizando los 50 miRNAs que más se alteraban, no se observó una agrupación clara en función del tiempo, es decir, pre y post-ITV. Conclusiones: Nuestros resultados indican que la ITV tiene poco efecto en el patrón de expresión de miARN en sangre completa

Genome-wide copy number profiling of mouse neural stem cells during differentiation.

There is growing evidence that gene amplifications were present in neural stem and progenitor cells during differentiation. We used array-CGH to discover copy number changes including gene amplifications and deletions during differentiation of mouse neural stem cells using TGF-ß and FCS for differentiation induction. Array data were deposited in GEO (Gene Expression Omnibus, NCBI) under accession number GSE35523. Here, we describe in detail the cell culture features and our TaqMan qPCR-experiments to validate the array-CGH analysis. Interpretation of array-CGH experiments regarding gene amplifications in mouse and further detailed analysis of amplified chromosome regions associated with these experiments were published by Fischer and colleagues in Oncotarget (Fischer et al., 2015). We provide additional information on deleted chromosome regions during differentiation and give an impressive overview on copy number changes during differentiation induction at a time line.

Exome sequencing for mucolipidosis III: Detection of a novel GNPTAB gene mutation in a patient with a very mild phenotype.

Mucolipidosis II and III alpha/beta (ML II/III alpha/beta) are rare autosomal recessive lysosomal storage diseases that are caused by a deficiency of UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase, the enzyme responsible for the synthesis of the mannose 6-phosphate targeting signal on lysosomal hydrolases. A Brazilian patient suspected of having a very mild ML III was investigated using whole next-generation sequencing (NGS). Two mutations in the GNPTAB gene were detected and confirmed to be in trans status by parental analysis: c.1208T>C (p.Ile403Thr), previously reported as being pathogenic, and the novel mutation c.1723G>A (p.Gly575Arg). This study demonstrates the effectiveness of using whole NGS for the molecular diagnosis of very mild ML III alpha/beta patients.

Successful treatment of advanced ovarian cancer with thermochemotherapy and adjuvant immune therapy.

We report on a 4-year progression-free survival of a 54-year-old female first diagnosed in December 2007 with advanced bilateral ovarian cancer FIGO IIIc, disseminated peritoneal carcinosis and malignant diaphragm invasion. Treatment started in January 2008 with 6 cycles of Taxol 175 mg/m(2)/carboplatin AUC 5 in 3-week intervals. Twenty-four hours following each chemotherapy session, fever-range long-duration whole-body hyperthermia (WBH) was performed at the temperature plateau of 40°C body core temperature for 6 h. Three months after completion of chemotherapy, 4 more long-duration WBH procedures were performed in monthly intervals. Importantly, long-duration WBH was paralleled with intradermal vaccination of autologous dendritic cells. No other treatment was given to the patient. Four years following the first diagnosis, the patient is still in complete remission with no evidence of disease.

An integrated approach to assess air pollution threats to cultural heritage in a semi-confined environment: the case study of Michelozzo's Courtyard in Florence (Italy).

An example of an integrated approach to assess air pollution threats to cultural heritage in a semi-confined environment is presented in this work, where the monitoring campaign carried out at the Michelozzo's Courtyard (in Palazzo Vecchio, Florence, Italy) is used as a case study. A wide research project was carried out, with the main aim of obtaining the first quantitative data on air quality and microclimate conditions inside the Courtyard, and, if possible, identifying the main causes of degradation and suggesting appropriate conservation strategies. The investigation adopted a holistic approach involving thermographic measurements on the wall paintings, microclimatic analysis, gaseous pollutant monitoring, atmospheric particles characterisation and dry deposition compositional analysis. Attention was focused on the wall painting depicting the city of Hall because of its anomalous and critical conservation conditions, which are visible at a glance, due to the contrast between a wide darker zone around the central subject of the painting and external lighter areas.

Combining gene expression signatures and autoantibody profiles in human meningioma.

Gene expression profiling has emerged as powerful technique for studying the mechanisms of tumor genesis and development. Seroreactivity profiling of tumor antigens is a more recent technique that further contributes to the understanding of tumors and that offers itself for noninvasive tumor diagnosis. We performed expression profiling of 55,000 transcripts and expressed-sequence-tags for 24 meningiomas and related these data to autoantibody profiles of more than 50 antigens immunogenic in the autologous patients. The expression values of antigens in WHO grade I meningioma were significantly higher if the patients' sera reacted with these antigens as confirmed by a two-tailed Wilcoxon-Mann-Whitney test. Specifically, KIAA1344 that was previously identified as frequent antigen marker in meningioma, showed increased expression if antigens against KIAA1344 were detected in autologous patients. Our study is the first to combine genome-wide expression signatures and comprehensive seroreactivity patterns toward a more complete view on tumor immunology, especially concerning the overall role of the level of gene expression on the immunogenicity of meningioma antigens.

Intraosseous intracranial meningioma.

Primary intraosseous lytic meningiomas are rare tumors, with only 16 cases described in the literature. We present a case in which CT and MR imaging with contrast agent helped diagnose preoperatively an enlarging skull mass as a primary intraosseous lytic meningioma in a 70-year-old woman. Radiographic findings revealed a lytic mass centered on the coronal suture line that separated and thinned both the outer and inner tables of the frontal bone.

Physical, mental, and social predictors of functional outcome in unilateral lower-limb amputees.

OBJECTIVE: To study the value of physical, mental, and social characteristics as predictors of functional outcome of elderly amputees. DESIGN: Prospective, inception cohort study; comparisons with reference populations. SETTING: Main hospitals, rehabilitation centers, nursing homes, patients' own residence settings in 1 of the 3 northern provinces in the Netherlands. PARTICIPANTS: Forty-six patients older than 60 years, with unilateral transtibial or transfemoral amputation or knee disarticulation because of vascular disease. INTERVENTIONS: Measurement of physical, mental, and social predictors 2 and 6 weeks postamputation. MAIN OUTCOME MEASURES: The Sickness Impact Profile (SIP-68), Groningen Activity Restriction Scale (GARS), Timed up and go (TUG) test, and prosthetic use. RESULTS: A total of 15% of amputees died within the first year after amputation. Seventy percent lived independently at home 1 year postamputation. The functional level of the patients was low, as shown by high scores on the SIP-68 (mean, 23.6), GARS (mean, 41.2), and TUG test (mean, 23.9s). Functionally effective prosthetic use, as measured with the classification of Narang and Pohjolainen, was reached by 49%. For the SIP-68 scores, age, comorbidity, 1-leg balance, and the 15-word test predicted functional outcome in 69% of amputees. For the GARS score, age, 1-leg balance, and the 15-word test predicted functional outcome in 64%. For the TUG test, age and 1-leg balance predicted functional outcome in 42% of amputees. After correction for age, the only significant predictor for prosthetic use was 1-leg balance. CONCLUSIONS: Elderly patients with a leg amputation had a low functional level 1-year postamputation. An important part of functional outcome could be predicted 2 weeks after amputation by age at amputation, 1-leg balance on the unaffected limb, and cognitive impairment. Severe comorbidity probably also played a role. The results may be used in the general policy concerning leg amputees.

Concurrent validity of questionnaire and performance-based disability measurements in patients with chronic nonspecific low back pain.

This study aimed to investigate the concurrent validity of two approaches to disability measurement in patients with chronic nonspecific low back pain (CLBP). It was hypothesized that if both are measuring the same construct, the instruments would lead to similar disability results and would correlate strongly (r > 0.75). The study compared the results of self-reported and performance-based measures of disability in 64 consecutive patients with CLBP. Participants mean age was 38.0 years, the mean duration of the current episode of back pain 9.9 months, and 90% were off work due to CLBP. The self-report measures used were: the Roland Disability Questionnaire (Roland); the Oswestry Disability Questionnaire (Oswestry); and the Quebec Back Pain Disability Questionnaire (Quebec). Performance was measured using the Isernhagen Work Systems Functional Capacity Evaluation (FCE). The mean scores from the self-report measure are as follows: Roland 13.5 (scale 0-24), Oswestry 28.2 (scale 0-100), Quebec 37.8 (scale 0-100) consistent with moderate to severe disability. In contrast the results from the performance-based measures suggested that the subjects should be able to work at a physical intensity level of moderate to heavy. Little to moderate correlation was observed between the self-report and performance-based measures (Spearman rank correlations: Roland-FCE (-0.20), p > 0.05; Oswestry-FCE (-0.52), p < 0.01; Quebec-FCE (-0.50), p < 0.01). Results are interpreted to suggest that both performance-based and self-report measures of disability should be used in order to obtain a comprehensive picture of the disability in patients with CLBP.

Job satisfaction and health experience of people with a lower-limb amputation in comparison with healthy colleagues.

OBJECTIVES: To describe indicators of job dissatisfaction among amputee employees and to compare job satisfaction and health experience of working amputee employees with that of control subjects. DESIGN: A cross-sectional study, mailed questionnaire. SETTING: Patients were recruited by the orthopedic workshops of the Netherlands. PARTICIPANTS: One hundred forty-four patients who had an acquired unilateral major amputation of the lower limb at least 2 years before, were aged 18 to 60 years (mean age, 43y), and were living and working in the Netherlands. One hundred forty-four control subjects matched for age, gender, and type of job. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Statistical analysis of responses to a questionnaire regarding patient characteristics and amputation-related factors, amputee patients' opinions about their work and the social atmosphere at work, and their general health (RAND 36-Item Health Survey [RAND-36]). RESULTS: People with an amputation had greater job satisfaction (70%) than did the able-bodied control group (54%). The wish for (better) modifications in the workplace and the presence of comorbidity were significantly related to job dissatisfaction in people with limb loss. Amputee employees were less often hindered by the failures of others and by fluctuations in temperature. People with limb loss showed a worse physical health experience than controls on the RAND-36. CONCLUSIONS: The vocational satisfaction of people with limb loss may be improved by better workplace modifications, depending on the functional capabilities of the person and the functional demands of the job; improvement may also be achieved by vocational rehabilitation programs, especially for those with an amputation in combination with other morbidity. Despite experiencing more health problems, the amputee group expressed greater job satisfaction than the able-bodied group, reflecting a great appreciation of job reintegration by people with a lower-limb amputation.

Analysis of thermal properties of wheelchair cushions with thermography.

Thermal properties of wheelchair cushions have been traditionally studied with thermistor probes, which provide temperature values of limited areas (spot analysis). In this paper, we describe a novel procedure based on thermography for assessing the distribution of temperature over the entire surface of wheelchair cushions. The thermal transient during contact with the body (heating phase) and after use (cooling phase) is considered. The procedure was tested in four different seat cushions (with a gel pad, air-filled cells, gel-filled bubbles and foam-filled bubbles) used by a normal subject. Observed results were compatible with the predicted outcomes based on an analysis of the materials and structures. Specifically: (i) air-filled cushions exhibited the fastest thermal transients, gel cushions the slowest transients, while cushions with a mixed structure exhibited intermediate behaviour; (ii) cushions made from flat surfaces of foam exhibited the highest peak temperatures (30.8 degrees C) as compared to those with air-filled cells (30.35 degrees C) or bubble-shaped surfaces (29.7 degrees C); (iii) the average temperature under the thighs was significantly higher than that under the ischiatic area in all cushions (29.6 degrees C compared with 28.7 degrees C, p < 0.05). It is shown that the present method can be used to differentiate between different cushions. Although the 'macro-analysis' inherent in thermography appears to be suited for improving cushion design, this approach should be further investigated to determine its reliability.

Geographic heterogeneity of 4 common worldwide cystic fibrosis non-DF508 mutations in Brazil.

Cystic fibrosis (CF) is an autosomal recessive disease caused by at least 750 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The frequency of the most common mutation (DF508) in Brazilian patients of European origin is 47%. To determine the frequency of 4 other common CF mutations (G542X, G551D, R553X, and N1303K) in Brazilian patients of European origin, we used direct polymerase chain reaction (PCR) amplification of DNA obtained from dried blood spots on Guthrie cards. The DNA came from 247 non-DF508 chromosomes from 172 Brazilian CF patients ascertained from 5 different states of Brazil. The results show that the 4 mutations account for 17% of the non-DF508 alleles and only 9% of the total number of Brazilian CF alleles. Overall, the frequency of each mutation is different from northern European and North American populations but similar to southern European populations, mainly the Italian and Spanish populations. When Brazilian patients of European origin are grouped according to state of birth, the frequencies of the mutations are significantly different between southern and southeastern states of Brazil. Therefore there are serious implication for risk assessment of DNA-based tests in heterogeneous populations such as Brazilians. Further studies are needed to identify the remaining 44% of CF mutations for the different populations and regions of Brazil.

Cystic fibrosis in the Brazilian population: DF508 mutation and KM-19/XV-2C haplotype distribution.

We have used PCR amplification of DNA obtained from Guthrie cards to identify the DF508 mutation and correlate it with the allele frequencies at two polymorphic loci (XV-2C and KM-19) closely linked to the cystic fibrosis gene. The DNA came from 193 white Brazilian families affected by cystic fibrosis and living in five different states of Brazil. The distribution of the haplotypes derived from the DF508 and non-DF508 XV-2C/KM-19 genotypes indicates that 88% of the DF508 alleles are linked to haplotype B and suggests that high heterogeneity exists among the non-DF508 cystic fibrosis alleles occurring in different states. Our data can be used to compare linkage disequilibrium between Brazilians and other heterogeneous populations where the DF508 mutation frequency is low and where many different rare mutations account for the remaining recessive cystic fibrosis alleles.

Regional distribution of cystic fibrosis-linked DNA haplotypes in Brazil: multicenter study.

The restriction fragment length polymorphism (RFLP) haplotypes of cystic fibrosis (CF) alleles vary between populations. To determine the distribution of two RFLPs (XV-2C and KM-19) that are tightly linked to the CF locus, we analyzed a white sample from five different states of Brazil. The haplotypes of 314 CF- and 237 non-CF-bearing chromosomes were uniformly distributed over the five states. The XV-2C allele and haplotype frequencies and the degree of linkage disequilibrium were determined. These were similar to values previously reported in southern European countries but different from results reported for northern and central Europe and North America. In contrast, although KM-19 allele frequencies differed between Brazilian states and European and North American countries, these frequencies were similar to values reported in black Americans. A significant proportion of Brazilian CF-bearing chromosomes had less common haplotypes, suggesting a heterogeneous distribution of CF gene mutations among Brazilians. Further studies are needed to identify the mutations affecting the Brazilian CF patients with various haplotypes.