The macro-metastasis/organ parenchyma interface (MMPI) - A hitherto unnoticed area.

The macro-metastasis/organ parenchyma interface (MMPI) was previously considered an inert anatomical border which sharply separates the affected organ parenchyma from the macro-metastatic tissue. Recently, infiltrative growth of macro-metastases from various primary tumors was described in the brain, liver and lung, with significant impact on survival. Strikingly, the MMPI patterns differed between entities, so that at least nine different patterns were described. The MMPI patterns could be further classified into three major groups: displacing, epithelial and diffuse infiltrating. Additionally, macro-metastases are a source of further tumor cell dissemination in the affected organ; and these intra-organ metastatic dissemination tracks starting from the MMPI also vary depending on the anatomical structures of the colonized organ and influence disease outcome. In spite of their relevance, MMPIs and organ-specific dissemination tracks are still largely overlooked by many clinicians, pathologists and/or researchers. In this review, we aim to address this important issue and enhance our current understanding of the different MMPI patterns and dissemination tracks in the brain, liver and lung.

Meshes in a mess: Mesenchymal stem cell-based therapies for soft tissue reinforcement.

Surgical meshes are frequently used for the treatment of abdominal hernias, pelvic organ prolapse, and stress urinary incontinence. Though these meshes are designed for tissue reinforcement, many complications have been reported. Both differentiated cell- and mesenchymal stem cell-based therapies have become attractive tools to improve their biocompatibility and tissue integration, minimizing adverse inflammatory reactions. However, current studies are highly heterogeneous, making it difficult to establish comparisons between cell types or cell coating methodologies. Moreover, only a few studies have been performed in clinically relevant animal models, leading to contradictory results. Finally, a thorough understanding of the biological mechanisms of mesenchymal stem cells in the context of foreign body reaction is lacking. This review aims to summarize in vitro and in vivo studies involving the use of differentiated and mesenchymal stem cells in combination with surgical meshes. According to preclinical and clinical studies and considering the therapeutic potential of mesenchymal stem cells, it is expected that these cells will become valuable tools in the treatment of pathologies requiring tissue reinforcement. STATEMENT OF SIGNIFICANCE: The implantation of surgical meshes is the standard procedure to reinforce tissue defects such as hernias. However, an adverse inflammatory response secondary to this implantation is frequently observed, leading to a strong discomfort and chronic pain in the patients. In many cases, an additional surgical intervention is needed to remove the mesh. Both differentiated cell- and stem cell-based therapies have become attractive tools to improve biocompatibility and tissue integration, minimizing adverse inflammatory reactions. However, current studies are incredibly heterogeneous and it is difficult to establish a comparison between cell types or cell coating methodologies. This review aims to summarize in vitro and in vivo studies where differentiated and stem cells have been combined with surgical meshes.

RNA-Seq reveals large quantitative differences between the transcriptomes of outbreak and non-outbreak locusts.

Outbreaks of locust populations repeatedly devastate economies and ecosystems in large parts of the world. The consequent behavioural shift from solitarious to gregarious and the concomitant changes in the locusts' biology are of relevant scientific interest. Yet, research on the main locust species has not benefitted from recent advances in genomics. In this first RNA-Seq study on Schistocerca gregaria, we report two transcriptomes, including many novel genes, as well as differential gene expression results. In line with the large biological differences between solitarious and gregarious locusts, almost half of the transcripts are differentially expressed between their central nervous systems. Most of these transcripts are over-expressed in the gregarious locusts, suggesting positive correlations between the levels of activity at the population, individual, tissue and gene expression levels. We group these differentially expressed transcripts by gene function and highlight those that are most likely to be associated with locusts' phase change either in a species-specific or general manner. Finally, we discuss our findings in the context of population-level and physiological events leading to gregariousness.

Evolution, expression and association of the chemosensory protein genes with the outbreak phase of the two main pest locusts.

We analyze the evolutionary relationships and expression patterns of the large set of genes for chemosensory proteins (CSPs) in the two main pest locusts. We used the available transcriptome and genome data to infer the number of genes using BLAST searches and sequence similarity matrices. Maximum likelihood phylogenies revealed the relationships between these CSPs and CSPs from several arthropods. RNAseq and qPCR allowed associating CSPs to locust phases. Crossing the phylogenetic and expression data allowed us to deduce homologies and conservation of the involvement in the phase change. We confirm that Locusta migratoria has at least 58 CSP gene copies, only five of which lack evidence of expression, and we reveal that Schistocerca gregaria has at least 42 expressed CSP genes. Both species share 21 orthologs, whereas 33 L. migratoria and 15 S. gregaria CSPs seem species-specific. Additional six S. gregaria and four L. migratoria CSPs seem duplications. Although the expression profiles are not especially conserved, seven orthologous CSP pairs share a gregarious over-expression pattern in adult locusts. We thus confirm that the number of locusts' CSPs is large, due to gene duplications during the evolution of Orthoptera, we establish sequence and potential functional homologies, and we highlight specific CSPs that appear to be involved in locust gregariousness either in general or in a species-specific manner.

[Extra-abdominal umbilical vein varix. A case report]. / Variz venosa umbilical intramniótica. Reporte de un caso.

UNLABELLED: The intra-abdominal umbilical vein varix is very uncommon, characterized by a dilation of the vein, usually located between its entry into the abdomen and completion in the portal system. However, the location of this anomaly to extra-abdominal level is very unusual and more difficult to diagnose by ultrasound. CLINICAL CASE: We present a case undiagnosed during pregnancy, demonstrating cord abnormality in its extra-abdominal portion and confirmed later by the pathology study. It was a gestation of 36 + 6 weeks, ending by performing emergency caesarean section for abnormal fetal heart rate, with good perinatal outcome. The diagnosis was made after placental delivery, by the existence of fibrotic cystic structure in the middle third of the umbilical cord.

A step to the gigantic genome of the desert locust: chromosome sizes and repeated DNAs.

The desert locust (Schistocerca gregaria) has been used as material for numerous cytogenetic studies. Its genome size is estimated to be 8.55 Gb of DNA comprised in 11 autosomes and the X chromosome. Its X0/XX sex chromosome determinism therefore results in females having 24 chromosomes whereas males have 23. Surprisingly, little is known about the DNA content of this locust's huge chromosomes. Here, we use the Feulgen Image Analysis Densitometry and C-banding techniques to respectively estimate the DNA quantity and heterochromatin content of each chromosome. We also identify three satellite DNAs using both restriction endonucleases and next-generation sequencing. We then use fluorescent in situ hybridization to determine the chromosomal location of these satellite DNAs as well as that of six tandem repeat DNA gene families. The combination of the results obtained in this work allows distinguishing between the different chromosomes not only by size, but also by the kind of repetitive DNAs that they contain. The recent publication of the draft genome of the migratory locust (Locusta migratoria), the largest animal genome hitherto sequenced, invites for sequencing even larger genomes. S. gregaria is a pest that causes high economic losses. It is thus among the primary candidates for genome sequencing. But this species genome is about 50 % larger than that of L. migratoria, and although next-generation sequencing currently allows sequencing large genomes, sequencing it would mean a greater challenge. The chromosome sizes and markers provided here should not only help planning the sequencing project and guide the assembly but would also facilitate assigning assembled linkage groups to actual chromosomes.

Similar antiviral efficacy and tolerability between efavirenz and lopinavir/ritonavir, administered with abacavir/lamivudine (Kivexa), in antiretroviral-naïve patients: a 48-week, multicentre, randomized study (Lake Study).

BACKGROUND: Although efavirenz and lopinavir/ritonavir(r) are both recommended antiretroviral agents in antiretroviral-naïve HIV-infected patients, there are few randomized comparisons of their efficacy and tolerability. METHODS: A multicenter and randomized study was performed including 126 antiretroviral-naïve patients, randomly assigned to efavirenz+Kivexa (n=63) or lopinavir/r+Kivexa (n=63). Efficacy endpoints were the percentage of patients with HIV-RNA < or =50 copies/mL at week 48 and CD4 recovery. Safety was assessed by comparing toxicity and discontinuations. Statistical analyses were performed on an intention-to-treat (ITT) basis (Missing=Failure). RESULTS: At week 48, 56.7% of patients in the efavirenz and 63.2% in the lopinavir/r groups showed HIV-1 RNA <50 copies/mL (P=0.770) (intention-to-treat analysis; Missing=Failure). Only 1 (1.53%) patient from each group experienced virological failure. CD4 values increased in both groups (298 cells in the efavirenz group, P=0.001; 249 cells in the lopinavir/r group, P=0.002; P=0.126 between groups). HDL-cholesterol only increased in the efavirenz group (from 39+/-12 mg/dL to 49+/-11; P=0.001). Discontinuations were more frequent in the lopinavir/r group (36.5% versus 28.5%; P=0.193), but more patients with efavirenz interrupted due to toxicity (11.1% versus 6.3%); most of them were attributed to hypersensitivity reaction. CONCLUSIONS: Similar virological efficacy was observed for efavirenz and lopinavir/r, when administered with Kivexa in antiretroviral-naïve patients, while immunological improvement was slightly superior for efavirenz. The higher rate of discontinuation due to toxicity in the efavirenz group was related to a higher incidence of hypersensitivity reaction. Nowadays, the use of the new formulation of lopinavir/r and the HLA-B*5701 genotype test before starting abacavir should improve the safety profiles of these regimens.

Methanogenic toxicity in anaerobic digesters treating municipal wastewater.

In upflow anaerobic sludge blanket (UASB) digesters treating raw sewage at low temperatures, the sludge progressively lost methanogenic activity, indicating the possibility of methanogenic activity inhibition caused by wastewater constituents. To check this fact, batch and semi-continuous methanogenic toxicity assays were carried out with raw and centrifuged sewage. Permanent methanogenic toxicity on anaerobic sludge of approximately 50% was found when the sludge exposure to wastewater was renewed in a semi-continuous way. A stronger methanogenic inhibition of about 70-100% was observed when an active anaerobic sludge was exposed to mixed liquor from the UASB digester treating municipal wastewater. Suspended solids removal from sewage slightly reduced methanogenic toxicity. Effective concentration of municipal wastewater that caused a 50% reduction in methanogenic activity was estimated to be in the range of 150-200 mg CODl(-1). As methanogenic inhibition appeared to be related to remaining COD, higher methanogenic toxicity in digesters operating with low conversion efficiency will be expected.

Sustained antiretroviral treatment adherence in survivors of the pre-HAART era: attitudes and beliefs.

The objective of this study was to assess adherence of HIV-1-infected patients who started treatment in the pre-HAART era and to determine variables associated with better adherence, including relevant attitudes and beliefs. This is a cross-sectional study enrolling patients who had received antiretroviral therapy for >or=10 years. Adherence was evaluated through self-reporting and plasma drug concentrations. Treatment variables, attitudes and beliefs were collected during structured interviews. The results show that for 87 patients the median (interquartile range) time on therapy was 13 (10-19) years; 80 were on therapy at the time of analysis. Adherence was >or=95% in 54 patients (67.5%), 90-94% in 22 (27.5%) and <90% in 4 (5%). Drug concentrations were below the lower limit of detection in five patients. Younger age (p=0.014), female gender (p=0.005), current substance abuse (p=0.004) and hepatitis C virus co-infection (p<0.001) were related to lower adherence. Adherence did not differ in relation to different drug families or once- or twice-daily regimens. Patients with adherence <95% were more likely to have interrupted treatment without doctor's recommendation (p=0.009). Adherent patients exhibited a higher perception of risk of developing the illness and of benefits of therapy, higher self-efficacy and intention to adhere and were more influenced by events that motivate medication intake. To conclude, adherence was >90% in most patients on antiretroviral therapy for >or=10 years. Adherence was more related to beliefs about health and illness than to the characteristics of medication or level of knowledge about treatment. Care adherence interventions should include assessment of health beliefs.

Characteristics and anaerobic treatability of municipal and industrial estate wastewaters.

Centralised treatment of domestic sewage coming from A Coruña city (250000 inhabitants) and several medium and small size villages (up to 15000 inhabitants) together with industrial estate effluents was planned. The area population is about 380000 inhabitants and the overall effluent will reach about 600000 equivalent inhabitants. The characteristics of different streams will determine the treatment alternatives and pre-treatment requirements for individual streams. Domestic sewage from A Coruña showed medium to high organic content (741 mg l(-1) of COD), while domestic sewage from small villages (Lorbé, Oleiros) and industrial estates (Sabón, A Grela) showed a high variability in organic content, with COD concentration ranging from 100 to 4000 mg L(-1) or more. About 50-65% COD corresponded to suspended solids, although some industrial effluents showed lower values. Characterized industrial effluents had lower concentration of nutrients (nitrogen and phosphorus) and higher concentration of sulphate and alkalinity than domestic sewage. Anaerobic biodegradability was about 80% for domestic sewage, and ranged from 20 to 100% for industrial estate effluents. Furthermore, some industrial streams showed high microbial toxicity. The results indicate that anaerobic treatment of these effluents is of interest. However, specific pre-treatment for some individual streams or the adoption of minimisation and prevention measures in order to reach total or partial detoxification is suggested.

Nosocomial bloodstream infections caused by Streptococcus pneumoniae.

A retrospective study of Streptococcus pneumoniae bacteraemia among adult patients in two large teaching hospitals in Spain identified 108 (10.6%) of 1,020 episodes as nosocomial pneumococcal bloodstream infections (NPBIs). Seventy-seven clinical records with sufficient data were available for analysis. The interval between admission and a positive blood culture was 3--135 days (median 17 days; interquartile range 8--27). The main underlying and predisposing conditions for NPBI were malignancy (31%), chronic obstructive pulmonary disease (28.6%), heart failure (16.9%), chronic renal failure (15.6%), liver cirrhosis (13%) and infection with human immunodeficiency virus (13%). Overall, 31.2% of patients developed severe sepsis, 11.7% septic shock, and 3.9% multi-organ failure. The main portals of entry were pneumonia (70.1%), meningitis (5.2%) and primary peritonitis (5.2%). Of the responsible serogroups, 78% were included in the 23-valent polysaccharide vaccine. Thirty-five (45.5%) patients died, with death considered to be related to the NPBI in 21 (27.3%) cases. Following multivariate analysis, factors that independently predicted death after adjusting for age were: ultimately fatal underlying disease (OR, 8.9; 95% CI, 0.8--94.3; p<0.001); rapidly fatal underlying disease (OR, 15.0; 95% CI, 2.8--81.3; p<0.001); heart failure (OR, 8.11; 95% CI, 1.1--60.8; p<0.03); inadequate empirical therapy (OR, 10.6; 95% CI, 1.2--97; p<0.003); a severe sepsis score (OR, 9.5; 95% CI, 1.9--47.0; p<0.001); and septic shock or multi-organ failure (OR, 63.7; 95% CI, 4.9--820.7; p<0.001). Adequate empirical therapy was an independent protective factor (OR, 0.05; 95% CI, 0.04--0.58; p<0.005), but the use of more than one antimicrobial agent was not.

Sensitivity of urinary antigen test in relation to clinical severity in a large outbreak of Legionella pneumonia in Spain.

Presented here are the results of Legionella urinary antigen testing correlated with patient characteristics and severity of pneumonia (Fine score) in 295 patients diagnosed with Legionella pneumonia in connection with a large outbreak in Murcia, Spain. Overall, the sensitivity of the urinary antigen test was 47.7% (141/295). A statistically significant association was found between the clinical severity of pneumonia and test sensitivity; 85.7% for patients with severe pneumonia versus 37.9% for patients with mild pneumonia (risk ratio, 2.3). Variables significantly associated with test positivity in multivariate analysis were as follows: pre-existing pulmonary disease, body temperature >40 degrees C, leukocytosis and multilobar infiltrates. Patients with mild pneumonia may go undiagnosed if the urinary antigen test is used alone.

Therapeutic immunization with an inactivated HIV-1 Immunogen plus antiretrovirals versus antiretroviral therapy alone in asymptomatic HIV-infected subjects.

To determine whether the addition of an inactivated-gp120-depleted HIV-1 Immunogen to antiretrovirals (ARTs) conferred a beneficial effect on delaying time to virologic failure relative to that obtained by ARTs alone, a phase II clinical trial was performed in 243 asymptomatic, ART naïve, HIV-1 seropositive adults. The Cox model showed that HIV-1 Immunogen treatment was associated with a 34% decrease in the risk of virologic failure (P = 0.056). When the analysis incorporated baseline HIV-RNA stratification the risk of virologic failure in the HIV-1 Immunogen Arm was significantly reduced a 37% compared to the IFA placebo Arm (P = 0.034). The data suggest that therapeutic immunization plus ARTs could influence virologic control.

Use of direct latex agglutination testing of selective broth in the detection of group B strepptococcal carriage in pregnant women.

Direct latex agglutination testing of selective broth medium for the detection of group B streptococci was evaluated. Results were compared with those obtained by the recommended subculture method. Among the 551 vaginal-rectal specimens tested, 101 (18.3%) were positive by the subculture method. Of these subcultures, latex agglutination testing detected 99 (98%) positive specimens. Agglutination testing of selective broth is a sensitive method which offers the advantage of saving 24 h in the turnaround time for detection of group B streptococci in pregnant women.

[Antimicrobial susceptibility of Pseudomonas aeruginosa clinical isolates in Murcia, Spain]. / Sensibilidad a antimicrobianos de aislamientos clínicos de Pseudomonas aeruginosa en Murcia.

The source and antimicrobial susceptibility of 1293 clinical isolates of Pseudomonas aeruginosa obtained from 1996 to 1999 were studied. Urine was the most common source for outpatient isolates (61.2%), while for hospitalized patients respiratory samples were the most frequent (40.2%). The most active antimicrobials with resistance rates <=10% were ceftazidime, imipenem, tobramycin and amikacin. By contrast, aztreonam, ciprofloxacin and gentamicin showed resistance levels >10%. The percentages of resistance to ceftazidime, aztreonam and imipenem in isolates from inpatients and from patients in the intensive care unit were significantly higher than those in isolates from outpatients and other clinical departments. Comparison of susceptibility data from 1996 to 1999 showed a significant increase in the resistance rate for all of the antibiotics studied but imipenem.

The effect of BCG vaccination on tuberculin reactivity and the booster effect among hospital employees.

BACKGROUND: We estimated the effect of remote BCG vaccination on tuberculin reactivity and the booster effect among hospital employees. METHODS: Cross-sectional survey at a university hospital. All personnel employed during a 24-month period were included in the study. Employees were administered 2-step tuberculin testing, and BCG vaccination scars were verified. RESULTS: Of 665 hospital employees studied, 239 (36%) had been vaccinated with BCG in childhood. Significant tuberculin reactions (> or =5 mm) were more frequent among BCG-vaccinated (60%) than among nonvaccinated (29%) employees (odds ratio [OR], 3.6; 95% confidence interval [CI], 2.6-5.2). The predictive value of tuberculosis infection increased with increasing reaction size and greater age (from 37% in subjects 30 years or younger with indurations > or =5 mm to 100% in subjects 50 years or older with indurations > or =15 mm). Among 374 employees with a negative tuberculin test reaction who underwent a second test, 39 (43%) of 91 vaccinated subjects had a positive booster reaction in contrast to 51 (22%) of 232 nonvaccinated subjects (OR, 3.4; 95% CI, 2-5.7). Neither different size criteria nor different definitions of the booster effect had an impact on the predictive value of tuberculosis infection. CONCLUSIONS: Remote BCG vaccination largely influences the tuberculin reaction and the boosting phenomenon among hospital employees. The interpretation of the results of 2-step tuberculin testing in a BCG-vaccinated subject must take into account age, size of the reaction, and local prevalence of tuberculosis infection. No single criterion, however, can accurately separate reactions caused by true infection from those caused by BCG vaccination.