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Robotic-assisted beating heart surgery provides precise repair of periprosthetic mitral valvular leak
No full textThe prosthetic paravalvular leak is a rare but important complication following mitral valve replacement. Determining the location of the leak is almost always dependent on perioperative transoesophageal echocardiography and the considerable expertise of echo operators. Acoustic shadowing due to the prosthetic valve may create another important difficulty. In this report, we present a case with a paravalvular leak diagnosed 1 year after mitral valve replacement. Beating heart surgery and robotic 3D/high-resolution camera provided to localize the direct location of leak coherent with perioperative echocardiography and precise repair. The robotic approach prevented the potential complications of aortic cross-clamp and resternotomy. The paravalvular leak is one of the most important complications of mitral valve replacement surgery with a prevalence of 2-13\% {[}1, 2].3AUG 33
Dosimetric evaluation of VMAT and helical tomotherapy techniques comparing conventional volumes with clinical target volumes based on new ESTRO ACROP post-mastectomy with immediate implant reconstruction contouring guidelines
No full textBackground The ESTRO-ACROP Consensus Guideline (EACG) recommends implant excluded clinical target volume (CTVp) definitions for post-mastectomy radiation therapy after implant-based immediate breast reconstruction (IBR). The purpose of this study is to investigate the effectiveness of Helical Tomotherapy (HTp) and Volumetric Modulated Arc Therapy (VMATp) treatment techniques in terms of CTVp coverage and reduced organ at risk (OAR), normal tissue and implant doses when CTVp was used for treatment planning as the target structure instead of conventional CTV. Methods Eight left-sided and eight right-sided breast cancer patients who underwent IBR after mastectomy were included in this study. Planning CT data sets were acquired during free breathing and patients were treated with HT technique targeted to conventional CTV. Retrospectively, CTVp was delineated based on EACG by the same radiation oncologist, and treatment plans with HTp and VMATp techniques were generated based on CTVp. For each patient, relevant dosimetric parameters were obtained from three different treatment plans. Results There was no statistically significant difference on target coverage in terms of, PTVp-D95, PTVp-Vpres, homogeneity index (p > 0.05) between HTp and VMATp plans. But, the conformity numbers were significantly higher (HTp vs VMATp, 0.69 +/- 0.15 vs 0.79 +/- 0.12) for VMATp (Z = - 2.17, p = 0.030). While HTp significantly lowered Dmax and Dmean for LAD (LAD-D-max: chi(2) = 12.25, p = 0.002 and LAD-D-mean: chi(2) = 12.30, p = 0.002), neither HTp nor VMATp could reduce maximum and mean dose to heart (p > 0.05). Furthermore, heart volume receiving 5 Gy was significantly higher for VMATp when compared to HTp (21.2 +/- 9.8 vs 42.7 +/- 24.8, p: 0.004). Both techniques succeeded in reducing the mean dose to implant (HTp vs HT, p < 0.001VMATp vs HT, p < 0.001VMATp vs HTp, p = 0.005). Conclusion Both HTp and VMATp techniques succeeded to obtain conformal and homogeneous dose distributions within CTVp while reducing the mean implant dose. HTp was found to be superior to VMATp with regards to lowering all OAR doses except for CB.1OCT 211
Circulating Dynamics of SARS-CoV-2 Variants between April 2021 and February 2022 in Turkey
No full textThe diagnosis of new variants and monitoring their potential effects on diagnosis, therapeutics, and vaccines by genomic sequencing is essential to manage global public crises. In the current study, spike-genome next-generation sequencing was generated from 492 SARS-CoV-2 isolates to evaluate the mutations in Turkey from April 2021 to February 2022. The variant analysis was performed using (Coronavirus Antiviral and Resistance Database (CoV-RDB) by Stanford University). We revealed that the lineages Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), Eta (B.1.525), variant of interest (VOI), lota (B.1.526), Zeta (P.2), Omicron (B.1.1.529), and Omicron BA.1 (B.1.1.529.1) were in the circulation in Turkey during the given period. The most common lineages were B.1.1.7, B.1.617.2, B.1.1.529, and B.1.1.529.1 SARS-CoV-2 variant circulation in Turkey seems highly heterogenetichowever, quite similar to the global epidemiologic analysis. The existence of globally circulating variants in the same chronological order in Turkey can be a guide for precautions, treatment, and vaccine options to be taken in the future.OCT 15202
Targeting SARS-CoV-2 infection through CAR-T-like bispecific T cell engagers incorporating ACE2
No full textObjectives. Despite advances in antibody treatments and vaccines, COVID-19 caused by SARS-CoV-2 infection remains a major health problem resulting in excessive morbidity and mortality and the emergence of new variants has reduced the effectiveness of current vaccines. Methods. Here, as a proof-of-concept, we engineered primary CD8 T cells to express SARS-CoV-2 Spike protein-specific CARs, using the extracellular region of ACE2 and demonstrated their highly specific and potent cytotoxicity towards Spike-expressing target cells. To improve on this concept as a potential therapeutic, we developed a bispecific T cell engager combining ACE2 with an anti-CD3 scFv (ACE2-Bite) to target infected cells and the virus. Results. As in CAR-T cell approach, ACE2-Bite endowed cytotoxic cells to selectively kill Spike-expressing targets. Furthermore, ACE2-Bite neutralized the pseudoviruses of SARS-CoV, SARS-CoV-2 wild-type, and variants including Delta and Omicron, as a decoy protein. Remarkably, ACE2-Bite molecule showed a higher binding and neutralization affinity to Delta and Omicron variants compared to SARS-CoV-2 wild-type Spike proteins. Conclusion. In conclusion, these results suggest the potential of this approach as a variant-proof, therapeutic strategy for future SARS-CoV-2 variants, employing both humoral and cellular arms of the adaptive immune response.101
Potential Neurotoxic Effects of Glioblastoma-Derived Exosomes in Primary Cultures of Cerebellar Neurons via Oxidant Stress and Glutathione Depletion
No full textHigh-grade gliomas are the most fatal brain tumors. Grade 4 gliomas are called glioblastoma multiforme (GBM), which are associated with the poorest survival and a 5-year survival rate of less than 4\%. Many patients with GBM developed concomitant cognitive dysfunctions and epilepsy. Although the cognitive decline is well defined in glioblastomas, the neurotoxic factors underlying this pathology are not well understood in GBM patients. In this study, we aimed to investigate whether GBM-derived exosomes play a role in neuronal toxicity. For this purpose, exosomes obtained from T98G and U373 GBM cells were applied to primary neuron culture at different concentrations. Subsequently, MTT, LDH, GSH, TAS, and TOS tests were performed. Both GBM-derived exosomes induced a dose-dependent and statistically significant increase of LDH release in cerebellar neurons. MTT assay revealed as both T98G and U373 GBM-derived exosomes induced dose-dependent neurotoxic effects in cerebellar neurons. To the best of our knowledge, this study is the first study demonstrating the toxic potential of GBM-derived exosomes to primary neurons, which may explain the peritumoral edema and cognitive decline in GBM patients.7JUL1
Loop nerve graft prefabrication for peripheral nerve defect reconstruction
No full textBACKGROUND: Delayed autologous nerve graft reconstruction is inevitable in devastating injuries. Delayed or prolonged repair time has deleterious effects on nerve grafts. We aimed improving and accelerating nerve graft reconstruction process in a rat long nerve defect model with loop nerve graft prefabrication particularly to utilize for injuries with tissue loss. METHODS Twenty-four Sprague-Dawley rats were allocated into three groups. 1.5 cm long peroneal nerve segment was excised, reversed in orientation, and used as autologous nerve graft. In conventional interpositional nerve graft group (Group 1), nerve defects were repaired in single-stage. In loop nerve graft prefabrication group (Group 2), grafts were sutured end-to-end (ETE) to the proximal peroneal nerve stumps. Distal ends of the grafts were sutured end-to-side to the peroneal nerve stumps 5 mm proximal to the ETE repair sites in first stage. In second stage, distal ends of the prefabricated grafts were transposed and sutured to distal nerve stumps. In staged conventional interpositional nerve graft group (Group 3), grafts were sutured ETE to proximal peroneal nerve stumps in first stage. Distal ends of the grafts and nerve stumps were tacked to the surrounding muscles until the final repair in second stage. Followup period was 4 weeks for each stage in Groups 2 and 3, and 8 weeks for Group 1. Peroneal function index (PFI), electrophysiology, and histological assessments were conducted after 8 weeks. P0.05). Group 3 (-33.64 +/- 6.4) had a statistical difference compared to other groups (p0.05), whereas both groups had a statistical difference compared to Group 3 (10.44 +/- 1.96 mV/ 1.51 +/- 0.15 ms) (p0.05), whereas both groups had significantly poor axon counts compared to Group 2 (2531 +/- 91.18) (p<0.05). CONCLUSION. Loop nerve graft prefabrication improved axonal regeneration without delay. Loop prefabrication can accelerate prolonged regeneration time for the injuries indicating a delayed nerve reconstruction. Higher axon counts derived with loop nerve prefabrication may even foster its investigation in immediate long nerve defect reconstructions in further studies.8AUG1043-10512
Turkish Validity and Reliability of the Satisfaction with Simulation Experience Scale
No full textObjective: Research on simulation-based experience focuses primarily on the student's level of knowledge, skills, self-confidence, and satisfaction. There is only one scale in Turkish that can be used to measure satisfaction with the simulation experience. The aim of this study was to establish the validity and reliability of the Turkish version of the Satisfaction with Simulation Experience Scale (SSES).Methods: The study sample consisted of 130 nursing students from two universities. Data were collected using a student information form, the Turkish version of the Satisfaction with Simulation Experience Scale (SSES-TR) and the Scale of Student Satisfaction and Confidence in Learning (SSSCL). The original SSES was translated into Turkish. Thirteen academics, who were experts in nursing and simulation, were consulted for content validity. Expert feedback was collected in a form to determine the content validity ratio using Lawshe's technique. The Turkish adaptation of the SSES was performed by four linguists to ensure linguistic validity. The correlation between the SSES-TR and SSSCL was determined using concurrent validity and Pearson's Correlation. Internal consistency tests were used to test reliability. The SSES-TR was administered to 35 students as a test-retest with an interval of two weeks to determine its consistency across time. Construct validity was evaluated by confirmatory factor analysis (CFA).Results: The scale had a content validity index (CVI) of 0.86. The SSES-TR had a Cronbach's alpha (alpha) of 0.928. The correlation between SSES-TR items and total and subscale scores ranged from 0.492 to 0.749. Test-retest reliability coefficients showed that the SSES-TR total score and subscale scores were compatible. The fit statistics of the 3-factor scale structure according to CFA are at the level of ``acceptable fit{''} according to RMSEA (0.095) and SRMR (0.090).Conclusions: The SSES-TR is a reliable and valid measure that can be used to assess nursing students' satisfaction with simulation-based experience.3461-4681
A Case With New-Onset Neuromyelitis Optica Spectrum Disorder Following COVID-19 mRNA BNT162b2 Vaccination
No full textIntroduction: In the midst of the coronavirus disease of 2019 pandemic, active immunization by effective vaccination gained utmost importance in terms of global health. The messenger RNA (mRNA) vaccines are novel strategies requiring clinical surveillance for adverse events. Case Report: We report a 43-year-old previously healthy female with an optic neuritis attack 24 hours following immunization with the second dose of coronavirus disease of 2019 mRNA BNT162b2 vaccine. A second transverse myelitis attack together with an elevated anti-AQP-4 antibody titer confirmed the diagnosis of neuromyelitis optica spectrum disorder. Conclusion: Our case identifies the BNT162b2 vaccine as a possible trigger for neuromyelitis optica spectrum disorder. This rare and potentially coincidental event has no implications for vaccine administration practices. However, further research is needed to elucidate the effects of mRNA vaccines on humoral and cell-mediated immunity.3MAY147-1502
Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus
No full textCrimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40\% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains. There are currently no approved treatments for Crimean-Congo Hemorrhagic Fever Virus (CCHFV) infection. In this study, the authors structurally characterize the epitope targeted by protective non-neutralizing mouse and human antibodies and provide insights into their broad range potential against various CCHFV strains.1NOV 261
