Echocardiographic detection of left atrium and left ventricle tumoral invasion via the left upper pulmonary vein,leading to the diagnosis of lung cancer

Left atrial (LA) invasion by lung cancer via hematogenous pathways is relatively uncommon. Herein we report the case of a 68-year-old male without any medical history, in whom lung cancer was diagnosed by transesophageal echocardiographic detection of the LA and left ventricle tumoral invasion via the left upper pulmonary vein. The primary source of tumor was found out by computed tomography.     

Primary Ovarian Malignant Melanoma Arising in Teratomatous Component of Mixed- Germ Cell Tumor in a Child: Case report

Primary ovarian malignant melanoma arising in teratomatous component of germ cell tumors is seen extremely rare with most reports being only of single cases and small series in reproductive aged woman and mostly from cystic teratoma, whereas information on pediatric presentation is sparse. This case is reported for being extremely rare tumor.     

Factors Affecting the Intention to Quit among Women Smokers in Turkey

Objectives: Tobacco use is an important public health problem that affects adversely the quality of life. A person’s attitude toward quitting tobacco use can be reflected by the desire or intention to quit smoking. The aim of this study was to determine risk factors affecting women’s intention to quit tobacco in Turkey. Methods: In this study, the data obtained from the Global Adult Tobacco Survey (GATS) were used. The GATS is a standard method used in countries to monitor and evaluate the frequency of tobacco use in adults and tobacco control practices. The data used in the study was obtained from the GATS carried out in Turkey in 2008 and 2012. The data related to 1248 women smoking tobacco were used in the analysis. The relationship between women’s intention to quit tobacco use and socio-demographic and economic variables was examined. Results: Men were excluded from the analysis because the focus of the study was women. It was determined that 732 of 1248 women using tobacco intend to quit smoking tobacco. 40.4% of women smoking tobacco are primary school graduates. Women, who were aware of anti-smoking messages and exposed to stimulants that promote smoking, were 36.4% and 27% more likely to intend to stop tobacco use after the next month, respectively. It was observed that women living in a house, where smoking is allowed, are less likely to quit smoking than others (ME = -0.522). This shows the importance of domestic restrictions. Conclusion: Intending to quit is an important preliminary step to quit. Understanding the factors associated with the intention to quit smoking can help tobacco users to stop using it and shape effective policies to increase the quit rates.     

Scar evaluation in subperiosteal temporal pocket versus the one-layer flap technique in cochlear implantation using the Patient and Observer Scar Assessment Scale

European Archives of Oto-Rhino-Laryngology - To compare the local and intracranial complications, migration of the IRS, surgical duration, and quality of life with the subperiosteal pocket...     

Structure and dynamics of SARS-CoV-2 proofreading exoribonuclease ExoN

High-fidelity replication of the large RNA genome of coronaviruses (CoVs) is mediated by a 3′-to-5′ exoribonuclease (ExoN) in nonstructural protein 14 (nsp14), which excises nucleotides including antiviral drugs misincorporated by the low-fidelity viral RNA-dependent RNA polymerase (RdRp) and has also been implicated in viral RNA recombination and resistance to innate immunity. Here, we determined a 1.6-Å resolution crystal structure of severe acute respiratory syndrome CoV 2 (SARS-CoV-2) ExoN in complex with its essential cofactor, nsp10. The structure shows a highly basic and concave surface flanking the active site, comprising several Lys residues of nsp14 and the N-terminal amino group of nsp10. Modeling suggests that this basic patch binds to the template strand of double-stranded RNA substrates to position the 3′ end of the nascent strand in the ExoN active site, which is corroborated by mutational and computational analyses. We also show that the ExoN activity can rescue a stalled RNA primer poisoned with sofosbuvir and allow RdRp to continue its extension in the presence of the chain-terminating drug, biochemically recapitulating proofreading in SARS-CoV-2 replication. Molecular dynamics simulations further show remarkable flexibility of multidomain nsp14 and suggest that nsp10 stabilizes ExoN for substrate RNA binding to support its exonuclease activity. Our high-resolution structure of the SARS-CoV-2 ExoN–nsp10 complex serves as a platform for future development of anticoronaviral drugs or strategies to attenuate the viral virulence.

The 29.9-kb single-stranded RNA genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the global COVID-19 pandemic, is replicated and transcribed by the viral RNA-dependent RNA polymerase (RdRp, nsp12) (1–3). Unlike the high-fidelity cellular replicative DNA polymerases, viral RdRp enzymes, including the CoV RdRp, do not contain a proofreading exonuclease domain to ensure high fidelity. The resulting higher mutation rate (10⁻⁴ to 10⁻⁶ substitutions per nucleotide per round of replication) is generally thought to promote rapid viral adaptation in response to selective pressure (4–6). However, the lack of proofreading activity in RdRp poses a particular challenge for the replication of CoVs, which feature the largest known RNA virus genomes (27 to 32 kb, up to twice the length as the next-largest nonsegmented RNA viral genomes) (7, 8). It has been reported that SARS-CoV nsp12 is the fastest viral RdRp known but with an error rate more than one order of magnitude higher than the generally admitted error rate of viral RdRps (9), clearly necessitating a unique proofreading mechanism.To mitigate the low fidelity of RdRp, all coronaviruses encode a 3′-to-5′ exoribonuclease (ExoN) in multifunctional nsp14 (10–12), which forms a complex with nsp10 critical for the ExoN activity, and additionally contains a C-terminal guanine N7 methyl transferase (N7-MTase) domain. Mutations of SARS-CoV-2 nsp14 exhibit strong association with increased genome-wide mutation load (13, 14), and genetic inactivation of ExoN in engineered SARS-CoV and murine hepatitis virus (MHV) leads to 15- to 20-fold increases in mutation rates (7, 15, 16). Furthermore, in a mouse model, SARS-CoV with inactivated ExoN shows a mutator phenotype with decreased fitness and lower virulence over serial passage, suggesting a potential strategy for generating a live, impaired-fidelity coronavirus vaccine (17). Alternatively, recent studies show that ExoN inactivation abrogates replication of SARS-CoV-2 and Middle East Respiratory Syndrome CoV (18), hinting at additional functions for ExoN in viral replication. Indeed, ExoN activity has been reported to mediate the extensive viral RNA recombination required for subgenomic messenger RNA (mRNA) synthesis during normal replication of CoVs, including SARS-CoV-2 (19), and it was shown to be required for resistance to the antiviral innate immune response for MHV (20). ExoN inactivation also significantly increases the sensitivity of CoVs to nucleoside analogs that target RdRp, which is consistent with the biochemical activity of ExoN to excise mutagenic or chain-terminating nucleotides misincorporated by RdRp (21–23). These observations combine to suggest that chemical inhibition of ExoN could be an effective antiviral strategy against CoVs. In this study, we determined high-resolution crystal structures of the SARS-CoV-2 ExoN–nsp10 complex and studied its biochemical activities. Furthermore, we used molecular dynamics (MD) simulations to better understand the dynamics of nsp14, nsp10, and their interaction with RNA.     

Comparison of Adhesive Properties of Five Different Prosthetic Materials Used in Hernioplasty

This experimental study was designed to assess and to compare intra-abdominal adhesions following the use of five commercially available prosthetic mesh grafts in the repair if abdominal wall defects. Sixty Wistar albino rats were randomly divided into six groups (n = 10). A 2 × 1 cm defect at abdominal wall was created and defects were closed either primarily or with one of the following prosthetic mesh grafts: monofilament polypropylene, polytetrafluoroethylene, sodium hyaluronate/carboxymethylcellulose-coated polypropylene, polypropylene/polyglactin 910 composite, or resorbable hydrophilic collagen-coated multifiber polyester. The severity of adhesions was graded, tensile strengths of adhesions were measured, and histopathological grades of inflammation and fibrosis were evaluated. Polypropylene mesh resulted in more adhesion formation in comparison to primary repair and other grafts used in this study, except polypropylene/polyglactin 910 composite mesh. In addition, the highest tensile strength of omental adhesions was detected in the polypropylene group (χ² = 26.249; p =. 0001). Polyester composite mesh caused the least adhesion formation among the groups. Sodium hyaluronate/carboxymethylcellulose-coated polypropylene and polyester composite meshes revealed the highest fibrosis scores (χ² = 50.776; p =. 0001). The highest inflammatory activity was detected in the polytetrafluoroethylene mesh group (χ² = 16.564; p =. 005). Thus, sodium hyaluronate/carboxymethylcellulose-coated polypropylene and polytetrafluoroethylene meshes following polyester composite mesh were the minimal adhesion-forming grafts in this study. Disadvantages of the polytetrafluoroethylene mesh were lower fibrotic activity and higher inflammatory reaction to the graft.