Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by mutations in the cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) and can be difficult to treat. The class Ic antiarrhythmic drug flecainide blocks RyR2 channels and prevents CPVT in mice and humans. It is not known whether other class I antiarrhythmic drugs also block RyR2 channels and to what extent RyR2 channel inhibition contributes to antiarrhythmic efficacy in CPVT. Methods and Results We first measured the effect of all class I antiarrhythmic drugs marketed in the United States (quinidine, procainamide, disopyramide, lidocaine, mexiletine, flecainide, and propafenone) on single RyR2 channels incorporated into lipid bilayers. Only flecainide and propafenone inhibited RyR2 channels, with the S-enantiomer of propafenone having a significantly lower potency than R-propafenone or flecainide. In Casq2−/− myocytes, the propafenone enantiomers and flecainide significantly reduced arrhythmogenic Ca2+ waves at clinically relevant concentrations, whereas Na+ channel inhibitors without RyR2 blocking properties did not. In Casq2−/− mice, 5 mg/kg R-propafenone or 20 mg/kg S-propafenone prevented exercise-induced CPVT, whereas procainamide (20 mg/kg) or lidocaine (20 mg/kg) were ineffective (n=5 to 9 mice, P<0.05). QRS duration was not significantly different, indicating a similar degree of Na+ channel inhibition. Clinically, propafenone (900 mg/d) prevented ICD shocks in a 22-year-old CPVT patient who had been refractory to maximal standard drug therapy and bilateral stellate ganglionectomy. Conclusions RyR2 cardiac Ca2+ release channel inhibition appears to determine efficacy of class I drugs for the prevention of CPVT in Casq2−/− mice. Propafenone may be an alternative to flecainide for CPVT patients symptomatic on β-blockers.
Objective: Traumatic diaphragmatic rupture (TDR) is a rare but potentially life threatening clinical entity with a high incidence of associated injuries. In this article, our experience with this challenging diagnosis is presented. Methods: In this study, a total of 68 patients with TDR, were operated in our center between July 1994 and September 2005. Study group was analyzed retrospectively. The etiological factors, management and outcomes were discussed. Results: The mean age was 32.9 years with a female to male ratio of 9/59. TDR was right-sided in 16.2% (n = 11) and left-sided in 83.8% (n = 57). The cause of the rupture was penetrating trauma in 51 (75%), and blunt trauma in 17 (25%). Only three patients (4.4%) had late diagnosis. Associated injuries were seen in 91% (n = 62) of the patients. The most common used incision was a laparotomy incision (89.6%). Morbidity and mortality were encountered in 13.1% (n = 9) and 16.2% (n = 11) patients, respectively. Conclusions: Although rare, diaphragmatic rupture must be suspected in any patient with thoracoabdominal injury. Early diagnosis of TDR is sometimes difficult and depends on a high index of suspicion. Surgical repair is necessary even for small tears. The most common approach is the transabdominal approach, which allows a complete exploration of the abdominal organs for associated injuries. The transthoracic approach might be used in most cases with latent diaphragmatic rupture. #
The global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has revealed the urgent need for accurate, rapid, and affordable diagnostic tests for epidemic understanding and management by monitoring the population worldwide. Though current diagnostic methods including real-time polymerase chain reaction (RT-PCR) provide sensitive detection of SARS-CoV-2, they require relatively long processing time, equipped laboratory facilities, and highly skilled personnel. Laser-scribed graphene (LSG)-based biosensing platforms have gained enormous attention as miniaturized electrochemical systems, holding an enormous potential as point-of-care (POC) diagnostic tools. We describe here a miniaturized LSG-based electrochemical sensing scheme for coronavirus disease 2019 (COVID-19) diagnosis combined with three-dimensional (3D) gold nanostructures. This electrode was modified with the SARS-CoV-2 spike protein antibody following the proper surface modifications proved by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) characterizations as well as electrochemical techniques. The system was integrated into a handheld POC detection system operated using a custom smartphone application, providing a user-friendly diagnostic platform due to its ease of operation, accessibility, and systematic data management. The analytical features of the electrochemical immunoassay were evaluated using the standard solution of S-protein in the range of 5.0–500 ng/mL with a detection limit of 2.9 ng/mL. A clinical study was carried out on 23 patient blood serum samples with successful COVID-19 diagnosis, compared to the commercial RT-PCR, antibody blood test, and enzyme-linked immunosorbent assay (ELISA) IgG and IgA test results. Our test provides faster results compared to commercial diagnostic tools and offers a promising alternative solution for next-generation POC applications.
Aspiration of teeth and dental restorations is a recognized, yet an infrequent happening in the literature. Main reasons of aspiration are maxillofacial trauma, dental treatment procedures or ethanol intoxication and dementia. The present case of a 2-unit bridge aspiration is however, not related with any trauma, dental procedure or systemic disease. A 37-year-old male patient had aspirated his bridge while sleeping and the bridge remained unidentified for 1 year despite the radiographic controls. He was then referred to the Chest Diseases Department of School of Medicine, Ege University and the radio-opaque object in the right intermediate bronchus was diagnosed to be an aspirated dental prosthesis. Subsequent to the failure of the rigid bronchoscopy, the patient was referred to the Thoracic Surgery Department and had to be operated for retrieval of the foreign body.
As COVID-19 has reached pandemic status and the number of cases continues to grow, widespread availability of diagnostic testing is critical in helping identify and control the emergence of this rapidly spreading and serious illness. However, a lacking in making a quick reaction to the threat and starting early development of diagnostic sensing tools has had an important impact globally. In this regard, here we will review critically the current developed diagnostic tools in response to the COVID-19 pandemic and compare the different types through the discussion of their pros and cons such as nucleic acid detection tests (including PCR and CRISPR), antibody and protein-based diagnosis tests. In addition, potential technologies that are under development such as on-site diagnosis platforms, lateral flow, and portable PCR units are discussed. Data collection and epidemiological analysis could also be an interesting factor to incorporate with the emerging technologies especially with the wide access to smartphones. Lastly, a SWOT analysis and perspectives on how the development of novel sensory platforms should be treated by the different decision-makers are analyzed.
Point of care (PoC) devices are highly demanding to control current pandemic, originated from severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Though nucleic acid-based methods such as RT-PCR are widely available, they require sample preparation and long processing time. PoC diagnostic devices provide relatively faster and stable results. However they require further investigation to provide high accuracy and be adaptable for the new variants. In this study, laser-scribed graphene (LSG) sensors are coupled with gold nanoparticles (AuNPs) as stable promising biosensing platforms. Angiotensin Converting Enzyme 2 (ACE2), an enzymatic receptor, is chosen to be the biorecognition unit due to its high binding affinity towards spike proteins as a key-lock model. The sensor was integrated to a homemade and portable potentistat device, wirelessly connected to a smartphone having a customized application for easy operation. LODs of 5.14 and 2.09 ng/mL was achieved for S1 and S2 protein in the linear range of 1.0–200 ng/mL, respectively. Clinical study has been conducted with nasopharyngeal swabs from 63 patients having alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2) variants, patients without mutation and negative patients. A machine learning model was developed with accuracy of 99.37% for the identification of the SARS-Cov-2 variants under 1 min. With the increasing need for rapid and improved disease diagnosis and monitoring, the PoC platform proved its potential for real time monitoring by providing accurate and fast variant identification without any expertise and pre sample preparation, which is exactly what societies need in this time of pandemic.
The most important prognostic factor for overall survival was the extent of resection. Further studies with larger numbers of patients are required to confirm the prognostic factors and to obtain a better understanding of the biological behavior of TETs.
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