DTI of the Visual Pathway - White Matter Tracts and Cerebral Lesions

DTI is a technique that identifies white matter tracts (WMT) non-invasively in healthy and non-healthy patients using diffusion measurements. Similar to visual pathways (VP), WMT are not visible with classical MRI or intra-operatively with microscope. DTI will help neurosurgeons to prevent destruction of the VP while removing lesions adjacent to this WMT. We have performed DTI on fifty patients before and after surgery between March 2012 to January 2014. To navigate we used a 3DT1-weighted sequence. Additionally, we performed a T2-weighted and DTI-sequences. The parameters used were, FOV: 200 x 200 mm, slice thickness: 2 mm, and acquisition matrix: 96 x 96 yielding nearly isotropic voxels of 2 x 2 x 2 mm. Axial MRI was carried out using a 32 gradient direction and one b0-image. We used Echo-Planar-Imaging (EPI) and ASSET parallel imaging with an acceleration factor of 2 and b-value of 800 s/mm². The scanning time was less than 9 min.The DTI-data obtained were processed using a FDA approved surgical navigation system program which uses a straightforward fiber-tracking approach known as fiber assignment by continuous tracking (FACT). This is based on the propagation of lines between regions of interest (ROI) which is defined by a physician. A maximum angle of 50, FA start value of 0.10 and ADC stop value of 0.20 mm²/s were the parameters used for tractography.There are some limitations to this technique. The limited acquisition time frame enforces trade-offs in the image quality. Another important point not to be neglected is the brain shift during surgery. As for the latter intra-operative MRI might be helpful. Furthermore the risk of false positive or false negative tracts needs to be taken into account which might compromise the final results.     

Discovery of putative breast cancer antigens using an integrative platform of genomics‐driven immunoproteomics

Recent advances in cancer immuno‐therapeutics such as checkpoint inhibitors, chimeric antigen‐receptor T cells, and tumor infiltrating T cells (TIL) are now significantly impacting cancer patients in a positive manner. Although very promising, reports indicate no more than 25% of cases result in complete remission. One of the limitations of these treatments is the identity of putative cancer antigens in each patient, as it is technically challenging to identify cancer antigens in a rapid fashion. Thus, identification of cancer antigens followed by targeted treatment will increase the efficacy of cancer immunotherapies. To achieve this goal, a combined technologies platform of deep genomic sequencing and personalized immune assessment was devised, termed G enomics D riven I mmunoproteomics (GDI). Using this technological platform, we report the discovery of 149 tumor antigens from human breast cancer patients. Significant number of these putative cancer antigens arise from single nucleotide variants (SNVs), as well as insertions and deletions that results into frame‐shift mutations. We propose a general model of anti‐cancer immunity and suggest that the GDI platform may help identify patient‐specific tumor antigens in a timely fashion for precision immunotherapies.     

Engineering and introduction of <Emphasis Type="Italic">de novo</Emphasis> disulphide bridges in organophosphorus hydrolase enzyme for thermostability improvement

The organophosphorus hydrolase (OPH) has been used to degrade organophosphorus chemicals, as one of the most frequently used decontamination methods. Under chemical and thermal denaturing conditions, the enzyme has been shown to unfold. To utilize this enzyme in various applications, the thermal stability is of importance. The engineering of de novo disulphide bridges has been explored as a means to increase the thermal stability of enzymes in the rational method of protein engineering. In this study, Disulphide by Design software, homology modelling and molecular dynamics simulations were used to select appropriate amino acid pairs for the introduction of disulphide bridge to improve protein thermostability. The thermostability of the wild-type and three selected mutant enzymes were evaluated by half-life, ΔG inactivation (ΔGi) and structural studies (fluorescence and far-UV CD analysis). Data analysis showed that half-life of A204C/T234C and T128C/E153C mutants were increased up to 4 and 24 min, respectively; however, for the G74C/A78C mutant, the half-life was decreased up to 9 min. For the T128C/E124C mutant, both thermal stability and Catalytic efficiency (kcat) were also increased. The half-life and ΔGi results were correlated to the obtained information from structural studies by circular dichroism (CD) spectrometry and extrinsic fluorescence experiments; as rigidity increased in A204C/T2234C and T128C/E153C mutants, half-life and ΔGi also increased. For G74C/A78C mutant, these parameters decreased due to its higher flexibility. The results were submitted a strong evidence for the possibility to improve the thermostability of OPH enzyme by introducing a disulphide bridge after bioinformatics design, even though this design would not be always successful.     

The Benefit of Atrioventricular Junction Ablation for Permanent Atrial Fibrillation and Heart Failure Patients Receiving Cardiac Resynchronization Therapy: An Updated Systematic Review and Meta-analysis

BackgroundAtrial fibrillation (AF) is correlated with a poor biventricular pacing and inadequate response to cardiac resynchronization therapy (CRT). Biventricular pacing improvement can be achieved by conducting the atrioventricular junction ablation (AVJA). We aimed to investigate the benefit of AVJA for permanent AF and heart failure with reduced ejection fraction (HFrEF) patients receiving CRT.MethodsIn August 2020, a systematic review and meta-analysis study comparing CRT plus AVJA versus CRT for permanent AF and HFrEF patients was conducted. Relevant articles were identified through the electronic scientific database such as ClinicalTrials.gov, ProQuest, ScienceDirect, PubMed, and Cochrane. The pooled risk ratio (RR) and pooled mean difference (MD) were estimated.ResultsA total of 3199 patients from 14 cohort studies were involved in this study. Additional AVJA reduced cardiovascular mortality (RR = 0.75, 95% confidence interval [CI] = 0.61 to 0.93, P < 0.01) in permanent AF and HFrEF patients receiving CRT. Biventricular pacing rate was higher in CRT plus AVJA group (MD = 8.65%, 95% CI = 5.62 to 11.67, P < 0.01) than in CRT alone group. The reverse remodeling characterized by the reduction of left ventricular end-diastolic diameter (LVEDD) was greater in the CRT plus AVJA group (MD = ?2.11 mm, 95% CI = ?3.79 to ?0.42, P = 0.01).ConclusionIn permanent AF and HFrEF patients receiving CRT, AVJA effectively increased the biventricular pacing rate. Adequate biventricular pacing rate provided a better response to the CRT marked by the greater ventricular reverse remodeling and survival from cardiovascular mortality.     

The genotoxicity study of garlic and pasipy herbal drops by peripheral blood micronucleus test

The in vivo rodent micronucleus test is widely used as a genotoxic assay to detect the clastogenic activity of chemicals. In this research the genotoxic effects of herbal drops of garlic and pasipy were evaluated using the micronucleus test. Maximum Tolerated Dose (MTD) was determined by a dose-response test. For each medicine three treatment groups were considered with doses of MTD, 1/2 MTD and 1/4 MTD according to the CSGMT protocol (1995 Japan). Drugs were administered orally to mice (test groups). Mitomicin C was used as a known genotoxic agent in positive control group. The peripheral blood samples before treatment (zero time samples) were considered as negative control. The appearance of a micronucleus is used as an index for genotoxic potential. The results obtained indicated that the herbal drops showed genotoxicity effect and it was dose-dependent compared to the negative control group. This genotoxicity was significant (p < 0.05) but the genotoxic effects of garlic and pasipy were "not significant" compared to the historical negative control group (p > 0.05). Therefore our results if compared to the negative control group is significant and it is worthy of consideration.