• Blum Hickman opublikował 1 rok, 3 miesiące temu

    ere acquired or resulted from diversification in function of other genes. • Substrate specificity of plant glucosyltransferases could drive trichothecene diversity.J. Marion Sims (1813-1883) is often regarded as the founder of modern surgical gynecology. Widely known and respected during his lifetime, he was honored after death with a statue erected in New York City’s Bryant Park. It was later relocated to Central Park, where it remained until 2018, when it was removed after persistent public protests over its presence. The controversy arose over perceptions of Sims’s most famous achievement the development of the first reliable surgical cure for vesico-vaginal fistula, a catastrophic complication of prolonged obstructed labor, which was common in the nineteenth century. Sims developed his surgical technique by operating on a group of enslaved African-American women with fistulas between 1846 and 1849. Modern attacks on Sims are based more on a presentist revulsion over the institution of slavery than on a clear understanding of what Sims actually did within the context of his time and place. Modern critics attack his „experimental” surgeries, the patients’ lack of „informed consent,” and Sims’s failure to use anesthesia during fistula surgery. None of these criticisms takes into consideration the appalling nature of the injuries these women had received, the suffering their condition caused them, the lack of any effective „standard-of-care” treatment for fistulas at that time, the social and legal constraints facing doctors who treated slaves, or the uncertain and problematic early history of anesthesiology. Although „retrospective indignation” may be emotionally satisfying, it does not illuminate the past nor help us understand difficult decision-making in surgery, whatever the time or place.Groundnut has entered now in post-genome era enriched with optimum genomic and genetic resources to facilitate faster trait dissection, gene discovery and accelerated genetic improvement for developing climate-smart varieties. Cultivated groundnut or peanut (Arachis hypogaea), an allopolyploid oilseed crop with a large and complex genome, is one of the most nutritious food. This crop is grown in more than 100 countries, and the low productivity has remained the biggest challenge in the semiarid tropics. Recently, the groundnut research community has witnessed fast progress and achieved several key milestones in genomics research including genome sequence assemblies of wild diploid progenitors, wild tetraploid and both the subspecies of cultivated tetraploids, resequencing of diverse germplasm lines, genome-wide transcriptome atlas and cost-effective high and low-density genotyping assays. These genomic resources have enabled high-resolution trait mapping by using germplasm diversity panels and multi-parent genetic populations leading to precise gene discovery and diagnostic marker development. Furthermore, development and deployment of diagnostic markers have facilitated screening early generation populations as well as marker-assisted backcrossing breeding leading to development and commercialization of some molecular breeding products in groundnut. Several new genomics applications/technologies such as genomic selection, speed breeding, mid-density genotyping assay and genome editing are in pipeline. The integration of these new technologies hold great promise for developing climate-smart, high yielding and more nutritious groundnut varieties in the post-genome era.OBJECTIVE To evaluate the efficacy of a new technique of percutaneous vertebral augmentation (PVA) drill rotation-cement injected under vacuum aspiration (DR-CIVAS) for vertebral compression fractures (OVCFs) with intravertebral vacuum cleft (IVC) sign. MATERIALS AND METHODS A retrospective study was conducted in 46 consecutive patients with OVCFs and IVC signs, who underwent PVA using DR-CIVAS (n = 22, DR-CIVAS group) or traditional technique without DR-CIVAS (n = 24, control group). The pre- and postoperative vertebral height and wedge angle change and visual analog scale (VAS), the volume of cement injected, incidences of cement leakage, and subsequent new vertebral compression fractures were evaluated between the two groups. RESULTS No significant difference was found in cement leakage incidences, pre- and postoperative VAS scores, vertebral height, and wedge angle change between the two groups. The mean cement volume was significantly higher (P  less then  0.001) in DR-CIVAS group (4.87 mL) than in the control group (3.58 mL). Of the 22 patients in DR-CIVAS group, the subsequent fractures occurred in 2 cases (9.1%) located in the nonadjacent levels. In the control group, the subsequent fractures occurred in 6 cases (25.0%) located in the adjacent level (n = 1) and the augmented levels (n = 5). Although DR-CIVAS group did not demonstrate a statistical reduction of the incidence of subsequent fractures (P = 0.25), the subgroup analysis revealed that subsequent fractures frequently involved the augmented level in the control group (P = 0.04). CONCLUSIONS PVA with DR-CIVAS technique is effective for OVCFs with IVC sign, with lower incidences of subsequent new vertebral compression fractures in the augmented vertebra.Greulich and Pyle (GP) is one of the most common methods to determine bone age from hand radiographs. In recent years, new methods were developed to increase the efficiency in bone age analysis like the shorthand bone age (SBA) and automated artificial intelligence algorithms. OBJECTIVE The aim of this study is to evaluate the accuracy and reliability of these two methods and examine if the reduction in analysis time compromises their efficacy. METHODS Two hundred thirteen males and 213 females had their bone age determined by two separate raters using the SBA and GP methods. Three weeks later, the two raters repeated the analysis of the radiographs. The raters timed themselves using an online stopwatch. De-identified radiographs were securely uploaded to an automated algorithm developed by a group of radiologists in Toronto. The gold standard was determined to be the radiology report attached to each radiograph, written by experienced radiologists using GP. RESULTS Intraclass correlation between each method and the gold standard fell within the range of 0.8-0.9, highlighting significant agreement. Most of the comparisons showed a statistically significant difference between the new methods and the gold standard; however, it may not be clinically significant as it ranges between 0.25 and 0.5 years. A bone age is considered clinically abnormal if it falls outside 2 standard deviations of the chronological age; standard deviations are calculated and provided in GP atlas. CONCLUSION The shorthand bone age method and the automated algorithm produced values that are in agreement with the gold standard while reducing analysis time.Electroencephalographic (EEG) research indicates changes in adults’ low frequency bands of frontoparietal brain areas executing different balance tasks with increasing postural demands. However, this issue is unsolved for adolescents when performing the same balance task with increasing difficulty. Therefore, we examined the effects of a progressively increasing balance task difficulty on balance performance and brain activity in adolescents. Thirteen healthy adolescents aged 16-17 year performed tests in bipedal upright stance on a balance board with six progressively increasing levels of task difficulty. Postural sway and cortical activity were recorded simultaneously using a pressure sensitive measuring system and EEG. The power spectrum was analyzed for theta (4-7 Hz) and alpha-2 (10-12 Hz) frequency bands in pre-defined frontal, central, and parietal clusters of electrocortical sources. Repeated measures analysis of variance (rmANOVA) showed a significant main effect of task difficulty for postural sway oparietal brain areas in the regulation of postural control. In addition, we detected that activity of selected brain areas (e.g., bilateral central) changed with increasing postural demands.Surface exposed phosphatidylserine (PS) of cancer aids it to evade immune surveillance and thereby results in tumor progression. Earlier, we reported that PS targeting cationic liposomes, phosphatidylcholine-stearylamine (PC-SA), alone and in combination with doxorubicin can result in complete remission of B16F10 melanoma in C57BL/6 mice without signs of toxicity. Inducing an immunogenic response is highly crucial for any cancer therapy as it is essential in improving the tumor microenvironment for any drug to act. Herein, we demonstrate that PC-SA, besides having tumor reducing ability, elicits a strong immune response. The combination therapy (PC-SA-DOX) is superior to free DOX in enhancing the anti-tumor immune effect on CD4-positive and CD8-positive T cells for IFN-γ, IL-2 and TNF-α production in sera and splenic culture supernatants of B16F10 tumor-induced mice. An upregulation of IL-12 and NO production is evidenced in spleen cultures of these mice, thereby showing a promising role of both Th1 type and innate immune response for host anti-tumor activity. Complete elimination of cancer is sometimes accomplished by surgery, but its effectiveness is often limited due to the propensity of cancers to spread to distant organs by metastasis. In our present study, we show that in PC-SA-DOX treated mice, the elevated Th1 cytokine levels create an immuno-protective environment which thereby facilitates in curing lung metastasis. Our results, therefore, warrant the need of effective immune stimulation by anticancer formulations for inhibition of solid tumors and metastasis, demonstrated by the liposomal DOX formulation.This study shows that melanoma-associated fibroblasts (MAFs) suppress cytotoxic T lymphocyte (CTL) activity and reveals a pivotal role played by arginase in this phenomenon. MAFs and normal dermal fibroblasts (DFs) were isolated from surgically resected melanomas and identified as Melan-A-/gp100-/FAP+ cells. CTLs of healthy blood donors were activated in the presence of MAF- and DF-conditioned media (CM). Markers of successful CTL activation, cytotoxic degranulation, killing activity and immune checkpoint regulation were evaluated by flow cytometry, ELISPOT, and redirected killing assays. Soluble mediators responsible for MAF-mediated effects were identified by ELISA, flow cytometry, inhibitor assays, and knock-in experiments. In the presence of MAF-CM, activated/non-naïve CTLs displayed dysregulated ERK1/2 and NF-κB signaling, impeded CD69 and granzyme B production, impaired killing activity, and upregulated expression of the negative immune checkpoint receptors TIGIT and BTLA. Compared to DFs, MAFs displayed increased amounts of VISTA and HVEM, a known ligand of BTLA on T cells, increased L-arginase activity and CXCL12 release. Transgenic arginase over-expression further increased, while selective arginase inhibition neutralized MAF-induced TIGIT and BTLA expression on CTLs. Our data indicate that MAF interfere with intracellular CTL signaling via soluble mediators leading to CTL anergy and modify immune checkpoint receptor availability via L-arginine depletion.

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