Evaluation of anatomical and visual function for early detection of ethambutol toxicity among tuberculosis patients

AIM: To evaluate if early ethambutol toxicity can be detected by comparing pre - and post - treatment anatomical and visual function using retinal nerve fiber thickness, pattern visual evoked potentials and conventional optic nerve function tests. METHODS:This was a prospective study involving 72 eyes of 36 patients treated with ethambutol according to directly observed treatment short-course(DOTS) strategy in Hospital Universiti Sains Malaysia, Kelantan, Malaysia. The visual acuity and optic nerve function tests were performed by a single investigator. Likewise, Humphrey automated perimetry, optical coherence tomography ( OCT ) measurement of the retinal nerve fibre layer (RNFL) and pattern visual evoked potential (PVEP) were performed by a single technician. The examinations were performed before initiating ethambutol treatment and 3mo after that. RESULTS: There was no change in visual acuity, colour vision, light brightness, red saturation and fundus findings pre and post ethambutol. However, there was a statistically significant deterioration in the mean deviation of the visual field post treatment (P = 0. 010). There were also significant changes on OCT and PVEP, with increased RNFL thickness in all quadrants ( P < 0. 05 ) and PVEP delayed P100 peak latency and amplitude (P<0. 001). CONCLUSION: Ethambutol toxicity is a known complication of tuberculosis treatment. Early detection of this toxicity may prevent severe irreversible visual loss. The use of OCT to detect RNFL thickness and PVEP to assess P100 latency and amplitude can assist in the detection of subclinical anatomical and visual function changes prior to development of abnormalities on conventional optic nerve function tests

Targeted inactivation of Salmonella Agona metabolic genes by group II introns and in vivo assessment of pathogenicity and anti-tumour activity in mouse model

The fight against cancer has been a never-ending battle. Limitations of conventional therapies include lack of selectivity, poor penetration and highly toxic to the host. Using genetically modified bacteria as a tumour therapy agent has gained the interest of scientist from the past few decades. Low virulence and highly tolerability of Salmonella spp. in animals and humans make it as the most studied pathogen with regards to anti-tumour therapy. The present study aims to construct a genetically modified S. Agona auxotroph as an anti-tumour agent. LeuB and ArgD metabolic genes in ΔSopBΔSopD double knockout S. Agona were successfully knocked out using a Targetron gene knockout system. The knockout was confirmed by colony PCR and the strains were characterized in vitro and in vivo. The knockout of metabolic genes causes significant growth defect in M9 minimal media. Quadruple knockout ΔSopBΔSopDΔLeuBΔArgD (BDLA) exhibited lowest virulence among all of the strains in all parameters including bacterial load, immunity profile and histopathology studies. In vivo anti-tumour study on colorectal tumour bearing-BALB/c mice revealed that all strains of S. Agona were able to suppress the growth of the large solid tumour as compared with negative control and ΔLeuBΔArgD (LA) and BDLA auxotroph showed better efficacy. Interestingly, higher level of tumour growth suppression was noticed in large tumour. However, multiple administration of bacteria dosage did not increase the tumour suppression efficacy. In this study, the virulence of BDLA knockout strain was slightly reduced and tumour growth suppression efficacy was successfully enhanced, which provide a valuable starting point for the development of S. Agona as anti-tumour agent

Targeted inactivation of Salmonella Agona metabolic genes by group II introns and in vivo assessment of pathogenicity and anti-tumour activity in mouse model

The fight against cancer has been a never-ending battle. Limitations of conventional therapies include lack of selectivity, poor penetration and highly toxic to the host. Using genetically modified bacteria as a tumour therapy agent has gained the interest of scientist from the past few decades. Low virulence and highly tolerability of Salmonella spp. in animals and humans make it as the most studied pathogen with regards to anti-tumour therapy. The present study aims to construct a genetically modified S. Agona auxotroph as an anti-tumour agent. LeuB and ArgD metabolic genes in ΔSopBΔSopD double knockout S. Agona were successfully knocked out using a Targetron gene knockout system. The knockout was confirmed by colony PCR and the strains were characterized in vitro and in vivo. The knockout of metabolic genes causes significant growth defect in M9 minimal media. Quadruple knockout ΔSopBΔSopDΔLeuBΔArgD (BDLA) exhibited lowest virulence among all of the strains in all parameters including bacterial load, immunity profile and histopathology studies. In vivo anti-tumour study on colorectal tumour bearing-BALB/c mice revealed that all strains of S. Agona were able to suppress the growth of the large solid tumour as compared with negative control and ΔLeuBΔArgD (LA) and BDLA auxotroph showed better efficacy. Interestingly, higher level of tumour growth suppression was noticed in large tumour. However, multiple administration of bacteria dosage did not increase the tumour suppression efficacy. In this study, the virulence of BDLA knockout strain was slightly reduced and tumour growth suppression efficacy was successfully enhanced, which provide a valuable starting point for the development of S. Agona as anti-tumour agent

Identifcation of reference genes in chicken intraepithelial lymphocyte natural killer cells infected with very-virulent infectious bursal disease virus

Due to the limitations in the range of antibodies recognising avian viruses, quantitative real-time PCR (RT-qPCR) is still the most widely used method to evaluate the expression of immunologically related genes in avian viruses. The objective of this study was to identify suitable reference genes for mRNA expression analysis in chicken intraepithelial lymphocyte natural killer (IEL-NK) cells after infection with very-virulent infectious bursal disease virus (vvIBDV). Fifteen potential reference genes were selected based on the references available. The coefcient of variation percentage (CV%) and average count of these 15 genes were determined by NanoString technology for control and infected samples. The M and V values for shortlisted reference genes (ACTB, GAPDH, HMBS, HPRT1, SDHA, TUBB1 and YWHAZ) were calculated using geNorm and NormFinder. GAPDH, YWHAZ and HMBS were the most stably expressed genes. The expression levels of three innate immune response related target genes, CASP8, IL22 and TLR3, agreed in the NanoString and RNA sequencing (RNA-Seq) results using one or two reference genes for normalisation (not HMBS). In conclusion, GAPDH and YWHAZ could be used as reference genes for the normalisation of chicken IEL-NK cell gene responses to infection with vvIBDV

Extraction of fresh banana waste juice as non-cellulosic and non-food renewable feedstock for direct lipase production

The bulk availability of banana waste in the world has made a move towards the development of alternative novel renewable sugars in present study as the pressed juice from banana frond and pseudostem was found to contain high level of renewable sugars such as glucose, sucrose and fructose. By using a simple sugarcane press, the glucose content in the banana frond juice was 16.6 g/L, which accounts for 55% of the total fermentable sugars. From the results, the lipase production reached ∼200 U/mL in medium comprising banana frond juice and banana pseudostem juice, comparable to basal medium with glucose (206.3 U/mL) as carbon source in basal media. As banana pseudostem possesses high content of starch, microwave heating pretreatment showed 36% enhancement of glucose content (10.4 g/L) in juice as compared to direct pressed juice (7.78 g/L). This result indicates that banana waste juice can be used as an alternative fermentable carbon source for lipase production and has potential as a fermentable carbon source

Incidence of acute cerebrovascular events in patients with rheumatic or calcific mitral stenosis: a systematic review and meta-analysis

Background Patients with mitral stenosis (MS) may be predisposed to acute cerebrovascular events (ACE) and peripheral thromboembolic events (TEE). Concomitant atrial fibrillation (AF), mitral annular calcification (MAC) and rheumatic heart disease (RHD) are independent risk factors. Our aim was to evaluate the incidence of ACEs in MS patients and the implications of AF, MAC, and RHD on thromboembolic risks. Methods This systematic review was registered on PROSPERO (CRD42021291316). Six databases were searched from inception to 19th December 2021. The clinical outcomes were composite ACE, ischaemic stroke/transient ischaemic attack (TIA), and peripheral TEE. Results We included 16 and 9 papers, respectively, in our qualitative and quantitative analyses. The MS cohort with AF had the highest incidence of composite ACE (31.55%; 95%CI 3.60-85.03; I 2 =99%), followed by the MAC (14.85%; 95%CI 7.21-28.11; I 2 =98%), overall MS (8.30%; 95%CI 3.45-18.63; I 2 =96%) and rheumatic MS population (4.92%; 95%CI 3.53-6.83; I 2 =38%). Stroke/TIA were reported in 29.62% of the concomitant AF subgroup (95%CI 2.91-85.51; I 2 =99%) and in 7.11% of the overall MS patients (95%CI 1.91-23.16; I 2 =97%). However, the heterogeneity of the pooled incidence of clinical outcomes in all groups, except the rheumatic MS group, were substantial and significant. The logit-transformed proportion of composite ACE increased by 0.0141 (95% CI 0.0111-0.0171; p<0.01) per year of follow-up. Conclusion In the MS population, MAC and concomitant AF are risk factors for the development of ACE. The scarcity of data in our systematic review reflects the need for further studies to explore thromboembolic risks in all MS subtypes

Evaluation of optic nerve head and macula parameters pre-and post external beam radiotherapy in patient with head and neck tumor

Head and neck cancers is one of the tenth most common cancer worldwide with high mortality and morbidity rate. Due to its location, surgical clearance is often difficult and require radiotherapy and chemotherapy to achieve locoregional control. Therefore, radiotherapy is considered the mainstay treatment in head and neck cancers. Despite advancement of laser beam, radiation protocol and protective equipment, radiation damage to surrounding normal tissue is inevitable. Radiation optic neuropathy and retinopathy are known ocular complication following radiotherapy. Early detection and prompt early treatment might prevent debilitating visual loss. Optical coherence tomography of macula and optic nerve head parameters will be able to provide an objective measurement and evaluation of above areas. Objectives: Our objective of this study is to compare mean macular thickness and optic nerve head parameters pre-and six-month post external beam radiotherapy in patient with head and neck tumours. Methods: A cross sectional study involving 30 patients histologically diagnosed head and neck cancers. Patient who fulfilled inclusion and exclusion criteria were recruited from a single centre in Malaysia. Recruitment was carried out between December 2016 and August 2017. Evaluation of optic nerve head parameters and macular thickness were conducted using Spectral Domain-Cirrus optical coherence tomography. Optic nerve head parameters, retinal nerve fibre layer (RNFL) thickness and macular thickness were evaluated prior to radiotherapy. A repeat procedure was conducted six months post external beam irradiation. Assuming both eye received similar radiation exposure, right eye ONH parameters and macular thickness are analysed and discussed in this study. Descriptive analysis, paired t-test and multivariate ANCOVA method is performed in this study using SPSS. Result: Macular is thinner in post radiotherapy, but without statistically significant. There were no changes in mean optic nerve head parameters between pre-and post radiotherapy period. Mean RNFL thickness showed thickening in the post radiotherapy period. Temporal and inferior quadrant of RNFL showed thickening in post radiotherapy period, in which inferior quadrant showed statistically significant result. Conclusion: There was thinning of macular thickness and thickening of optic nerve head RNFL in six-month post radiotherapy. But the changes were small and it is too early to justify the parameters. Further researches, larger studies and longer follow up period need to be conducted before we can further draw the conclusion of other parameters related to early exposure to radiation

Driving profile modeling and recognition based on soft computing approach

Advancements in biometrics-based authentication have led to its increasing prominence and are being incorporated into everyday tasks. Existing vehicle security systems rely only on alarms or smart card as forms of protection. A biometric driver recognition system utilizing driving behaviors is a highly novel and personalized approach and could be incorporated into existing vehicle security system to form a multimodal identification system and offer a greater degree of multilevel protection. In this paper, detailed studies have been conducted to model individual driving behavior in order to identify features that may be efficiently and effectively used to profile each driver. Feature extraction techniques based on Gaussian mixture models (GMMs) are proposed and implemented. Features extracted from the accelerator and brake pedal pressure were then used as inputs to a fuzzy neural network (FNN) system to ascertain the identity of the driver. Two fuzzy neural networks, namely, the evolving fuzzy neural network (EFuNN) and the adaptive network-based fuzzy inference system (ANFIS), are used to demonstrate the viability of the two proposed feature extraction techniques. The performances were compared against an artificial neural network (NN) implementation using the multilayer perceptron (MLP) network and a statistical method based on the GMM. Extensive testing was conducted and the results show great potential in the use of the FNN for real-time driver identification and verification. In addition, the profiling of driver behaviors has numerous other potential applications for use by law enforcement and companies dealing with buses and truck drivers

Automatic 4D reconstruction of patient-specific cardiac mesh with 1-to-1 vertex correspondence from segmented contours lines.

We propose an automatic algorithm for the reconstruction of patient-specific cardiac mesh models with 1-to-1 vertex correspondence. In this framework, a series of 3D meshes depicting the endocardial surface of the heart at each time step is constructed, based on a set of border delineated magnetic resonance imaging (MRI) data of the whole cardiac cycle. The key contribution in this work involves a novel reconstruction technique to generate a 4D (i.e., spatial-temporal) model of the heart with 1-to-1 vertex mapping throughout the time frames. The reconstructed 3D model from the first time step is used as a base template model and then deformed to fit the segmented contours from the subsequent time steps. A method to determine a tree-based connectivity relationship is proposed to ensure robust mapping during mesh deformation. The novel feature is the ability to handle intra- and inter-frame 2D topology changes of the contours, which manifests as a series of merging and splitting of contours when the images are viewed either in a spatial or temporal sequence. Our algorithm has been tested on five acquisitions of cardiac MRI and can successfully reconstruct the full 4D heart model in around 30 minutes per subject. The generated 4D heart model conforms very well with the input segmented contours and the mesh element shape is of reasonably good quality. The work is important in the support of downstream computational simulation activities