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Skipper Mckinney opublikował 5 miesięcy, 2 tygodnie temu
This review summarizes these unique and exciting discoveries of the regulatory factors controlling the globin switch. New insights and novel leads for therapeutic strategies based on the pharmacological induction of HbF are discussed. This represents a major breakthrough for rational drug design in the treatment of β-Thal and SCD.PURPOSE OF REVIEW The current review focuses on recent insights into the development of small molecule therapeutics to treat the β-globinopathies. RECENT FINDINGS Recent studies of fetal γ-globin gene regulation reveal multiple insights into how γ-globin gene reactivation may lead to novel treatment for β-globinopathies. SUMMARY We summarize current information regarding the binding of transcription factors that appear to be impeded or augmented by different hereditary persistence of fetal hemoglobin (HPFH) mutations. As transcription factors have historically proven to be difficult to target for therapeutic purposes, we next address the contributions of protein complexes associated with these HPFH mutation-affected transcription factors with the aim of defining proteins that might provide additional targets for chemical molecules to inactivate the corepressors. Among the enzymes associated with the transcription factor complexes, a group of corepressors with currently available inhibitors were initially thought to be good candidates for potential therapeutic purposes. We discuss possibilities for pharmacological inhibition of these corepressor enzymes that might significantly reactivate fetal γ-globin gene expression. Finally, we summarize the current clinical trial data regarding the inhibition of select corepressor proteins for the treatment of sickle cell disease and β-thalassemia.PURPOSE OF REVIEW The aim of this study was to identify similarities, differences and lessons to be shared from recent progress in HIV and hepatitis B virus (HBV) immunotherapeutic approaches. RECENT FINDINGS Immune dysregulation is a hallmark of both HIV and HBV infection, which have shared routes of transmission, with approximately 10% of HIV-positive patients worldwide being coinfected with HBV. Immune modulation therapies to orchestrate effective innate and adaptive immune responses are currently being sought as potential strategies towards a functional cure in both HIV and HBV infection. These are based on activating immunological mechanisms that would allow durable control by triggering innate immunity, reviving exhausted endogenous responses and/or generating new immune responses. Recent technological advances and increased appreciation of humoral responses in the control of HIV have generated renewed enthusiasm in the cure field. SUMMARY For both HIV and HBV infection, a primary consideration with immunomodulatory therapies continues to be a balance between generating highly effective immune responses and mitigating any significant toxicity. A large arsenal of new approaches and ongoing research offer the opportunity to define the pathways that underpin chronic infection and move closer to a functional cure.BACKGROUND The long-term results of soft tissue rebalancing procedures of the shoulder in obstetric brachial plexus palsy have been scarcely reported. The effect of this procedure on the evolution of secondary bone changes has been a subject of controversy. METHODS Twenty-six children are included in this study. All initially had postganglionic C5-6 or C5-7 (Narakas types I and II) obstetric brachial plexus palsy, which spontaneously recovered. Children included are those who had persistent external rotation weakness with or without internal rotation contracture, nondysplastic glenohumeral joint, and functioning teres major. All had anterior shoulder release and teres major to infraspinatus transfer to correct internal rotation deformity and/or increase active shoulder external rotation. Patients were 18 males and 8 females. The right upper limb was affected in 16 patients, and the left in 10. Surgery was performed at an average age of 3.01 years (range, 1-10 years). Follow-up averaged 8.2 years (range, 5-16 otation. The difference in glenoid version and humeral head subluxation continued to be insignificant compared with the normal side.Glycogen-rich clear cell carcinoma (GRCC) is a very rare form of primary breast cancer ( less then 0.1% of all breast cancers). It is characterized by the presence of neoplastic cells with a glycogen-abundant clear cytoplasm (the Periodic Acid Schiff-positive, diastase-sensitive). The expression of steroid receptors (estrogen and progesterone receptors) has been variably reported (35% to 100% of the cases), whereas most studies reported low human epidermal growth factor receptor 2 positivity in GRCC. High androgen receptor positivity without androgen receptor splice variant-7 was reported in one recent study. Although sparse, the preliminary theranostic data on GRCC indicate the potential of targeted treatments in selected cases (antiandrogen, PIK3CA, and immune checkpoint inhibitors). Because of its rarity, the prognosis for GRCC patients remains controversial. Herein, we comprehensively appraise the epidemiological, morphologic, molecular, and clinical characteristics of this rare mammary malignancy.In this edition of the journal, there is an important nested case-control study from investigators at Kaiser Permanente, Northern California. Proton pump inhibitor exposure for 10 or more years was not associated with any increased risk of gastric cancer. Small observed increased risks of colorectal, hepatocellular, and pancreatic cancers with 10 or more years of exposure are likely to have been spurious. If proton pump inhibitors were to be impeached on the basis of gastrointestinal cancer risk, they are likely to be subsequently acquitted.OBJECTIVES Delayed postpolypectomy bleeding (DPPB) is a relatively common adverse event. Evidence is conflicting on the efficacy of prophylactic clipping to prevent DPPB, and real-world effectiveness data are lacking. We aimed to determine the effectiveness of prophylactic clipping in preventing DPPB in a large screening-related cohort. METHODS We manually reviewed records of patients who underwent polypectomy from 2008 to 2014 at a screening facility. Endoscopist-, patient- and polyp-related data were collected. The primary outcome was DPPB within 30 days. All unplanned healthcare visits were reviewed; DPPB cases were adjudicated by committee using a criterion-based lexicon. Multivariable logistic regression was performed, yielding adjusted odds ratios (AORs) for the association between clipping and DPPB. Secondary analyses were performed on procedures where one polyp was removed, in addition to propensity score-matched and subgroup analyses. RESULTS In total, 8,366 colonoscopies involving polypectomy were analyzed, yielding 95 DPPB events. Prophylactic clipping was not associated with reduced DPPB (AOR 1.27; 0.83-1.96). These findings were similar in the single-polyp cohort (n = 3,369, AOR 1.07; 0.50-2.31). In patients with one proximal polyp ≥20 mm removed, there was a nonsignificant AOR with clipping of 0.55 (0.10-2.66). Clipping was not associated with a protective benefit in the propensity score-matched or other subgroup analyses. DISCUSSION In this large cohort study, prophylactic clipping was not associated with lower DPPB rates. Endoscopists should not routinely use prophylactic clipping in most patients. Additional effectiveness and cost-effectiveness studies are required in patients with proximal lesions ≥20 mm, in whom there may be a role for prophylactic clipping.OBJECTIVE The objective of this study was to examine the correlation between Twitter mentions and the number of academic citations of radiation oncology articles. MATERIALS AND METHODS We reviewed all 178 clinical manuscripts of the 2 most important radiation oncology journals and „Brachytherapy,” and all clinical manuscripts relating to radiation oncology from the top 10 impact factor oncology journals, published between January and February 2018. We collected the record of citations utilizing Scopus and Google Scholar platforms and the number of times an article was tweeted about using the „Altmetric Bookmarklet.” χ test was used to compare distributions between groups and the Pearson coefficient was used for correlations between the Twitter metrics and academic citations. RESULTS Overall, 71% of all articles were tweeted about at least once. There was a significant correlation between the number of tweets and the number of citations in Google Scholar (r=0.55, P less then 0.001) and in Scopus (r=0.59, P less then 0.001). The 11% of articles with a prepublication Twitter „buzz” (defined as an article with ≥10 tweets before publication) had 3.6 times more citations in Scopus (mean 14.8 vs. 4.2, P less then 0.001) and 2.9 times more citations in Google Scholar (17.8 vs. 6.0, P less then 0.001) when compared with papers with no „buzz.” CONCLUSIONS Presence on Twitter was correlated with the number of academic citations of an article in radiation oncology. This suggests that Twitter is being utilized by the oncology community as a platform to discuss and disseminate high impact scientific articles. The correlation between Twitter and increasing the number of citations of an article through larger dissemination and exposure requires further studies.Micro four-point probes (M4PP) provide rapid and automated lithography-free transport properties of planar surfaces including two-dimensional materials. We perform sheet conductance wafer maps of graphene directly grown on a 100 mm diameter SiC wafer using a multiplexed seven-point probe with minor additional measurement time compared to a four-point probe. Comparing the results of three subprobes we find that compared to a single-probe result, our measurement yield increases from 72%-84% to 97%. The additional data allows for correlation analysis between adjacent subprobes, that must measure the same values in case the sample is uniform on the scale of the electrode pitch. We observe that the relative difference in measured sheet conductance between two adjacent subprobes increase in the transition between large and low conductance regions. We mapped sheet conductance of graphene as it changed over several weeks. Terahertz time-domain spectroscopy conductivity maps both before and after M4PP mapping showed no significant change due to M4PP measurement, with both methods showing the same qualitative changes over time.In this work, we reported the tailored design of highly efficient Fe3O4-Au magnetic nanocomposite (MNP) catalysts. Fe3O4 nanocrystals with three different morphologies have been developed with engineered amounts of urea, and the plausible mechanism has been proposed. Then by controlling the amount of Au seeds, Fe3O4-Au MNPs with different morphologies and tunable Au deposition have been realized. Characterizations including x-ray diffraction (XRD), transmission electron microscopy (TEM), Mössbauer spectra, and elemental mapping are implemented to unveil the structural and physical characteristics of the successfully developed Fe3O4-Au MNPs with different morphologies. The catalytic ability of Fe3O4-Au MNPs with different morphologies have been compared by applying them to degrading RhB and 4-NP, meanwhile the correlation between the amount of Au seeds and the turnover frequency as well as the catalytic ability of Fe3O4-Au MNPs is investigated systematically. We found that the flower-like Fe3O4-Au MNPs with 20 ml Au seeds added achieved the best degradation efficiency of 96.