A comparison of the tube forming potentials of early and late endothelial progenitor cells

The identification of circulating endothelial progenitor cells (EPCs) has revolutionized approaches to cell-based therapy for injured and ischemic tissues. However, the mechanisms by which EPCs promote the formation of new vessels remain unclear. In this study, we obtained early EPCs from human peripheral blood and late EPCs from umbilical cord blood. Human umbilical vascular endothelial cells (HUVECs) were also used. Cells were evaluated for their tube-forming potential using our novel in vitro assay system. Cells were seeded linearly along a 60 μm wide path generated by photolithographic methods. After cells had established a linear pattern on the substrate, they were transferred onto Matrigel. Late EPCs formed tubular structures similar to those of HUVECs, whereas early EPCs randomly migrated and failed to form tubular structures. Moreover, late EPCs participate in tubule formation with HUVECs. Interestingly, late EPCs in Matrigel migrated toward pre-existing tubular structures constructed by HUVECs, after which they were incorporated into the tubules. In contrast, early EPCs promote sprouting of HUVECs from tubular structures. The phenomena were also observed in the in vivo model. These observations suggest that early EPCs cause the disorganization of pre-existing vessels, whereas late EPCs constitute and orchestrate vascular tube formation.     

Early versus late ST-segment resolution and clinical outcomes after percutaneous coronary intervention for acute myocardial infarction

Background. Absence of complete ST-segment resolution (STR) after percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction (STEMI) is a determinant of mortality. Traditionally, STR is determined on the coronary care unit (CCU) 60 to 90 minutes after the initiation of reperfusion therapy. We studied the prognostic value of STR immediately after PCI. Methods. We analysed 223 consecutive patients with STEMI and successful PCI. Continuous ECG data were collected during PCI and at 30 minutes after arrival on the CCU (mean time 81±17 minutes after reflow of the culprit artery). Patients were divided into three groups: patients with complete STR immediately after PCI (‘early’), patients with complete and persistent STR at 30 minutes on the CCU, but not immediately after PCI (‘late’) and patients without STR. One-year follow-up was obtained for death and rehospitalisation for major adverse cardiac events. Cox proportional hazards regression was used to evaluate the association between STR and outcome. Results. Early STR occurred in 115 (52%) and late STR in 43 (19%) patients. Patients with early or late STR had a lower incidence of one-year cardiac death than those without STR (1.9 vs. 9.2%; p=0.02). In contrast, rehospitalisation occurred more frequently in patients with early or late STR (20.3 vs. 6.2%; p=0.009). As compared with patients without STR, early and late STR had a similar prognostic value (hazard ratios [95% confidence interval] for cardiac death 0.40 [0.08-2.03] and 0.25 [0.03-2.08]). Conclusions. We found no (major) change in prognostic value of STR during the 0 to 90 minutes time window after PCI. (Neth Heart J 2010;18:416-22.)     

Factors Influencing Early and Late Mortality in Adults with Invasive Pneumococcal Disease in Calgary,Canada: A Prospective Surveillance Study

Background

Invasive pneumococcal disease continues to be an important cause of mortality. In Calgary, 60% of deaths occur within 5 days of presenting to hospital. This proportion has not changed since before the era of penicillin. The purpose of this study was to investigate what factors may influence death within 5 days of presentation with pneumococcal disease.

Methods and Findings

Demographic and clinical data from the CASPER (Calgary Area Streptococcus pneumoniae Epidemiology Research) study on 1065 episodes of invasive pneumococcal disease in adults (≥18 years) from 2000 to 2010 were analyzed. Adjusted multinomial regression was performed to analyze 3 outcomes: early mortality (<5 days post-presentation), late mortality (5-30 days post-presentation), and survival, generating relative risk ratios (RRR). Patients with severe disease had increased risk of early and late death. In multinomial regression with survivors as baseline, the risk of early death increased in those with a Charlson index ≥2 (RRR: 6.3, 95% CI: 1.8-21.9); the risk of late death increased in those with less severe disease and a Charlson ≥2 (RRR: 6.1, 95% CI: 1.4-27.7). Patients who never received appropriate antibiotics had 5.6X (95% CI: 2.4-13.1) the risk of early death. Risk of both early and late death increased by a RRR of 1.3 (95% CI: 1.2-1.4) per 5-year increase in age. In multinomial regression, there were no significant differences in the effects of the factors tested between early and late mortality.

Conclusions

Presenting with severe invasive pneumococcal disease, multiple comorbidities, and older age increases the risk of both early and late death. Patients who died early often presented too late for effective antibiotic therapy, highlighting the need for an effective vaccine.     

Stage-specific population dynamics of cottony cushion scale,Icerya purchasi (Hemiptera: Monophlebidae), in citrus orchards in Jeju,Korea

The cottony cushion scale, Icerya purchasi Maskell (Hemiptera: Monophlebidae), is a polyphagous, cosmopolitan and destructive pest of citrus. This study was conducted to obtain the stage-specific phenology of I. purchasi for seasonal management strategies in the field. Movement of crawlers (hatched nymphs) in egg sacs of overwintered females started in late May, peaked in early to mid-June, and was completed by late June. Generally, the 1st generation occurred from late May until late September and the overlapping second generation occurred from early September. The 1st nymphs in the 1st generation peaked in mid June. The 2nd nymphs showed peak activity in late July. The 3rd nymphs showed peak population in early September. The 1st generation adults peaked in mid September. In the 2nd generation, the 1st nymphs peaked in early October, the 2nd nymphs showed peak activity in late October, and the 3rd nymphs reached a plateau after mid October. The 2nd generation adults occurred from late October. Consequently, two life cycles were competed in the Jeju area. The average fertilities of I. purchasi were 623 and 247 crawlers per female in overwintered and summer generations, respectively. An average of 20.7% of all citrus orchards was infested with I. purchasi, with a mean of 3.9% infested trees in Jeju. These results should be useful in establishing management strategies for I. purchasi in citrus orchards.     

In vivo Macrophage Imaging Using MR Targeted Contrast Agent for Longitudinal Evaluation of Septic Arthritis

Macrophages are key-cells in the initiation, the development and the regulation of the inflammatory response to bacterial infection. Macrophages are intensively and increasingly recruited in septic joints from the early phases of infection and the infiltration is supposed to regress once efficient removal of the pathogens is obtained. The ability to identify in vivo macrophage activity in an infected joint can therefore provide two main applications: early detection of acute synovitis and monitoring of therapy.In vivo noninvasive detection of macrophages can be performed with magnetic resonance imaging using iron nanoparticles such as ultrasmall superparamagnetic iron oxide (USPIO). After intravascular or intraarticular administration, USPIO are specifically phagocytized by activated macrophages, and, due to their magnetic properties, induce signal changes in tissues presenting macrophage infiltration. A quantitative evaluation of the infiltrate is feasible, as the area with signal loss (number of dark pixels) observed on gradient echo MR images after particles injection is correlated with the amount of iron within the tissue and therefore reflects the number of USPIO-loaded cells.We present here a protocol to perform macrophage imaging using USPIO-enhanced MR imaging in an animal model of septic arthritis, allowing an initial and longitudinal in vivo noninvasive evaluation of macrophages infiltration and an assessment of therapy action.     

2-methylbutyryl-CoA dehydrogenase deficiency associated with autism and mental retardation: a case report

Pulmonary emphysema and bronchiectasis in HIV seropositive patients has been described in the presence of injection drug use, malnutrition, repeated opportunistic infections, such as Pneumocytis jirovici pneumonia and Mycobacterium tuberculosis infection, and has been linked to the presence of HIV virus in lung tissue. Given the high burden of pulmonary infections and malnutrition among people living with HIV in resource poor settings, these individuals may be at increased risk of developing pulmonary emphysema, potentially reducing the long term benefit of antiretroviral therapy (ART) if initiated late in the course of HIV infection. In this report, we describe three HIV-infected individuals (one woman and two children) presenting with extensive pulmonary cystic disease.     

Improved Outcome with Early Rifampicin Combination Treatment in Methicillin-Sensitive Staphylococcus aureus Bacteraemia with a Deep Infection Focus – A Retrospective Cohort Study

Introduction

Rifampicin has been used as adjunctive therapy in Staphylococcus aureus bacteraemia (SAB) with a deep infection focus. However, data for prognostic impact of rifampicin therapy is unestablished including the optimal initiation time point. We studied the impact of rifampicin therapy and the optimal initiation time for rifampicin treatment on prognosis in methicillin-sensitive S. aureus bacteraemia with a deep infection.

Methods

Retrospective, multicentre study in Finland including 357 SAB patients with a deep infection focus. Patients with alcoholism, liver disease or patients who died within 3 days were excluded. Patients were categorised according to duration of rifampicin therapy and according to whether rifampicin was initiated early (within 7 days) or late (7 days after) after the positive blood cultures. Primary end point was 90 days mortality.

Results

Twenty-seven percent of patients received no rifampicin therapy, 14% received rifampicin for 1-13 days whereas 59% received rifampicin ≥14 days. The 90 day mortality was; 26% for patients treated without rifampicin, 16% for rifampicin therapy of any length and 10% for early onset rifampicin therapy ≥14 days. Lack of rifampicin therapy increased (OR 1.89, p=0.026), rifampicin of any duration decreased (OR 0.53, p=0.026) and rifampicin therapy ≥14 days with early onset lowered the risk for a fatal outcome (OR 0.33, p<0.01) during 90 days follow-up.

Conclusion

Rifampicin adjunctive therapy for at least 14 days and initiated within 7 days of positive blood culture associated with improved outcome among SAB patients with a deep infection.     

Invasive <Emphasis Type="Italic">Aspergillus</Emphasis> Laryngotracheobronchitis in an Adult with Primary CNS Lymphoma

Invasive aspergillosis can be difficult to diagnose, and early recognition and initiation of therapy is imperative for improving patient outcomes. A case of invasive Aspergillus laryngotracheobronchitis is presented here with a review of the relevant literature. A 58-year-old male undergoing treatment for CNS lymphoma presented with neutropenic sepsis and acute respiratory distress requiring intubation. Following extubation, he reported persistent hoarseness for 1-month duration and he was found to have pseudomembranous plaques and ulcers of the larynx, trachea, and right mainstem bronchus consistent with Aspergillus laryngotracheobronchitis. Invasive Aspergillus laryngotracheobronchitis should be considered in immunocompromised patients presenting with persistent hoarseness.     

A goose-sized anseriform bird from the late Oligocene of France: the youngest record and largest species of Romainvilliinae

We describe a new anseriform bird from the late Oligocene of Saint-André, Marseille, in southern France. Saintandrea chenoides, gen. et sp. nov. is the first avian species reported from the locality, which is well known for its mammalian fossils. The new species belongs to the extinct Romainvilliinae and represents the latest occurrence of the taxon, which was before only known from the late Eocene and early Oligocene of Europe. S. chenoides is also the largest species of Romainvilliinae and increases the known morphological diversity of the taxon. The identification of a goose-sized representative of the Romainvilliinae in the late Oligocene of Europe raises the possibility that some of the large late Paleogene or early Neogene Anseriformes with uncertain phylogenetic affinities also belong to this taxon.     

Integrated Middle Devonian chitinozoan and miospore zonation of the Amazonas Basin, northern Brazil

Middle Devonian chitinozoans were studied from 13 deep wells in the central part of the Amazonas Basin, northern Brazil, and compared with a newly established regional miospore zonation. Of the 23 chitinozoan species encountered, four are newly described: Ancyrochitina multibrachiata, Lagenochitina praeavelinoi, Ramochitina autasmirimense, and Ramochitina herculesi and seven species are retained in open nomenclature because of an insufficient number of well-preserved specimens. The stratigraphic intervals investigated herein correspond to three miospore interval range zones previously defined for the Amazonas Basin, namely, the Grandispora/Samarisporites spp. (GS); late Emsian-early Eifelian, Grandispora permulta (Per); late early Eifelian through the Eifelian-Givetian transition, and Geminospora lemurata-Chelinospora ex. gr. ligurata (LLi); early Givetian. A regional Middle Devonian chitinozoan biozonation, also consisting of three zones, is proposed for the investigated interval. These zones are the interval zone of Angochitina n. sp. A (early Eifelian), the interval zone of Alpenachitina eisenacki (late early to late Eifelian), and the total range zone of Ramochitina stiphrospinata (early Givetian).     

Incidence of radiation toxicity in cervical cancer and endometrial cancer patients treated with radiotherapy alone versus adjuvant radiotherapy

AimThe study was made to evaluate early and late toxicity in a diversified group of patients receiving definitive or adjuvant radiotherapy in terms of clinical diagnosis and treatment methods.BackgroundRadiotherapy is a standard way of treatment in cervical and endometrial cancer patients, both as definitive and adjuvant therapy. But every radiation treatment may be involved with toxicity.Materials and methodsA detailed analysis was performed of 263 patients with gynaecological cancer treated with definitive (90 patients with cervical cancer received radiochemotherapy or radiotherapy exclusively) and adjuvant radiotherapy (38 with cervical and 135 with endometrial cancer).ResultsAcute reactions were found in 51.3% and late reactions were found in 14.8% of patients. It was stated that early (p < 0.007) and late (p < 0.003) post radiation reaction appear more frequently in women treated with definitive than adjuvant radiotherapy. The analysis of the whole group revealed higher rate of toxicity, both early and late, in the gastrointestinal tract than in the urinary system (p < 0.004). Comparing the subgroups, it was found that intestinal reactions occurred more frequently in the definitive radiotherapy group than in the adjuvant one.The occurrence of side effects was associated with the prolongation of total irradiation time due to necessary interruptions of radiotherapy. The comparison of the subgroups showed that interruptions occurred more frequently in patients receiving definitive rather than adjuvant radiotherapy (17.7–2.9%).ConclusionsDefinitive radiotherapy compared with adjuvant treatment may by associated with higher percentage of side effects caused by dose of therapy and correlation with chemotherapy.     

Embryonic Development and Rates of Metabolic Activity in Early and Late Hatching Eggs of the Major Malaria Vector Anopheles gambiae

Anopheles gambiae eggs generally hatch at the completion of embryo development; two-three days post oviposition. However, staggered or delayed hatching has been observed whereby a single batch of eggs shows marked variation in time-to-hatch, with some eggs hatching 18 days post oviposition or later. The mechanism enabling delayed hatch has not been clearly elucidated but is likely mediated by environmental and genetic factors that either induce diapause or slow embryo development. This study aimed to compare metabolic activity and embryonic development between eggs collected from sub-colonies of the baseline Anopheles gambiae GAH colony previously selected for early or late time-to-hatch. Egg batches from early and late hatch sub-colonies as well as from the baseline colony were monitored for hatching. For both time-to-hatch selected sub-colonies and the baseline colony the majority of eggs hatched on day two post oviposition. Nevertheless, eggs produced by the late hatch sub-colony showed a significantly longer mean time to hatch than those produced by the early hatch sub-colony. The overall proportions that hatched were similar for all egg batches. CO₂ output between eggs from early and late hatch sub-colonies showed significant differences only at 3 and 7 days post oviposition where eggs from the early hatch and the late hatch sub-colony were more metabolically active, respectively. No qualitative differences were observed in embryo development between the sub-colonies. It is concluded that all viable embryos develop to maturity at the same rate and that a small proportion then enter a state of diapause enabling them to hatch later. As it has previously been shown that it is possible to at least partially select for late hatch, this characteristic is likely to involve genetic as well as environmental factors. Delayed hatching in An. gambiae is likely an adaptation to maximise reproductive output despite the increased risk of desiccation in an unstable aquatic environment.     

Development of Stepwise Osteogenesis-mimicking Matrices for the Regulation of Mesenchymal Stem Cell Functions

An extracellular microenvironment, including an extracellular matrix (ECM), is an important factor in regulating stem cell differentiation. During tissue development, the ECM is dynamically remodeled to regulate stem cell functions. Here, we developed matrices mimicking ECM remodeling during the osteogenesis of mesenchymal stem cells (MSCs). The matrices were prepared from cultured MSCs controlled at different stages of osteogenesis and referred to as “stepwise osteogenesis-mimicking matrices.” The matrices supported the adhesion and proliferation of MSCs and showed different effects on the osteogenesis of MSCs. On the matrices mimicking the early stage of osteogenesis (early stage matrices), the osteogenesis occurred more rapidly than did that on the matrices mimicking undifferentiated stem cells (stem cell matrices) and the late stage of osteogenesis (late stage matrices). RUNX2 was similarly expressed when MSCs were cultured on both the early stage and late stage matrices but decreased on the stem cell matrices. PPARG expression in the MSCs cultured on the late stage matrices was higher than for those cultured on the stem cell and early stage matrices. This increase of PPARG expression was caused by the suppression of the amount of β-catenin and downstream signal transduction. These results demonstrate that the osteogenesis-mimicking matrices had different effects on the osteogenesis of MSCs, and the early stage matrices provided a favorable microenvironment for the osteogenesis.     

Modelling HIV and MTB Co-Infection Including Combined Treatment Strategies

A new host-pathogen model is described that simulates HIV-MTB co-infection and treatment, with the objective of testing treatment strategies. The model includes CD4+ and CD8+ T cells, resting and activated macrophages, HIV and Mycobacterium tuberculosis (MTB). For TB presentation at various stages of HIV disease in a co-infected individual, combined treatment strategies were tested with different relative timings of treatment for each infection. The stages were early HIV disease, late HIV disease and AIDS. The main strategies were TB treatment followed by anti-retroviral therapy (ART) after delays of 15 days, 2 months and 6 months. ART followed by TB treatment was an additional strategy that was tested. Treatment was simulated with and without drug interaction. Simulation results were that TB treatment first followed by ART after a stage-dependent delay has the best outcome. During early HIV disease a 6 month delay is acceptable. During late HIV disease, a 2 month delay is best. During AIDS it is better to start ART after 15 days. However, drug interaction works against the benefits of early ART. These results agree with expert reviews and clinical trials.     

Enters the shrew,some considerations on the Miocene palaeobiogeography of Iberian insectivores

The fossil record of the Iberian insectivores forms a subset of those found in central Europe. Comparison of the late early to early late Miocene record of the two areas shows that, particularly during the late Early Miocene, central European taxa have transient occurrences in Spain. Most taxa appear earlier and survive longer in central Europe. A notable exception is the gymnure Galerix, which extirpates earlier in central Europe, except for a transient occurrence in Germany just prior to its extinction. The main period of insectivore migrations is the late middle Miocene, although some of the taxa that enter remain restricted to the coastal areas. Overall, the pattern of distribution in time and space is best explained by the preference of insectivores for humid environments, as were found during the early Miocene and re-appeared at the end of the middle Miocene.     

Ring chromosome 9 in a newborn male presenting with facial dysmorphia, hypospadias and skeletal abnormalities.

A newborn male presenting with a peculiar appearance, hypertonia, a flexum attitude, hypospadias and skeletal abnormalities was found to bear a r 9 chromosome. A phenotypic distinction between early and late presenting forms is discussed.     

New material of Chalicotheriidae (Perissodactyla,Mammalia) from the Late Miocene of Axios Valley,Macedonia (Greece) with the description of a new species

Chalicotheriids are rare in the late Miocene mammal localities of Axios Valley, Macedonia (Greece). The new campaign of excavations, since 1972, has provided some specimens, which are studied in this article. They are coming from two different localities. The late early Vallesian locality of Pentalophos 1 (PNT) has provided a skull and a mandible of an Ancylotherium. The morphological characters of the PNT material as the small size, the long snout, the shallow mandibular corpus, the strong cingulum in the teeth, the short tooth rows and the short M3/m3 indicate that it differs from the known Turolian species A. pentelicum and allow the erection of a new species, named Ancylotherium hellenicum n. sp., which can be used as a biostratigraphic marker of the Vallesian. The middle Turolian locality Prochoma 1 (PXM) has provided only one M3, which is determined to the chalicotheriine Anisodon macedonicus. This species was earlier described from the middle Turolian locality Vathylakkos 3 (VAT) and the late Turolian one of Dytiko 3 (DKO) of Axios Valley. The biogeography and biostratigraphy of the late Miocene chalicotheres of the Greco-Iranian Palaeoprovince (GRIP), as well as their palaeoecology are also discussed. The common chalicothere of GRIP is A. pentelicum, expanded from the Balkans to Afganistan and ranging stratigraphically from the early to the late Turolian. Chalicotherium goldfussi is certainly present in GRIP and it also ranges from the early to the late Turolian; its possible Vallesian occurrence needs confirmation. The other two late Miocene chalicotheres of GRIP A. macedonicus and Kalimantsia bulgarica are restricted to the Turolian of the Balkan Peninsula.     

Arabidopsis thaliana Chromosome 4 Replicates in Two Phases That Correlate with Chromatin State

DNA replication programs have been studied extensively in yeast and animal systems, where they have been shown to correlate with gene expression and certain epigenetic modifications. Despite the conservation of core DNA replication proteins, little is known about replication programs in plants. We used flow cytometry and tiling microarrays to profile DNA replication of Arabidopsis thaliana chromosome 4 (chr4) during early, mid, and late S phase. Replication profiles for early and mid S phase were similar and encompassed the majority of the euchromatin. Late S phase exhibited a distinctly different profile that includes the remaining euchromatin and essentially all of the heterochromatin. Termination zones were consistent between experiments, allowing us to define 163 putative replicons on chr4 that clustered into larger domains of predominately early or late replication. Early-replicating sequences, especially the initiation zones of early replicons, displayed a pattern of epigenetic modifications specifying an open chromatin conformation. Late replicons, and the termination zones of early replicons, showed an opposite pattern. Histone H3 acetylated on lysine 56 (H3K56ac) was enriched in early replicons, as well as the initiation zones of both early and late replicons. H3K56ac was also associated with expressed genes, but this effect was local whereas replication time correlated with H3K56ac over broad regions. The similarity of the replication profiles for early and mid S phase cells indicates that replication origin activation in euchromatin is stochastic. Replicon organization in Arabidopsis is strongly influenced by epigenetic modifications to histones and DNA. The domain organization of Arabidopsis is more similar to that in Drosophila than that in mammals, which may reflect genome size and complexity. The distinct patterns of association of H3K56ac with gene expression and early replication provide evidence that H3K56ac may be associated with initiation zones and replication origins.