Global dynamic topography observations reveal limited influence of large-scale mantle flow

Convective circulation of the Earth’s mantle maintains some fraction of surface topography that varies with space and time. Most predictive models show that this dynamic topography has peak amplitudes of about ±2km, dominated by wavelengths of 10⁴km. Here, we test these models against our comprehensive observational database of 2,120 spot measurements of dynamic topography that were determined by analysing oceanic seismic surveys. These accurate measurements have typical peak amplitudes of ±1km and wavelengths of approximately 10³km, and are combined with limited continental constraints to generate a global spherical harmonic model whose robustness has been carefully tested and benchmarked. Our power spectral analysis reveals significant discrepancies between observed and predicted dynamic topography. At longer wavelengths (such as 10⁴km), observed dynamic topography has peak amplitudes of about ±500m. At shorter wavelengths (such as 10³km), significant dynamic topography is still observed. We show that these discrepancies can be explained if short-wavelength dynamic topography is generated by temperature-driven density anomalies within a sub-plate asthenospheric channel. Stratigraphic observations from adjacent continental margins show that these dynamic topographic signals evolve quickly with time. More rapid temporal and spatial changes in vertical displacement of the Earth’s surface have direct consequences for fields as diverse as mantle flow, oceanic circulation and long-term climate change

New Media and Crisis Management in Jordan: COVID 19 Perspective

The study aimed at identifying the relationship between the most effective digital media in managing the Corona crisis in Jordan; and the contribution of digital media in managing the (Covid 19) crisis. To achieve the aims of the study, the researcher adopted the quantitative survey method using an electronic questionnaire designed to collect data. It was distributed to an intentional sample of 50 employees (males and females) from the communication and media staff in the Jordanian government institutions. The study concluded that the most effective digital communication technologies in managing the Corona crisis were press conferences (media briefings), press coverage through digital platforms, electronic news, video reports and community initiatives through social media platforms. The results also showed that digital media contributed to managing the Corona crisis in Jordan by relying on effective and organized digital crisis communication, which helped to coordinate efforts with the relevant health and security authorities in the country about the disease developments and the decisions related, besides the immediate responses to inquiries and questions of reviewers and callers about preventive health procedures and measures of safety from the Corona virus. In light of these results, the study recommended that media briefings in crises through digital media should be adopted due to their effectiveness in managing health crises facing countries, as one of the most effective methods of digital communication technologies

The Effect of Misuse of Topical Corticosteroids on Skin

Objectives: To assess the frequency of misuse of TC on skin , commonly used steroids and the most common dermatological problems resulting from it, as well as, to analyze the motives for such practices with the aim to raise awareness about this problem in Mosul city. Methods: The study included 155 patients aged 0.8-49 years with dermatological disorders who attended Outpat­ient Department of Dermatology in Al-Salam Teaching Hospital in Mosul City . Inclusion criteria: those who had used TC without medical advice; continued use after short prescription regardless of the duration ;TC used incorrectly or used them for certain skin problems for which steroids are not indicated; Wrong indication (acne); undiagnosed dermatosis as well as a history of TC use continuously(for more than1 month) or intermittently (for more than 3 months) due to any purpose, and presented with ≥ 1 of the side-effects of these drugs as the chief complaint were criteria used to define unjustifiable/inappropriate use. Patients with natural rosacea; those denying any history of using TC or who not consenting to answering the questionnaire; pregnant women; patients who were using prescribed TC regardless of the duration or side effects such as asthma, rheumatoid arthritis; patients with comorbidities that resembled/could cause changes similar to TC side-effects (polycystic ovaries / Cushing's syndrome/thyroid disorders)were excluded from the study. A questionnaire was designated and skin was examined to study patients. Results: Of the 155 subjects misused TC most were females 98(63.23%)  and 57(36.77%) were males; of low social class 45(29%). The majority 123(85.2%) thought that corticosteroid use was safe and 56(36.1%) did not feel guilty for using such medications. Eighty fife(55 %)patients reported that physician and pharmacists advised them for the first time to use TC. Ninety eight (63.3%) patients obtained the drug from the pharmacies, 30(19.3%)from nurse staff and 27(17.4%) from cosmetic shop/Beautician. lightening of the skin (30.6%)  was the main indication for use TC. Potent and very potent preparations were the main TC used by patients.Almost all had some features of TC side effects. Conclusion: Inappropriate use of TC is a big problem in our country. Easy availability of very potent products without a prescription makes misuse very common which has a huge impact on derm­atological practice. It is responsible for a significant proportion of visits to dermatolo­gy clinics. It is a multiphase problem that needs the cooperation of different sectors in the community to overcome it. Education of the general public through special media programs and the introduction of a continuing medical education programs for medical and paramedical personnel as well as controlling the easy intake from pharmacies are probably the most important steps that could be taken to reduce this problem

Pseudoaneurysm of the left ventricle following apical approach TAVI

Symptomatic severe aortic stenosis carries a two year survival of only 50%. However many patients are unsuitable for conventional aortic valve replacement as they are considered too high risk due to significant co-morbidities. Transcatheter Aortic Valve Implantation (TAVI) offers a viable alternative for this high risk patient group, either by the femoral or apical route. This article reports a case of a pseudoaneurysm of the left ventricle following an apical approach TAVI in an elderly lady with severe aortic stenosis. To our knowledge pseduoaneuryms of the left ventricle have been reported infrequently in the literature and has yet to be established as a recognised complication of TAVI

Quantitative and qualitative differences in subcutaneous adipose tissue stores across lipodystrophy types shown by magnetic resonance imaging

BACKGROUND: Lipodystrophies are characterized by redistributed subcutaneous fat stores. We previously quantified subcutaneous fat by magnetic resonance imaging (MRI) in the legs of two patients with familial partial lipodystrophy subtypes 2 and 3 (FPLD2 and FPLD3, respectively). We now extend the MRI analysis across the whole body of patients with different forms of lipodystrophy. METHODS: We studied five subcutaneous fat stores (supraclavicular, abdominal, gluteal, thigh and calf) and the abdominal visceral fat stores in 10, 2, 1, 1 and 2 female subjects with, respectively, FPLD2, FPLD3, HIV-related partial lipodystrophy (HIVPL), acquired partial lipodystrophy (APL), congenital generalized lipodystrophy (CGL) and in six normal control subjects. RESULTS: Compared with normal controls, FPLD2 subjects had significantly increased supraclavicular fat, with decreased abdominal, gluteal, thigh and calf subcutaneous fat. FPLD3 subjects had increased supraclavicular and abdominal subcutaneous fat, with less severe reductions in gluteal, thigh and calf fat compared to FPLD2 subjects. The repartitioning of fat in the HIVPL subject closely resembled that of FPLD3 subjects. APL and CGL subjects had reduced upper body, gluteal and thigh subcutaneous fat; the APL subject had increased, while CGL subjects had decreased subcutaneous calf fat. Visceral fat was markedly increased in FPLD2 and APL subjects. CONCLUSION: Semi-automated MRI-based adipose tissue quantification indicates differences between various lipodystrophy types in these studied clinical cases and is a potentially useful tool for extended quantitative phenomic analysis of genetic metabolic disorders. Further studies with a larger sample size are essential for confirming these preliminary findings

High Cysteinyl Leukotriene Receptor 1 Expression Correlates with Poor Survival of Uveal Melanoma Patients and Cognate Antagonist Drugs Modulate the Growth, Cancer Secretome, and Metabolism of Uveal Melanoma Cells

Simple Summary This research investigates the disease relevance and therapeutic potential of cysteinyl leukotriene receptors in uveal melanoma (UM), a rare eye cancer that often spreads to the liver. Unfortunately, there are no therapies available to stop the spread of UM and patients are often faced with an extremely poor prognosis. We assess whether the cysteinyl leukotriene receptors (CysLT(1) and CysLT(2)) are relevant to the progression of UM. Using UM patient samples, we identified that increased levels of CysLT(1) in tumours is associated with reduced patient survival. Using UM cell lines and zebrafish models, we found that drugs targeting CysLT(1), but not CysLT(2), can alter hallmarks of cancer including cell growth, proliferation, and metabolism. This study is the first to examine the relationship of the CysLT receptors with clinical features of UM. Our data strengthen the importance of CysLT signalling in UM and suggest that antagonism of CysLT(1) may be of therapeutic interest in the disease. Metastatic uveal melanoma (UM) is a rare, but often lethal, form of ocular cancer arising from melanocytes within the uveal tract. UM has a high propensity to spread hematogenously to the liver, with up to 50% of patients developing liver metastases. Unfortunately, once liver metastasis occurs, patient prognosis is extremely poor with as few as 8% of patients surviving beyond two years. There are no standard-of-care therapies available for the treatment of metastatic UM, hence it is a clinical area of urgent unmet need. Here, the clinical relevance and therapeutic potential of cysteinyl leukotriene receptors (CysLT(1) and CysLT(2)) in UM was evaluated. High expression of CYSLTR1 or CYSLTR2 transcripts is significantly associated with poor disease-free survival and poor overall survival in UM patients. Digital pathology analysis identified that high expression of CysLT(1) in primary UM is associated with reduced disease-specific survival (p = 0.012; HR 2.76; 95% CI 1.21-6.3) and overall survival (p = 0.011; HR 1.46; 95% CI 0.67-3.17). High CysLT(1) expression shows a statistically significant (p = 0.041) correlation with ciliary body involvement, a poor prognostic indicator in UM. Small molecule drugs targeting CysLT(1) were vastly superior at exerting anti-cancer phenotypes in UM cell lines and zebrafish xenografts than drugs targeting CysLT(2). Quininib, a selective CysLT(1) antagonist(,) significantly inhibits survival (p < 0.0001), long-term proliferation (p < 0.0001), and oxidative phosphorylation (p < 0.001), but not glycolysis, in primary and metastatic UM cell lines. Quininib exerts opposing effects on the secretion of inflammatory markers in primary versus metastatic UM cell lines. Quininib significantly downregulated IL-2 and IL-6 in Mel285 cells (p < 0.05) but significantly upregulated IL-10, IL-1 beta, IL-2 (p < 0.0001), IL-13, IL-8 (p < 0.001), IL-12p70 and IL-6 (p < 0.05) in OMM2.5 cells. Finally, quininib significantly inhibits tumour growth in orthotopic zebrafish xenograft models of UM. These preclinical data suggest that antagonism of CysLT(1), but not CysLT(2), may be of therapeutic interest in the treatment of UM

Chromatin and epigenetics: current biophysical views

Recent advances in high-throughput sequencing experiments and their theoretical descriptions have determined fast dynamics of the "chromatin and epigenetics" field, with new concepts appearing at high rate. This field includes but is not limited to the study of DNA-protein-RNA interactions, chromatin packing properties at different scales, regulation of gene expression and protein trafficking in the cell nucleus, binding site search in the crowded chromatin environment and modulation of physical interactions by covalent chemical modifications of the binding partners. The current special issue does not pretend for the full coverage of the field, but it rather aims to capture its development and provide a snapshot of the most recent concepts and approaches. Eighteen open-access articles comprising this issue provide a delicate balance between current theoretical and experimental biophysical approaches to uncover chromatin structure and understand epigenetic regulation, allowing free flow of new ideas and preliminary results

A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3×10-6) had not been highlighted in previous studies. While rs56137030was correlated at r2>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations