Decision making and management of gliomas: practical considerations

Over the last decade, diagnostic options and introduction of novel treatments have expanded the armamentarium in the management of malignant glioma. Combined chemoradiotherapy has become the standard of care in glioblastoma up to the age of 70 years, while treatment in elderly patients or with lower grade glioma is less well defined. Molecular markers define different disease subtypes and allow for adapted treatment selection. This review focuses on simple questions arising in the daily management of patient

The Impact of the African Great Lakes on the Regional Climate

Although the African Great Lakes are important regulators for the East African climate, their influence on atmospheric dynamics and the regional hydrological cycle remains poorly understood. This study aims to assess this impact by comparing a regional climate model simulation that resolves individual lakes and explicitly computes lake temperatures to a simulation without lakes. The Consortium for Small-Scale Modelling model in climate mode (COSMO-CLM) coupled to the Freshwater Lake model (FLake) and Community Land Model (CLM) is used to dynamically downscale a simulation from the African Coordinated Regional Downscaling Experiment (CORDEX-Africa) to 7-km grid spacing for the period of 1999–2008. Evaluation of the model reveals good performance compared to both in situ and satellite observations, especially for spatiotemporal variability of lake surface temperatures (0.68-K bias), and precipitation (−116 mm yr−1 or 8% bias). Model integrations indicate that the four major African Great Lakes almost double the annual precipitation amounts over their surface but hardly exert any influence on precipitation beyond their shores. Except for Lake Kivu, the largest lakes also cool the annual near-surface air by −0.6 to −0.9 K on average, this time with pronounced downwind influence. The lake-induced cooling happens during daytime, when the lakes absorb incoming solar radiation and inhibit upward turbulent heat transport. At night, when this heat is released, the lakes warm the near-surface air. Furthermore, Lake Victoria has a profound influence on atmospheric dynamics and stability, as it induces circular airflow with over-lake convective inhibition during daytime and the reversed pattern at night. Overall, this study shows the added value of resolving individual lakes and realistically representing lake surface temperatures for climate studies in this region

Immunoregulation of Dendritic Cell Subsets by Inhibitory Receptors in Urothelial Cancer.

Blockade of inhibitory receptors (IRs) overexpressed by T cells can activate antitumor immune responses, resulting in the most promising therapeutic approaches, particularly in bladder cancer, currently able to extend patient survival. Thanks to their ability to cross-present antigens to T cells, dendritic cells (DCs) are an immune cell population that plays a central role in the generation of effective antitumor T-cell responses. While IR function and expression have been investigated in T cells, very few data are available for DCs. Therefore, we analyzed whether DCs express IRs that can decrease their functions. To this end, we investigated several IRs (PD-1, CTLA-4, BTLA, TIM-3, and CD160) in circulating CD1c javax.xml.bind.JAXBElement@4f1331d4 DCs, CD141 javax.xml.bind.JAXBElement@68e4feef DCs, and plasmacytoid DCs from healthy donors and patients with urothelial cancer (UCa). Different DC subsets expressed BTLA and TIM-3 but not other IRs. More importantly, BTLA and TIM-3 were significantly upregulated in DCs from blood of UCa patients. Locally, bladder tumor-infiltrating DCs also overexpressed BTLA and TIM-3 compared to DCs from paired nontumoral tissue. Finally, in vitro functional experiments showed that ligand-mediated engagement of BTLA and TIM-3 receptors significantly reduced the secretion of effector cytokines by DC subpopulations. Our findings demonstrate that UCa induces local and systemic overexpression of BTLA and TIM-3 by DCs that may result in their functional inhibition, highlighting these receptors as potential targets for UCa treatment. We investigated the expression and function of a panel of inhibitory receptors in dendritic cells (DCs), an immune cell subpopulation critical in initiation of protective immune responses, among patients with urothelial carcinoma. We found high expression of BTLA and TIM-3 by blood and tumor DCs, which could potentially mediate decreased DC function. The results suggest that BTLA and TIM-3 might be new targets for urothelial carcinoma treatment

First report of Rhabdias (Nematoda: Rhabdiasoidea) from lungs of montane chameleons in Cameroon: description of two new species and notes on biology.

Les nematodes pulmonaires parasites de cameleons du genre Rhabdias n'etaient connus qu'en Afrique orientale et a Madagascar. Deux especes sont decrites au Cameroun: il Rhabdias okuensis n. sp., hote-type Chamaeleo (Trioceros) quadricornis gracilior au Mont Oku est frequent; l'espece est proche de R. jarki, au Burundi, par la capsule buccale courte et l'oesophage long et mince, et en est distincte par la grande vesicule cervicale et des caracteres cephaliques (bouche, papilles). Les femelles parasites sont hermaphrodites (spermatozoides identifies); en outre, elles perforent la paroi pulmonaire et provoquent des lesions, comme R. jarki. C. (T.) w. wiedersheimi au Mont Oku heberge aussi R. okuensis, comme cela est demontre par les sequences des genes 12S rADN et coxl. ii) R. cristati n. sp., hote-type C. (T.) cristatus ou Mont Cameroun est decrit chez un specimen fortement parasite; l'espece est proche de R. chamaeleonis d'Afrique Orientale, et en est distinct par la grande taille de la capsule buccale et l'apex epais de l'intestin. La phase libre du cycle, etudiee chez R. okuensis, presente les caracteres des autres Rhobdias de cameleons: heterogonie, developpement des larves par endotokie matricide, stade infectant avec une extremite caudale epaisse et arrondie, exuvie transformee en gaine cuticulaire epaisse; chaque femelle libre produit une larve, comme chez les autres Rhabdias africains, alors que la femelle de R. gemellipara, parasite de cameleon malgache, en produit deux

Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study

Background Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter. Methods Overall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2×/wk; n = 88), intensive cilengitide (2000 mg 5×/wk during wk 1−6, thereafter 2×/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 1−6), followed by TMZ maintenance therapy (TMZ/RT→TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability. Results Median overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P = .3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated. Conclusions Standard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II stud

Wernicke's region--where is it

In this subject, the first question both logically and chronologically was and is: Can a lesion (focal damage) of the cerebrum cause a loss of language without causing a loss of intelligence? That is the original question, still debated hotly by many people. Much of the heat is attributable to the way in which the question is phrased. Suppose we phrase it relatively, as follows: Can a lesion of the cerebrum produce a deficit in language that is far in excess of the concomitant deficit in intelligence? Asked in this way, almost everyone would answer yes. There are worthy persons who are still arguing that anyone who has a loss of language from a cerebral lesion must have some accompanying loss of intelligence. Similarly, there are equally worthy persons recurrently showing us that intelligence can be preserved in spite of severe aphasia. Both parties are undoubtedly correct. But the force of either argument is largely dissipated when the question is rephrased in the relative way. Of course, how much intelligence is lost (or retained) depends upon how one goes about measuring intelligence; but with almost any measures, except those strictly linguistic, the answer will be yes. Indeed, if the answer were not yes, there would not be such a thing a

Automated database-guided expert-supervised orientation for immunophenotypic diagnosis and classification of acute leukemia

Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated. Depending on the database-guided results, patients were categorized as: (i) typical T, B or Myeloid without or; (ii) with a transitional component to another lineage; (iii) atypical; or (iv) mixed-lineage. Using this automated algorithm, in 781/783 cases (99.7%) the right panel was selected, and data comparable to the final WHO-diagnosis was already provided in >93% of cases (85% T-ALL, 97% BCP-ALL, 95% AML and 87% mixed-phenotype AL patients), even without data on the full-characterization panels. Our results show that database-guided analysis facilitates standardized interpretation of ALOT results and allows accurate selection of the relevant classification panels, hence providing a solid basis for designing future WHO AL classifications

Diminutive, degraded but dissimilar: <i>Wolbachia</i> genomes from filarial nematodes do not conform to a single paradigm.

Wolbachia are alpha-proteobacteria symbionts infecting a large range of arthropod species and two different families of nematodes. Interestingly, these endosymbionts are able to induce diverse phenotypes in their hosts: they are reproductive parasites within many arthropods, nutritional mutualists within some insects and obligate mutualists within their filarial nematode hosts. Defining Wolbachia 'species' is controversial and so they are commonly classified into 17 different phylogenetic lineages, termed supergroups, named A-F, H-Q and S. However, available genomic data remain limited and not representative of the full Wolbachia diversity; indeed, of the 24 complete genomes and 55 draft genomes of Wolbachia available to date, 84 % belong to supergroups A and B, exclusively composed of Wolbachia from arthropods. For the current study, we took advantage of a recently developed DNA-enrichment method to produce four complete genomes and two draft genomes of Wolbachia from filarial nematodes. Two complete genomes, wCtub and wDcau, are the smallest Wolbachia genomes sequenced to date (863 988 bp and 863 427 bp, respectively), as well as the first genomes representing supergroup J. These genomes confirm the validity of this supergroup, a controversial clade due to weaknesses of the multilocus sequence typing approach. We also produced the first draft Wolbachia genome from a supergroup F filarial nematode representative (wMhie), two genomes from supergroup D (wLsig and wLbra) and the complete genome of wDimm from supergroup C. Our new data confirm the paradigm of smaller Wolbachia genomes from filarial nematodes containing low levels of transposable elements and the absence of intact bacteriophage sequences, unlike many Wolbachia from arthropods, where both are more abundant. However, we observe differences among the Wolbachia genomes from filarial nematodes: no global co-evolutionary pattern, strong synteny between supergroup C and supergroup J Wolbachia, and more transposable elements observed in supergroup D Wolbachia compared to the other supergroups. Metabolic pathway analysis indicates several highly conserved pathways (haem and nucleotide biosynthesis, for example) as opposed to more variable pathways, such as vitamin B biosynthesis, which might be specific to certain host-symbiont associations. Overall, there appears to be no single Wolbachia-filarial nematode pattern of co-evolution or symbiotic relationship

Attention modulates motor system activation during action observation: evidence for inhibitory rebound

Perceiving another individual’s actions activates the human motor system. We investigated whether this effect is stronger when the observed action is relevant to the observer’s task. The mu rhythm (oscillatory activity in the 8- to 13-Hz band over sensorimotor cortex) was measured while participants watched videos of grasping movements. In one of two conditions, the participants had to later report how many times they had seen a certain kind of grasp. In the other condition, they viewed the identical videos but had to later report how many times they had seen a certain colour change. The colour change and the grasp always occurred simultaneously. Results show mu rhythm attenuation when watching the videos relative to baseline. This attenuation was stronger when participants later reported the grasp rather than the colour, suggesting that the motor system is more strongly activated when the observed grasping actions were relevant to the observer’s task. Moreover, when the graspable object disappeared after the offset of the video, there was subsequent mu rhythm enhancement, reflecting a post-stimulus inhibitory rebound. This enhancement was again stronger when making judgments about the grasp than the colour, suggesting that the stronger activation is followed by a stronger inhibitory rebound