Gene analysis in patients with premature ovarian failure or gonadal dysgenesis: a preliminary study

OBJECTIVE: The aim of this study was to evaluate the presence of mutations in the coding region of the QM gene and fragile X in patients with premature ovarian failure and gonadal dysgenesis. METHODS: After approval by the local Ethics Committee, blood samples, in EDTA, of 100 normally ovulating women, 23 with premature ovarian failure (POF) and 14 with gonadal dysgenesis 46XX, aged less than 40 years, were screened for mutation in the QM gene coding region. All patients with POF have 46, XX karyotype and serum levels of follicle-stimulating hormone (FSH) over 30 mIU/mL. In addition, all samples from patients with premature ovarian failure underwent analysis for fragile X. RESULTS: The QM gene located at a hotspot region (Xq28) showed five points of mutations in a patient with premature ovarian failure. Four of them were able to change the amino acid sequence of the protein. None of our patients were diagnosed as having pre or mutant X fragile syndrome. CONCLUSION: Our study suggests that Xq28 (QM gene) may be involved in ovary failure. However, further studies are needed to confirm this hypothesis.     

Absorption spectroscopy of EBT model GAFCHROMIC film

The introduction of radiochromic films has solved some of the problems associated with conventional 2D radiation detectors. Their high spatial resolution, low energy dependence, and near-tissue equivalence make them ideal for measurement of dose distributions in radiation fields with high dose gradients. Precise knowledge of the absorption spectra of these detectors can help to develop more suitable optical densitometers and potentially extend the use of these films to other areas such as the measurement of the radiation beam spectral information. The goal of this study is to present results of absorption spectra measurements for the new GAFCHROMIC film, EBT type, exposed to 6 MV photon beam in the dose range from 0 to 6 Gy. Spectroscopic analysis reveals that in addition to the two main absorption peaks, centered at around 583 and 635 nm, the absorption spectrum in the spectral range from 350 to 800 nm contains six more absorption bands. Comparison of the absorption spectra reveals that previous HD-810, MD-55, as well as HS GAFCHROMIC film models, have nearly the same sensitive layer base material, whereas the new EBT model, GAFCHROMIC film has a different composition of its sensitive layer. We have found that the two most prominent absorption bands in EBT model radiochromic film do not change their central wavelength position with change in a dose deposited to the film samples.     

Dose calculation formalisms and consensus dosimetry parameters for intravascular brachytherapy dosimetry: recommendations of the AAPM Therapy Physics Committee Task Group No. 149

Since the publication of AAPM Task Group 60 report in 1999, a considerable amount of dosimetry data for the three coronary brachytherapy systems in use in the United States has been reported. A subgroup, Task Group 149, of the AAPM working group on Special Brachytherapy Modalities (Bruce Thomadsen, Chair) was charged to develop recommendations for dose calculation formalisms and the related consensus dosimetry parameters. The recommendations of this group are presented here. For the Cordis 192Ir and Novoste 90Sr/90Y systems, the original TG-43 formalism in spherical coordinates should be used along with the consensus values of the dose rate constant, geometry function, radial dose function, and anisotropy function for the single seeds. Contributions from the single seeds should be added linearly for the calculation of dose distributions from a source train. For the Guidant 32P wire system, the modified TG-43 formalism in cylindrical coordinates along with the recommended data for the 20 and 27 mm wires should be used. Data tables for the 6, 10, 14, 18, and 22 seed trains of the Cordis system, 30, 40, and 60 mm seed trains of the Novoste system, and the 20 and 27 mm wires of the Guidant system are presented along with our rationale and methodology for selecting the consensus data. Briefly, all available datasets were compared with each other and the consensus dataset was either an average of available data or the one obtained from the most densely populated study; in most cases this was a Monte Carlo calculation.     

Behavioral and neural responses to gustatory stimuli delivered non-contingently through intra-oral cannulas

The act of eating requires a decision by an animal to place food in its mouth. The reasons to eat are varied and include hunger as well as the food's expected reward value. Previous studies of tastant processing in the rat primary gustatory cortex (GC) have used either anesthetized or awake behaving preparations that yield somewhat different results. Here we have developed a new preparation in which we explore the influences of intra-oral and non-contingent tastant delivery on rats' behavior and on their GC neural responses. We recorded single-unit activity in the rat GC during two sequences of tastant deliveries, PRE and POST, which were separated by a waiting period. Six tastants ranging in hedonic value from sucrose to quinine were delivered in the first two protocols called 4TW and L-S. In the third one, the App L-S protocol, only hedonically positive tastants were used. In the 4TW protocol, tastants were delivered in blocks whereas in the two L-S protocols tastants were randomly interleaved. In the 4TW and L-S protocols the probability of ingesting tastants in the PRE sequence decreased exponentially with the trial number. Moreover, in both protocols this decrease was greater in the POST than in the PRE sequence likely because the subjects learned that unpleasant tastants were to be delivered. In the App L-S protocol the decrease in ingestion was markedly slower than in the other protocols, thus supporting the hypothesis that the decrease in appetitive behavior arises from the non-contingent intra-oral delivery of hedonically negative tastants like quinine. Although neuronal responses in the three protocols displayed similar variability levels, significant differences existed between the protocols in the way the variability was partitioned between chemosensory and non-chemosensory neurons. While in the 4TW and L-S protocols the former population displayed more changes than the latter, in the App L-S protocol variability was homogeneously distributed between the two populations. We posit that these tuning changes arise, at least in part, from compounds released upon ingestion, and also from differences in areas of the oral cavity that are bathed as the animals ingest or reject the tastants.     

Prognostic significance of p53 and p63 immunolocalisation in primary and matched lymph node metastasis in oral squamous cell carcinoma

This study evaluates the prognostic significance of p53 and p63 immunolocalisation in oral squamous cell carcinoma samples from 45 matched primary tumors (PT) and lymph node metastases (LNM). Data regarding patient age, gender, primary site, histological differentiation, metastasis, disease-free survival (DFS) and overall survival (OS) were available. p53 and p63 immunolabeling was detected in 17 (37.8%) and 23 (51.1%) of the PT, respectively. For LNM, there was p53 and p63 labeling in 23 (51.1%) and 26 (57.8%) cases, respectively. Most cases showed similar labeling in PT and the corresponding LNM (73.3% for p53 and 53.3% for p63, respectively). No statistically significant associations were found between p53 and p63 immunolabeling and histological differentiation; p63 positive tumors showed higher DFS (p=0.006) and OS (p=0.049); and p53-negative tumors had a higher DFS interval (p=0.009). Our findings suggest that initially p53-negative tumors and initially p63-positive tumors that retain this labeling pattern may follow less aggressive biological courses and present better prognoses.     

The role of macrophage migration inhibitory factor in the cascade of events leading to reperfusion-induced inflammatory injury and lethality

Ischemia and reperfusion (I/R) injury is associated with a systemic inflammatory response, characterized by intense tumor necrosis factor (TNF)-alpha production and TNF-alpha-dependent tissue injury. Macrophage migration inhibitory factor (MIF) is a potent proinflammatory cytokine that may induce TNF-alpha release and play an important role in innate immune and inflammatory responses. The aim of this work was to assess whether MIF was involved the inflammatory cascade and injury that follows intestinal I/R. To this end, wild-type (WT) and MIF-deficient (MIF(-/-)) mice underwent 60 minutes of ischemia followed by 60 minutes of reperfusion, after which they were culled for the assessment of inflammatory parameters. I/R was accompanied by an increase in circulating levels of MIF and an increase of vascular permeability, hemorrhage, and production of TNF-alpha in the intestine and lungs. The latter parameters were markedly suppressed in reperfused MIF(-/-) mice, and this was associated with decreased lethality (80% in WT versus 20% in MIF(-/-) mice). Interestingly, the reperfusion-associated neutrophil accumulation in the intestine and lungs was similar in WT and MIF(-/-) mice. Leukocytes isolated from lungs of MIF(-/-) mice were less activated, as assessed by their response to zymosan in a luminol-enhanced chemiluminescence assay. In conclusion, our results suggest that MIF plays an important role in the cascade of events leading to TNF-alpha production and reperfusion-induced tissue injury and lethality in mice.     

Fas ligand-dependent inflammatory regulation in acute myocarditis induced by Trypanosoma cruzi infection

Fas/Fas ligand (Fas-L) engagement, a potent inducer of apoptosis, is also important for cellular activation, regulation of effector and chemotactic activity, and secretion of chemokines and cytokines. We evaluated the relevance of Fas/Fas-L in the regulation of myocarditis induced by Trypanosoma cruzi infection and observed that in Fas-L(-/-) mice (gld/gld), cardiac infiltration was significantly reduced, accordingly showing less cardiomyocyte destruction. Fluorescence-activated cell sorting analysis of cardiac inflammatory cells showed higher numbers of CD8(+) T cells in BALB/c compared with gld/gld mice but similar levels of lymphocyte function-associated antigen-1, intercellular adhesion molecule, CD2, and CD69 expression; MAC-1(+) myeloid cells and mast cells were increased in BALB/c mice, whereas gld/gld mice exhibited an enrichment of CD4(+/low) T cells. Intracellular labeling of cytokines revealed no clear cardiac skewing of Th1 or Th2 responses, but we found a higher number of interleukin-10(+) cells in gld/gld mice and a deficient expression of vascular cell adhesion molecule-1 on cardiac endothelial cells in gld/gld mice. Finally, we found a population of CD3(+) but CD4/CD8 double negative cardiac T cells in both groups of infected mice, but down-regulation of some adhesion molecules and surface receptors was only observed in gld/gld mice, indicating a targeted T-cell population mostly affected by the lack of Fas-L engagement. These results point to a role for myocarditis regulation by Fas/Fas-L beyond its possible direct relevance in cellular death.     

Polycyclic aromatic hydrocarbon patterns in the city of Rio de Janeiro

In this study, the concentrations of 16 Polycyclic Aromatic Hydrocarbon (PAH), considered priority by US EPA (US Environmental Protection Agency), in fine particulate matter (PM_2.5), were determined in a forest reserve and in an urban area in the city of Rio de Janeiro. The PM_2.5 samples were collected in the Tijuca Forest (TF) and on the Maracanã campus of the State University of Rio de Janeiro (UERJ), using PM_2.5 high-volume air samplers, from November 2015 to April 2016. The organic matter was extracted, separated by liquid chromatography, and analyzed by gas chromatography-mass spectrometry (GC-MS). The mean total PAH (excluding naphthalene, acenaphthene, and acenaphthylene) concentrations were 0.46?±?0.61 ng m^?3 and 1.12?±?0.71 ng m^?3 in PM_2.5 collected at TF and UERJ, respectively. The diagnostic ratios suggested vehicular sources for both sites with no clear distinction between light and heavy vehicular sources. Cluster and principal component analyses were also used to clarify the possible PAH sources. Simulations of air mass trajectories confirmed the transport of pollutants from the city to the forest. Mutagenicity tests revealed that the PM collected in the UERJ presented mutagenic positive activity, likely for nitro-PAH and amino-PAH, which may be related to vehicular emissions. For the TF, although the forest was impacted by the pollutants, no positive activity was detected. Correlation and cluster analyses showed different PAH distributions for the TF and UERJ sites, which indicates that the TF receives the air masses from the city but is also impacted by local emissions.     

A Nutritional Perspective of Ketogenic Diet in Cancer: A Narrative Review

The predominant use of glucose anaerobically by cancer cells (Warburg effect) may be the most important characteristic the majority of these cells have in common and, therefore, a potential metabolic pathway to be targeted during cancer treatment. Because this effect relates to fuel oxidation, dietary manipulation has been hypothesized as an important strategy during cancer treatment. As such, the concept of a ketogenic diet (KD) in cancer emerged as a metabolic therapy (ie, targeting cancer cell metabolism) rather than a dietary approach. The therapeutic mechanisms of action of this high-fat, moderate-to-low protein, and very-low-carbohydrate diet may potentially influence cancer treatment and prognosis. Considering the lack of a dietetics-focused narrative review on this topic, we compiled the evidence related to the use of this diet in humans with diverse cancer types and stages, also focusing on the nutrition and health perspective. The use of KD in cancer shows potentially promising, but inconsistent, results. The limited number of studies and differences in study design and characteristics contribute to overall poor quality evidence, limiting the ability to draw evidence-based conclusions. However, the potential positive influences a KD may have on cancer treatment justify the need for well-designed clinical trials to better elucidate the mechanisms by which this dietary approach affects nutritional status, cancer prognosis, and overall health. The role of registered dietitian nutritionists is demonstrated to be crucial in planning and implementing KD protocols in oncology research settings, while also ensuring patients’ adherence and optimal nutritional status.