TLR4 expression and functionality are downregulated in glioblastoma cells and in tumor-associated macrophages: A new mechanism of immune evasion?

Glioblastoma (GB) is the most common and aggressive form of primary brain tumor, in which the presence of an inflammatory environment, composed mainly by tumor-associated macrophages (TAMs), is related to its progression and development of chemoresistance. Toll-Like Receptors (TLRs) are key components of the innate immune system and their expression in both tumor and immune-associated cells may impact the cell communication in the tumor microenvironment (TME), further modeling cancer growth and response to therapy. Here, we investigated the participation of TLR4-mediated signaling as a mechanism of induced-immune escape in GB. Initially, bioinformatics analysis of public datasets revealed that TLR4 expression is lower in GB tumors when compared to astrocytomas (AST), and in a subset of TAMs. Further, we confirmed that TLR4 expression is downregulated in chemoresistant GB, as well as in macrophages co-cultured with GB cells. Additionally, TLR4 function is impaired in those cells even following stimulation with LPS, an agonist of TLR4. Finally, experiments performed in a cohort of clinical primary and metastatic brain tumors indicated that the immunostaining of TLR4 and CD45 are inversely proportional, and confirmed the low TLR4 expression in GBs. Interestingly, the cytoplasmic/nuclear pattern of TLR4 staining in cancer tissues suggests additional roles of this receptor in carcinogenesis. Overall, our data suggest the downregulation of TLR4 expression and activity as a strategy for GB-associated immune escape. Additional studies are necessary to better understand TLR4 signaling in TME in order to improve the benefits of immunotherapy based on TLR signaling.

Predicting the fate of basketball throws: an EEG study on expert action prediction in wheelchair basketball players.

The ability to anticipate and detect changes in human movement helps people to modify their behaviors in ever changing environments. Studies indicate that expertise modulates observation of domain-specific actions in sports-a process that is crucial for adapting rapidly to a new situation, often before awareness of environmental changes is achieved. Here, we explored the electrophysiological underpinnings of wheelchair basketball players predicting the fate of free throws performed by wheelchair basketball athletes. We performed electroencephalography (EEG) in semi-professional wheelchair players with different degrees of expertise (players) and in ambulant, non-expert people (controls) while they observed movie stimuli of a free throw that could land inside or outside the basket. On each trial, participants were asked to predict the outcome of the throw. For each group, event-related potentials (ERPs) were averaged as a function of condition, using only the trials that were correctly predicted. Results show that compared to controls, expert players exhibit a greater negative amplitude of oCNV over Pz (an observational contingent negative variation-like waveform which is considered a marker of action effect prediction) during the wrist movement preceding the ball release (the last 100 ms of the shot), which carries the most crucial kinematic information regarding the fate of the throw. Our data provide further support to the view that functional modulation of the action observation network is associated with expertise.

Action anticipation beyond the action observation network: a functional magnetic resonance imaging study in expert basketball players.

The ability to predict the actions of others is quintessential for effective social interactions, particularly in competitive contexts (e.g. in sport) when knowledge about upcoming movements allows anticipating rather than reacting to opponents. Studies suggest that we predict what others are doing by using our own motor system as an internal forward model and that the fronto-parietal action observation network (AON) is fundamental for this ability. However, multiple-duty cells dealing with action perception and execution have been found in a variety of cortical regions. Here we used functional magnetic resonance imaging to explore, in expert basketball athletes and novices, whether the ability to make early predictions about the fate of sport-specific actions (i.e. free throws) is underpinned by neural regions beyond the classical AON. We found that, although involved in action prediction, the fronto-parietal AON was similarly activated in novices and experts. Importantly, athletes exhibited relatively greater activity in the extrastriate body area during the prediction task, probably due to their expert reading of the observed action kinematics. Moreover, experts exhibited higher activation in the bilateral inferior frontal gyrus and in the right anterior insular cortex when producing errors, suggesting that they might become aware of their own errors. Correct action prediction induced higher posterior insular cortex activity in experts and higher orbito-frontal activity in novices, suggesting that body awareness is important for performance monitoring in experts, whereas novices rely more on higher-order decision-making strategies. This functional reorganization highlights the tight relationship between action anticipation, error awareness and motor expertise leading to body-related processing and differences in decision-making processes.

The prevalence of acne in the north of Portugal.

BACKGROUND: Acne is a disease that affects almost all teenagers (60-90%), and it is the pathology exhibiting the highest morbidity in the 10-24 year-olds age group. There are no consistent data at national level by which we can evaluate the preponderance of this pathology in the Portuguese population. OBJECTIVE: To estimate the prevalence of acne in teenage school students (10-12 year-olds). STUDY DESIGN: A study was carried out involving all 8 regions in the north of Portugal. One school per region was selected at random. RESULTS: As expected, the figure we obtained for the prevalence of this pathology was high (82.4%) with males being the most affected. Nevertheless, only 44% of the affected treated their acne, although the face is the part of the body most affected. In the females high androgenization (which is manifested by the presence of hair on the upper lip and on the side of the face) doubles the median of the degree of acne registered. Regional asymmetry was found in relation to information about the disorder. The degrees of acne are higher in schools in the interior. In the more rural areas, the pharmacist still plays an important role in prescribing treatment. CONCLUSION: As a rule, individuals are correctly informed about acne, confirming that the search for treatment and awareness of its value are generally helping to gradually eliminate some of the stigmas from the past.

Níveis séricos da penicilina G benzatina após administração intramuscular / Serum levels of benzathine penicillin G after intramuscular administration

Foi realizado estudo farmacocinetico da penicilina G benzatina, apos injecao intramuscular em adultos normais, utilizando-se a tecnica microbiologica da penicilina residual. O metodo mostrou-se sensivel (0,005U/ml), reprodutivel (95%) e linear no intervalo de estudo entre 0,005 e 0,l00 U/ml soro. Apos injecao de 1.200.000 U, os niveis sericos obtidos (U/ml) foram: 0,110 +/- 0,19 (1a. hora); 0,081 +/- 0,010 (24a. hora); 0,074 +/- 0,006 (48a. hora); 0,072 +/- 0,006 (72a. hora); 0,071 +/- 0,005 (7o. dia); 0,037 +/- 0,003 (14o.dia); 0,031 +/- 0,001 (21o. dia) e 0,021 +/- 0,001 (28o. dia). Encontraram-se niveis eficazes (0,03 U/ml) para profilaxia da doenca reumatica em 100% dos individuos ate o 7o. dia e em 77%, em 70% e em 15% dos casos ate 14, 21 e 28 dias respectivamente. A lenta liberacao da penicilina benzatina do sitio de aplicacao foi comprovada pelas taxas de absorcao de 39,7 +/- 4,9% (0-7 dias) , de 29,9 +/- 6,5% (7-14 dias), de 18,8 +/- 5,1% (14-21 dias) e de 14,9 +/- 4,5% (21-28 dias).O tempo de meia-vida de eliminacao do antibiotico variou entre 15 +/- 1,5 dias. O pequeno valor da constante de eliminacao sugeriu lento desaparecimento da penicilina no compartimento central