Publications by authors named "A Thirumal Raj"

1,139 Publications

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Network-constrained technique to characterize pathology progression rate in Alzheimer's disease.

Brain Commun 2021 15;3(3):fcab144. Epub 2021 Jul 15.

Department of Radiology, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.

Current methods for measuring the chronic rates of cognitive decline and degeneration in Alzheimer's disease rely on the sensitivity of longitudinal neuropsychological batteries and clinical neuroimaging, particularly structural magnetic resonance imaging of brain atrophy, either at a global or regional scale. There is particular interest in approaches predictive of future disease progression and clinical outcomes using a single time point. If successful, such approaches could have great impact on differential diagnosis, therapeutic treatment and clinical trial inclusion. Unfortunately, it has proven quite challenging to accurately predict clinical and degeneration progression rates from baseline data. Specifically, a key limitation of the previously proposed approaches for disease progression based on the brain atrophy measures has been the limited incorporation of the knowledge from disease pathology progression models, which suggest a prion-like spread of disease pathology and hence the neurodegeneration. Here, we present a new metric for disease progression rate in Alzheimer that uses only MRI-derived atrophy data yet is able to infer the underlying rate of pathology transmission. This is enabled by imposing a spread process driven by the brain networks using a Network Diffusion Model. We first fit this model to each patient's longitudinal brain atrophy data defined on a brain network structure to estimate a patient-specific rate of pathology diffusion, called the pathology progression rate. Using machine learning algorithms, we then build a baseline data model and tested this rate metric on data from longitudinal Alzheimer's Disease Neuroimaging Initiative study including 810 subjects. Our measure of disease progression differed significantly across diagnostic groups as well as between groups with different genetic risk factors. Remarkably, hierarchical clustering revealed 3 distinct clusters based on CSF profiles with >90% accuracy. These pathological clusters exhibit progressive atrophy and clinical impairments that correspond to the proposed rate measure. We demonstrate that a subject's degeneration speed can be best predicted from baseline neuroimaging volumetrics and fluid biomarkers for subjects in the middle of their degenerative course, which may be a practical, inexpensive screening tool for future prognostic applications.
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http://dx.doi.org/10.1093/braincomms/fcab144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376686PMC
July 2021

Regulation of antioxidant defense and glyoxalase systems in cyanobacteria.

Plant Physiol Biochem 2021 Oct 14;168:353-372. Epub 2021 Oct 14.

Molecular Biology Section, Centre of Advanced Study in Botany, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. Electronic address:

Oxidative stress is common consequence of abiotic stress in plants as well as cyanobacteria caused by generation of reactive oxygen species (ROS), an inevitable product of respiration and photosynthetic electron transport. ROS act as signalling molecule at low concentration however, when its production exceeds the endurance capacity of antioxidative defence system, the organisms suffer oxidative stress. A highly toxic metabolite, methylglyoxal (MG) is also produced in cyanobacteria in response to various abiotic stresses which consequently augment the ensuing oxidative damage. Taking recourse to the common lineage of eukaryotic plants and cyanobacteria, it would be worthwhile to explore the regulatory role of glyoxalase system and antioxidative defense mechanism in combating abiotic stress in cyanobacteria. This review provides comprehensive information on the complete glyoxalase system (GlyI, GlyII and GlyIII) in cyanobacteria. Furthermore, it elucidates the recent understanding regarding the production of ROS and MG, noteworthy link between intracellular MG and ROS and its detoxification via synchronization of antioxidants (enzymatic and non-enzymatic) and glyoxalase systems using glutathione (GSH) as common co-factor.
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http://dx.doi.org/10.1016/j.plaphy.2021.09.037DOI Listing
October 2021

Shear wave elastography to predict oesophageal varices, morbidity and mortality in chronic liver disease.

N Z Med J 2021 Oct 8;134(1543):103-112. Epub 2021 Oct 8.

MBChB, PhD, FRACP, Gastroenterologist, Department of Gastroenterology, Counties Manukau District Health Board, Auckland, New Zealand; Faculty of Medical and Health Sciences University of Auckland, Auckland, New Zealand.

Introduction: In chronic liver disease (CLD), Fibroscan® (transient elastography) can be a useful "rule-out" test for oesophageal varices, but it is limited by body habitus. Shear wave elastography (SWE) is another non-invasive fibrosis test that is better suited for overweight subjects. We determined SWE's ability to predict oesophageal varices, morbidity and mortality in a predominantly overweight population.

Methods: Subjects (n=1,120) with CLD who underwent SWE at Middlemore Hospital between 1 July 2015 and 30 June 2018 were identified. The diagnostic accuracy of SWE to rule out oesophageal varices in advanced hepatic fibrosis was assessed, as well as associations with morbidity and mortality.

Results: Of 304 subjects with advanced fibrosis, 89 had endoscopic data and 18 had varices. Median body mass index was 28.2kg/m2. Area under the receiver operating characteristic curve value for liver stiffness to predict varices was 0.74 and 0.80 when combined with serum albumin. Liver stiffness ≤12.4kPa and albumin ≥37g/L had a negative predictive value of 95%. There were 135 hospital admissions and 19 deaths. Liver stiffness correlated with hospital admissions (p=0.007) and independently predicted mortality.

Conclusions: Shear wave elastography could be a useful rule-out test for screening endoscopy in overweight populations with CLD.
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October 2021

Is only Anterior Stabilization Enough in Three-Column Injury of Subaxial Cervical Spine? - A Long-Term Retrospective Analysis of 78 Patients.

Asian J Neurosurg 2021 Jul-Sep;16(3):512-517. Epub 2021 Sep 14.

Department of Orthopaedics, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India.

Study Design: This was a retrospective study.

Purpose: The purpose was to retrospectively evaluate long-term outcome of anterior stabilization in three-column injury of the subaxial cervical spine.

Overview Of Literature: Literature shows varied results regarding the approach to be chosen. Most studies prefer a combined approach since biomechanically forms more stable construct. The isolated posterior approach is preferred by many as it is easy to reduce and fix three-column injuries. There are very few studies which show the isolated anterior approach to be better than the other two.

Materials And Methods: Seventy-eight patients of three-column injury operated by anterior approach with follow-up of atleast 2 years were included and retrospectively analyzed. Clinical data included age, sex, time to surgery, methods of reduction, postoperative mobilization, and neurological evaluation using the ASIA scale. Radiological data included pre- and postreduction X-ray, computed tomography, and magnetic resonance imaging (MRI). X-rays taken post-operatively at 1,3, 6 months, 1yr and 2yrs. Variables like fracture type (AO Classification), overall alignment, localized kyphosis, time for fusion and grade of fusion mass were noted.

Results: Of 78 patients, 61 had bifacetal dislocation and 17 unifacetal. The most common site was C5-6, followed by C3-4 and C6-7. The mean patient age was 35.98 years with 60 males and 18 females. The mean time to surgery was 4.4 days. Forty dislocations were reduced by closed method and 38 by open anterior approach. Fifty-six percent of patients had traumatic disc injury on MRI. All are managed by single-level anterior cervical discectomy and fusion with iliac crest autograft for fusion. The mean preoperative lordosis: 4.44° (range -13.4° to 25°) and mean postoperative lordosis: 28.57° ( < 0.0001) mean loss of alignment: 2.59° by 2 years, 100% fusion with mean time - 22.82 weeks, neurological recovery in 34.6% with atleast one grade improvement in ASIA scale. No neurological worsening or need for revision surgery was observed.

Conclusion: The goal of surgery in cervical injury is bony stabilization and fusion using a least morbid approach and one with good long-term outcome. Above study concludes that only anterior stabilization after reduction of three-column injury would suffice with good long-term outcome, thereby obviating need for global fusion.
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http://dx.doi.org/10.4103/ajns.AJNS_518_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477831PMC
September 2021

Evaluation of the Effect of Long-term Use of Three Intracanal Medicaments on the Radicular Dentin Microhardness and Fracture Resistance: An study.

Acta Stomatol Croat 2021 Sep;55(3):291-301

Department of Oral and Maxillofacial Sciences, Sapienza University, University of Rome, Italy.

Objectives: The aim of this research was to evaluate the effect of long-term use of three intracanal medicaments on the radicular dentin microhardness and fracture resistance.

Material And Methods: A chemomechanical preparation was done using the Protaper rotary instruments up to F3. The teeth were stored in an incubator at 37°C at 100% humidity and were categorized in three groups by random allocation, namely: Triple Antibiotic Paste (TAP), Calcium hydroxide paste (Apexcal) and Ledermix. Following medicament application, the access openings of all teeth were sealed with 4 mm thickness of cavit. The samples were stored for periods of 1 week, 1 month and 3months. Two dentin cylinders measuring 5mm and 3mm were obtained from each sample. The cervical third was used for fracture resistance and the middle third was used for micro hardness evaluation. The microhardness testing was done using a Knoop microhardness tester, and the fracture resistance testing was done using the universal testing machine.

Results: Calcium hydroxide showed maximally negative effect on the physical properties of radicular dentin compared to TAP (p= 0.0100 at one month and Ledermix (p=0.0001 at one month). With an increase in the application time, there was an increased deterioration in the physical properties of radicular dentin.

Conclusion: Long-term placement of calcium hydroxide, Triple Antibiotic Paste, and Ledermix (p= 0.0001at 3 months) significantly affects the microhardness and fracture resistance of radicular dentin.
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http://dx.doi.org/10.15644/asc55/3/6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514225PMC
September 2021
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