Spontaneous Hemorrhagic Pericardial Effusion as a Consequence of Apixaban Utilization for New-Onset Atrial Fibrillation.

Although anticoagulation stands as a standardized therapeutic approach for mitigating thrombotic risks in atrial fibrillation, the potential for bleeding associated with direct oral anticoagulants (DOACs) is consistently weighed in the risk/benefit analysis prior to initiating therapy for non-valvular atrial fibrillation. While the typical bleeding risks from DOACs predominantly affect the gastrointestinal system, occurrences of spontaneous hemorrhagic pericardial effusions are rare. This case presentation illustrates a patient developing spontaneous hemorrhagic pericardial effusion four days after commencing apixaban therapy and subsequent management.

Anthropogenic land use and urbanization alter the dynamics and increase the export of dissolved carbon in an urbanized river system.

Greenhouse gas emissions from urban rivers play a crucial role in global carbon (C) cycling, this is tightly linked to dissolved C in rivers but research gaps remain. The effects of urbanization and anthropogenic land-use change on riverine dissolved carbon dynamics were investigated in a temperate river, the River Kelvin in UK. The river was constantly a source of methane (CH4) and carbon dioxide (CO2) to the atmosphere (excess concentration of CH4 ranged from 13 to 4441 nM, and excess concentration of CO2 ranged from 2.6 to 230.6 µM), and dissolved C concentrations show significant spatiotemporal variations (p < 0.05), reflecting a variety of proximal sources and controls. For example, the concentration variation of dissolved CH4 and dissolved CO2 were heavily controlled by the proximity of coal mine infrastructure in the tributary near the river head (~ 2 km) but were more likely controlled by adjacent landfills in the midstream section of the rivers main channel. Concentration and isotopic evidence revealed an important anthropogenic control on the riverine export of CO2 and dissolved organic carbon (DOC). However, dissolved inorganic carbon (DIC) input via groundwater at the catchment scale primarily controlled the dynamics of riverine DIC. Furthermore, the positive relationship between the isotopic composition of DIC and CO2 (r = 0.79, p < 0.01) indicates the DIC pool was at times also significantly influenced by soil respiratory CO2. Both DIC and DOC showed a weak but significant correlation with the proportion of urban/suburban land use, suggesting increased dissolved C export resulting from urbanization. This research elucidates a series of potentially key effects anthropogenic activities and land-use practices can have on riverine C dynamics and highlights the need for future consideration of the direct effects urbanization has on riverine C dynamics.

Drug-Coated Balloon Versus Plain Balloon Angioplasty for Hemodialysis Dysfunction: A Meta-Analysis of Randomized Controlled Trials.

Background Both drug-coated balloon (DCB) angioplasty and conventional plain balloon angioplasty (PBA) can be implemented to treat hemodialysis dysfunction. The present study aims to compare the safety and efficacy of these 2 approaches by conducting a meta-analysis of available randomized controlled trials. Methods and Results PubMed, Cochrane Library, and Embase databases were queried from establishment to January 2021. A total of 18 randomized controlled trials including 877 and 875 patients in the DCB and PBA groups, respectively, were included in the present meta-analysis. Target lesion primary patency, circuit patency, target lesion revascularization, and mortality were pooled. Odds ratios (ORs) were reported with 95% CIs. Publication bias was analyzed with funnel plot and Egger test. Target lesion primary patency was higher among patients who underwent DCB (OR, 2.93 [95% CI, 2.13-4.03], P<0.001 at 6 months; OR, 2.47 [95% CI, 1.53-3.99], P<0.001 at 1 year). Also, the DCB group had a higher dialysis circuit patency at 6 months (OR, 2.42; 95% CI, 1.56-3.77 [P<0.001]) and 1 year (OR, 1.91; 95% CI, 1.22-3.00 [P=0.005]). Compared with the PBA group, the DCB group had lower odds of target lesion revascularization during follow-up (OR, 0.43 [95% CI, 0.23-0.82], P=0.001 at 6 months; OR, 0.74 [95% CI, 0.32-1.73], P=0.490 at 1 year). The OR of mortality was comparable between 2 groups at 6 months (OR, 1.18; 95% CI, 0.42-3.33 [P=0.760]) and 1 year (OR, 0.93; 95% CI, 0.58-1.48 [P=0.750]). Conclusions Based on evidence from 18 randomized controlled trials, DCB angioplasty is superior to PBA in maintaining target lesion primary patency and circuit patency among patients with dialysis circuit stenosis. DCB angioplasty also reduces target lesion revascularization with a similar risk of mortality compared with PBA.

Blood plasma levels of heavy metals and trace elements in white sharks (Carcharodon carcharias) and potential health consequences.

Heavy metals may adversely affect health in marine organisms. As top predators, sharks may be especially vulnerable to exposure over long lifespans. Here we evaluate plasma levels of 14 heavy metals and 12 trace elements in white sharks, Carcharodon carcharias, in South Africa to determine whether they are related to sex, body size, and/or body condition and other health parameters. High levels of mercury and arsenic were found in shark blood at levels considered toxic in other vertebrates. Heavy metal concentrations were not related to body size or sex. Metal concentrations were not related to body condition with exception of copper, which was positively correlated. Protective effects of elements such as selenium, zinc, and iron were not detected. No negative effects on health parameters, such as total leukocytes or granulocyte to lymphocyte ratios were observed. Results suggest that sharks may have protective mechanisms that mitigate harmful effects of heavy metal exposure, providing new opportunities for future studies.

MicroScale Thermophoresis: A Rapid and Precise Method to Quantify Protein-Nucleic Acid Interactions in Solution.

Interactions between nucleic acids and proteins are driving gene expression programs and regulating the development of organisms. The binding affinities of transcription factors to their target sites are essential parameters to reveal their binding site occupancy and function in vivo. Microscale Thermophoresis (MST) is a rapid and precise method allowing for quantitative analysis of molecular interactions in solution on a microliter scale. The technique is based on the movement of molecules in temperature gradients, which is referred to as thermophoresis, and depends on molecule size, charge, and hydration shell. Since at least one of these parameters is typically affected upon binding of a ligand, the method can be used to analyze any kind of biomolecular interaction. This section provides a detailed protocol describing the analysis of DNA-protein interactions, using the transcription factor TTF-I as a model protein that recognizes a 10 bp long sequence motif.

Rotation of Guanine Amino Groups in G-Quadruplexes: A Probe for Local Structure and Ligand Binding.

Nucleic acids are dynamic molecules whose functions may depend on their conformational fluctuations and local motions. In particular, amino groups are dynamic components of nucleic acids that participate in the formation of various secondary structures such as G-quadruplexes. Here, we present a cost-efficient NMR method to quantify the rotational dynamics of guanine amino groups in G-quadruplex nucleic acids. An isolated spectrum of amino protons from a specific tetrad-bound guanine can be extracted from the nuclear Overhauser effect spectroscopy spectrum based on the close proximity between the intra-residue imino and amino protons. We apply the method in different structural contexts of G-quadruplexes and their complexes. Our results highlight the role of stacking and hydrogen-bond interactions in restraining amino-group rotation. The measurement of the rotation rate of individual amino groups could give insight into the dynamic processes occurring at specific locations within G-quadruplex nucleic acids, providing valuable probes for local structure, dynamics, and ligand binding.

Non-Canonical G-quadruplexes cause the hCEB1 minisatellite instability in Saccharomyces cerevisiae.

G-quadruplexes (G4) are polymorphic four-stranded structures formed by certain G-rich nucleic acids in vitro, but the sequence and structural features dictating their formation and function in vivo remains uncertain. Here we report a structure-function analysis of the complex hCEB1 G4-forming sequence. We isolated four G4 conformations in vitro, all of which bear unusual structural features: Form 1 bears a V-shaped loop and a snapback guanine; Form 2 contains a terminal G-triad; Form 3 bears a zero-nucleotide loop; and Form 4 is a zero-nucleotide loop monomer or an interlocked dimer. In vivo, Form 1 and Form 2 differently account for 2/3rd of the genomic instability of hCEB1 in two G4-stabilizing conditions. Form 3 and an unidentified form contribute to the remaining instability, while Form 4 has no detectable effect. This work underscores the structural polymorphisms originated from a single highly G-rich sequence and demonstrates the existence of non-canonical G4s in cells, thus broadening the definition of G4-forming sequences.

Influences on students' career decisions concerning general practice: a focus group study.

BACKGROUND: Despite concerns about recruitment to UK general practice, there has been no concerted educational intervention to address them. AIM: To better understand how medical students' perceptions of their experiences of their undergraduate curriculum may affect choosing general practice as a career. DESIGN AND SETTING: Qualitative study comprising focus groups of a total of 58 students from a range of medical schools across the UK. METHOD: A range of UK medical schools students were invited by email to participate in focus groups and return a questionnaire detailing their current career choice to facilitate sampling students with varied career preferences. Students late in their studies were sampled as they were likely to be considering future careers. Focus group discussions were audiotaped, transcribed, and anonymised for both school and participant, then thematically analysed. Perceived differences in medical school culture, curriculum philosophy, design, and intent were explored. RESULTS: Six focus groups (58 students) were convened. Some student participants' career aspirations were strongly shaped by family and home, but clinical placements remained important in confirming or refuting these choices. High-quality general practice attachments are a powerful attractor to general practice and, when they reflect authentic clinical practice, promote general practice careers. GP tutors can be powerful, positive role models. Students' comments revealed conflicting understandings about general practice. CONCLUSION: Attracting rather than coercing students to general practice is likely to be more effective at changing their career choices. Early, high-quality, ongoing and, authentic clinical exposure promotes general practice and combats negative stereotyping. It is recommended that increasing opportunities to help students understand what it means to be a 'good GP' and how this can be achieved are created.

Short loop length and high thermal stability determine genomic instability induced by G-quadruplex-forming minisatellites.

G-quadruplexes (G4) are polymorphic four-stranded structures formed by certain G-rich nucleic acids, with various biological roles. However, structural features dictating their formation and/or function in vivo are unknown. In S. cerevisiae, the pathological persistency of G4 within the CEB1 minisatellite induces its rearrangement during leading-strand replication. We now show that several other G4-forming sequences remain stable. Extensive mutagenesis of the CEB25 minisatellite motif reveals that only variants with very short (≤ 4 nt) G4 loops preferentially containing pyrimidine bases trigger genomic instability. Parallel biophysical analyses demonstrate that shortening loop length does not change the monomorphic G4 structure of CEB25 variants but drastically increases its thermal stability, in correlation with the in vivo instability. Finally, bioinformatics analyses reveal that the threat for genomic stability posed by G4 bearing short pyrimidine loops is conserved in C. elegans and humans. This work provides a framework explanation for the heterogeneous instability behavior of G4-forming sequences in vivo, highlights the importance of structure thermal stability, and questions the prevailing assumption that G4 structures with short or longer loops are as likely to form in vivo.

Structure and conformational dynamics of a stacked dimeric G-quadruplex formed by the human CEB1 minisatellite.

CEB1 is a highly polymorphic human minisatellite. In yeast, the size variation of CEB1 tandem arrays has been associated with the capacity of the motif to form G-quadruplexes. Here we report on the NMR solution structure of a G-quadruplex formed by the CEB1 DNA G-rich fragment d(AGGGGGGAGGGAGGGTGG), harboring several G-tracts including one with six continuous guanines. This sequence forms a dimeric G-quadruplex involving the stacking of two subunits, each being a unique snapback parallel-stranded scaffold with three G-tetrad layers, three double-chain-reversal loops, and a V-shaped loop. The two subunits are stacked at their 5'-end tetrads, and multiple stacking rotamers may be present due to a high symmetry at the stacking interface. There is a conformational exchange in the millisecond time scale involving a swapping motion between two bases of the six-guanine tract. Our results not only add to the understanding of how the G-quadruplex formation in human minisatellite leads to genetic instability but also address the fundamental questions regarding stacking of G-quadruplexes and how a long continuous G-tract participates in the structure and conformational dynamics of G-quadruplexes.

NMR spectroscopy of G-quadruplexes.

G-rich DNA and RNA sequences can form four-stranded structures called G-quadruplexes. Such structures have gained significant interest in the past decade with increasing evidence of their biological role. G-quadruplex structures can be polymorphic and dynamic. NMR spectroscopy has played an important role in G-quadruplex research. Here we review on the application of NMR techniques to study structure, dynamics and interaction of G-quadruplexes.

Formation of pearl-necklace monomorphic G-quadruplexes in the human CEB25 minisatellite.

CEB25 is a human minisatellite locus, composed of slightly polymorphic 52-nucleotide (nt) tandem repeats. Genetically, most if not all individuals of the human population are heterozygous, carrying alleles ranging from 0.5 to 20 kb, maintained by mendelian inheritance but also subject to germline instability. To provide insights on the biological role of CEB25, we interrogated its structural features. We report the NMR structure of the G-quadruplex formed by the conserved 26-nt G-rich fragment of the CEB25 motif. In K(+) solution, this sequence forms a propeller-type parallel-stranded G-quadruplex involving a 9-nt central double-chain-reversal loop. This long loop is anchored to the 5'-end of the sequence by an A·T Watson-Crick base pair and a potential G·A noncanonical base pair. These base pairs contribute to the stability of the overall G-quadruplexstructure, as measured by an increase of about 17 kcal/mol in enthalpy or 6 °C in melting temperature. Further, we demonstrate that such a monomorphic structure is formed within longer sequence contexts folding into a pearl-necklace structure.

An unusual case of ectopic or "parasitic" leiomyoma excised by laparoscopic surgery.

A 47-year-old woman underwent a laparoscopic resection of a large ectopic or "parasitic" fibroid filling the pelvis and placed within the rectosigmoid mesentery. The tumor was excised completely without a need for hysterectomy. Immunohistochemical and ultrastructural studies confirmed a "parasitic" leiomyoma, excluding sarcoma or a gastrointestinal stromal tumor. Because of its bizarre location in relation to the large bowel, a combined general surgical and gynecological approach was used successfully. The pathology of this rare tumor is reviewed.