An Analysis of Putative Roles for the CCR4-NOT Deadenylase-Complex Subunit Regena (NOT2) in microRNA-Mediated Gene Silencing in \u3cem\u3eDrosophila Melanogaster\u3c/em\u3e

microRNAs (miRNAs) are one class of small non-coding ribonucleic acid (RNA) molecules essential to development and homeostasis in plants and animals. miRNAs silence gene expression through complementary base pairing with target gene messenger RNAs and association with the miRNA-induced silencing complex (miRISC). The identification and characterization of cellular factors required for miRNA-mediated gene silencing is incomplete. A forward genetic screen was carried out in Drosophila melanogaster to generate flies defective for gene silencing. Silencing was assayed by expression of a Green Fluorescent Protein (GFP) reporter fused to the Brd gene 3’ UTR, which is regulated by miRNAs. Genetic analysis revealed that the CCR4-NOT deadenylase-complex subunit Regena (NOT2) is required for miRNA-mediated silencing of the reporter. In addition, perturbation of Regena function altered Drosophila eye development and resulting adult eye morphology. miRNAs are thought to silence target gene expression through a combination of translational repression and target mRNA degradation, though the detailed mechanism of this process is a matter of controversy. Novel genetic reagents to explore miRNA function in vivo have been generated and characterized. Ongoing efforts aim to explore whether Regena is required to silence other miRNA targets in vivo, and whether Regena is required for miRNA-mediated gene silencing at different stages of the Drosophila life cycle. Elucidation of the lesion in the Regena (NOT2) gene and the molecular nature of GFP reporter silencing will contribute to an understanding of the mechanism of miRNA-mediated gene silencing in vivo

Rain volume estimation over areas using satellite and radar data

The analysis of 18 convective clusters demonstrates that the extension of the Area-Time-Integral (ATI) technique to the use of satellite data is possible. The differences of the internal structures of the radar reflectivity features, and of the satellite features, give rise to differences in estimating rain volumes by delineating area; however, by focusing upon the area integrated over the lifetime of the storm, it is suggested that some of the errors produced by the differences in the cloud geometries as viewed by radar or satellite are minimized. The results are good and future developments should consider data from different climatic regions and should allow for implementation of the technique in a general circulation model

Predictors and outcomes of crossover to surgery from physical therapy for meniscal tear and osteoarthritis a randomized trial comparing physical therapy and surgery

BACKGROUND: Arthroscopic partial meniscectomy (APM) combined with physical therapy (PT) have yielded pain relief similar to that provided by PT alone in randomized trials of subjects with a degenerative meniscal tear. However, many patients randomized to PT received APM before assessment of the primary outcome. We sought to identify factors associated with crossing over to APM and to compare pain relief between patients who had crossed over to APM and those who had been randomized to APM. METHODS: We used data from the MeTeOR (Meniscal Tear in Osteoarthritis Research) Trial of APM with PT versus PT alone in subjects ≥45 years old who had mild-to-moderate osteoarthritis and a degenerative meniscal tear. We assessed independent predictors of crossover to APM among those randomized to PT. We also compared pain relief at 6 months among those randomized to PT who crossed over to APM, those who did not cross over, and those originally randomized to APM. RESULTS: One hundred and sixty-four subjects were randomized to and received APM and 177 were randomized to PT, of whom 48 (27%) crossed over to receive APM in the first 140 days after randomization. In multivariate analyses, factors associated with a higher likelihood of crossing over to APM among those who had originally been randomized to PT included a baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score of ≥40 (risk ratio [RR] = 1.99; 95% confidence interval [CI] = 1.00, 3.93) and symptom duration of <1 year (RR = 1.74; 95% CI = 0.98, 3.08). Eighty-one percent of subjects who crossed over to APM and 82% of those randomized to APM had an improvement of ≥10 points in their pain score at 6 months, as did 73% of those who were randomized to and received only PT. CONCLUSIONS: Subjects who crossed over to APM had presented with a shorter symptom duration and greater baseline pain than those who did not cross over from PT. Subjects who crossed over had rates of surgical success similar to those of the patients who had been randomized to surgery. Our findings also suggest that an initial course of rigorous PT prior to APM may not compromise surgical outcome. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence

Association between Psychotic Symptoms and Cortical Thickness Reduction across the Schizophrenia Spectrum

The current study provides a complete MRI analysis of thickness throughout the cerebral cortical mantle in patients with schizophrenia (SZ) and rigorously screened and matched unaffected relatives and controls and an assessment of its relation to psychopathology and subjective cognitive function. We analyzed 3D-anatomical magnetic resonance imaging data sets, obtained at 3 Tesla, from three different subject groups: 25 SZ patients, 29 first-degree relatives and 37 healthy control subjects. We computed whole-brain cortical thickness using the Freesurfer software and assessed group differences. We also acquired clinical and psychometric data. The results showed markedly reduced cortical thickness in SZ patients compared with controls, most notably in the frontal and temporal lobes, in the superior parietal lobe and several limbic areas, with intermediate levels of cortical thickness in relatives. In both patients and relatives, we found an association between subjective cognitive dysfunction and reduced thickness of frontal cortex, and predisposition towards hallucinations and reduced thickness of the superior temporal gyrus. Our findings suggest that changes in specific cortical areas may predispose to specific symptoms, as exemplified by the association between temporal cortex thinning and hallucinations

Herbal substance, acteoside, alleviates intestinal mucositis in mice

This study investigated the role of acteoside in the amelioration of mucositis. C57BL/6 mice were gavaged daily with acteoside 600 μg for 5 d prior to induction of mucositis and throughout the experimental period. Mucositis was induced by methotrexate (MTX; 12.5 mg/kg; s.c.). Mice were culled on d 5 and d 11 after MTX. The duodenum, jejunum, and ileum were collected for myeloperoxidase (MPO) activity, metallothionein (MT) levels, and histology. Acteoside reduced histological severity scores by 75, 78, and 88% in the duodenum, jejunum, and ileum, respectively, compared to MTX-controls on d 5. Acteoside reduced crypt depth by 49, 51, and 33% and increased villus height by 19, 38, and 10% in the duodenum, jejunum, and ileum, respectively, compared to MTX-controls on d 5. Acteoside decreased MT by 50% compared to MTX-control mice on d 5. Acteoside decreased MPO by 60% and 30% in the duodenum and jejunum, respectively, compared to MTX-controls on d 5. Acteoside alleviated MTX-induced small intestinal mucositis possibly by preventing inflammation.Daniel Reinke, Stamatiki Kritas, Panagiotis Polychronopoulos, Alexios L. Skaltsounis, Nektarios Aligiannis, and Cuong D. Tra

Management of Dyspnea in Advanced Cancer: ASCO Guideline.

PURPOSE To provide guidance on the clinical management of dyspnea in adult patients with advanced cancer. METHODS ASCO convened an Expert Panel to review the evidence and formulate recommendations. An Agency for Healthcare Research and Quality (AHRQ) systematic review provided the evidence base for nonpharmacologic and pharmacologic interventions to alleviate dyspnea. The review included randomized controlled trials (RCTs) and observational studies with a concurrent comparison group published through early May 2020. The ASCO Expert Panel also wished to address dyspnea assessment, management of underlying conditions, and palliative care referrals, and for these questions, an additional systematic review identified RCTs, systematic reviews, and guidelines published through July 2020. RESULTS The AHRQ systematic review included 48 RCTs and two retrospective cohort studies. Lung cancer and mesothelioma were the most commonly addressed types of cancer. Nonpharmacologic interventions such as fans provided some relief from breathlessness. Support for pharmacologic interventions was limited. A meta-analysis of specialty breathlessness services reported improvements in distress because of dyspnea. RECOMMENDATIONS A hierarchical approach to dyspnea management is recommended, beginning with dyspnea assessment, ascertainment and management of potentially reversible causes, and referral to an interdisciplinary palliative care team. Nonpharmacologic interventions that may be offered to relieve dyspnea include airflow interventions (eg, a fan directed at the cheek), standard supplemental oxygen for patients with hypoxemia, and other psychoeducational, self-management, or complementary approaches. For patients who derive inadequate relief from nonpharmacologic interventions, systemic opioids should be offered. Other pharmacologic interventions, such as corticosteroids and benzodiazepines, are also discussed