• Carstens Garrett posted an update 6 months, 2 weeks ago

    Different mechanisms as post-transcriptional events, epigenetics factors or protein function may be involved.

    mRNA expression is not useful as a predictor factor for the prognosis and severity of the disease. Different mechanisms as post-transcriptional events, epigenetics factors or protein function may be involved.Cerebral computed tomography angiography is a widely available imaging technique that helps in the diagnosis of vascular pathologies. Contrast administration is needed to accurately assess the arteries. On non-contrast computed tomography, arteries are hardly distinguishable from the brain tissue, therefore, radiologists do not consider this imaging modality appropriate for the evaluation of vascular pathologies. There are known contraindications to administering iodinated contrast media, and in these cases, the patient has to undergo another examination to visualize cerebral arteries, such as magnetic resonance angiography. Deep learning for image segmentation has proven to perform well on medical data for a variety of tasks. The aim of this research was to apply deep learning methods to segment cerebral arteries on non-contrast computed tomography scans and consequently, generate angiographies without the need for contrast administration. The dataset for this research included 131 patients who underwent brain non-contrast computed tomography directly followed by computed tomography with contrast administration. Then, the segmentations of arteries were generated and aligned with non-contrast computed tomography scans. A deep learning model based on the U-net architecture was trained to perform the segmentation of blood vessels on non-contrast computed tomography. An evaluation was performed on separate test data, as well as using cross-validation, reaching Dice coefficients of 0.638 and 0.673, respectively. see more This study proves that deep learning methods can be leveraged to quickly solve problems that are difficult and time-consuming for a human observer, therefore providing physicians with additional information on the patient. To encourage the further development of similar tools, all code used for this research is publicly available.

    Immunoglobulin A Nephropathy (IgAN) is the most common type of glomerulonephritis with variable renal outcome. The association between IgAN and patient survival is limited. The effect of crescents on patient survival was never studied.

    We conducted a retrospective cohort study between January 2003 and December 2013. All patients with the biopsy-proved IgAN was enrolled for the analysis of patient survival and renal survival. Cox regression model was used analyze the associated factors for patient survival.

    All 388 participants with IgAN were enrolled, in which 45 patients with crescents. The mean percentage of glomeruli involvement was 23±18.9%. After long-term follow-up, crescents group had both worse renal (p = 0.034) and patient survivals (p = 0.016). In univariate Cox regression model, the age (HR = 1.08, 95% CI = 1.05-1.12, p<0.001), crescents (HR = 3.93, 95% CI = 1.18-13.07, p = 0.025), serum albumin (HR = 0.023, 95%CI = 0.11-0.50, p<0.001), blood total protein (HR = 0.46, 95%CI = 0.28-0.75, more careful to care patients with crescents IgAN.Each year, 4.3 million pregnant women are exposed to malaria risk in Latin America and the Caribbean. Plasmodium vivax causes 76% of the regional malaria burden and appears to be less affected than P. falciparum by current elimination efforts. This is in part due to the parasite’s ability to stay dormant in the liver and originate relapses within months after a single mosquito inoculation. Primaquine (PQ) is routinely combined with chloroquine (CQ) or other schizontocidal drugs to supress P. vivax relapses and reduce the risk of late blood-stage recrudescences of parasites with low-grade CQ resistance. However, PQ is contraindicated for pregnant women, who remain at increased risk of repeated infections following CQ-only treatment. Here we apply a mathematical model to time-to-recurrence data from Juruá Valley, Brazil’s main malaria transmission hotspot, to quantify the extra burden of parasite recurrences attributable to PQ ineligibility in pregnant women. The model accounts for competing risks, since relapsconclude that post-treatment CQ prophylaxis could be further explored as a measure to prevent vivax malaria recurrences in pregnancy and avert their adverse effects on maternal and neonatal health.Mitochondrial translation defects can be due to mutations affecting mitochondrial- or nuclear-encoded components. The number of known nuclear genes involved in mitochondrial translation has significantly increased in the past years. RCC1L (WBSCR16), a putative GDP/GTP exchange factor, has recently been described to interact with the mitochondrial large ribosomal subunit. In humans, three different RCC1L isoforms have been identified that originate from alternative splicing but share the same N-terminus, RCC1LV1, RCC1LV2 and RCC1LV3. All three isoforms were exclusively localized to mitochondria, interacted with its inner membrane and could associate with homopolymeric oligos to different extent. Mitochondrial immunoprecipitation experiments showed that RCC1LV1 and RCC1LV3 associated with the mitochondrial large and small ribosomal subunit, respectively, while no significant association was observed for RCC1LV2. Overexpression and silencing of RCC1LV1 or RCC1LV3 led to mitoribosome biogenesis defects that resulted in decreased translation. Indeed, significant changes in steady-state levels and distribution on isokinetic sucrose gradients were detected not only for mitoribosome proteins but also for GTPases, (GTPBP10, ERAL1 and C4orf14), and pseudouridylation proteins, (TRUB2, RPUSD3 and RPUSD4). All in all, our data suggest that RCC1L is essential for mitochondrial function and that the coordination of at least two isoforms is essential for proper ribosomal assembly.This study aimed to establish and reproduce transgenic pigs expressing human growth hormone (hGH) in their milk. We also aimed to purify hGH from the milk, to characterize the purified protein, and to assess the potential of our model for mass production of therapeutic proteins using transgenic techniques. Using ~15.5 L transgenic pig milk, we obtained proteins with ≥ 99% purity after three pre-treatments and five column chromatography steps. To confirm the biosimilarity of our milk-derived purified recombinant hGH (CGH942) with commercially available somatropin (Genotropin), we performed spectroscopy, structural, and biological analyses. We observed no difference between the purified protein and Genotropin samples. Furthermore, rat models were used to assess growth promotion potential. Our results indicate that CGH942 promotes growth, by increasing bone development and body weight. Toxicity assessments revealed no abnormal findings after 4 weeks of continuous administration and 2 weeks of recovery. The no-observed-adverse-effect level for both males and females was determined to be 0.

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