Blood and cerebrospinal fluid biomarkers for Alzheimer’s disease: from clinical to preclinical cohorts

Dementia is a major contributor to global morbidity, mortality and costs associated with health and social care. Alzheimer’s disease (AD) is a common pathology culminating in dementia, but it has a preclinical phase of one to two decades, with early brain deposition of amyloid and tau, followed by synaptic and neuronal degeneration. Early detection during the preclinical phase of AD might enable disease-modifying therapies to be applied during a window of opportunity in which they would be more likely to work. Currently the main biomarkers of AD pathology are neuroimaging markers, which can be costly, or cerebrospinal fluid markers, which require invasive sampling. Blood biomarkers would be relatively less invasive and could be a more cost-effective means for risk stratification, early detection, monitoring progression and measuring response to treatment. The work described here used sensitive assay technology including the Simoa digital immunoassay platform, in large and well-characterised cohorts, to examine candidate blood biomarkers linked to the core AD pathologies of amyloid, tau and neurodegeneration, as specified by the National Institute on Aging and Alzheimer’s Association 2018 research framework. Firstly, experiments on samples from a cognitive clinic cohort established the stability of the blood biomarkers Aβ40, Aβ42, total tau and neurofilament light chain (NFL – a marker of neurodegeneration) to multiple freeze-thaw cycles, and the optimal blood fraction to use for quantifying each of these biomarkers in onward studies. Secondly, an unique large preclinical cohort with life course data (Insight 46, the neuroscience sub-study of 502 individuals from the MRC National Survey of Health and Development; the 1946 British birth cohort) was used to examine the cross-sectional relationships between these blood biomarkers, neuroimaging biomarkers (18F-florbetapir amyloid PET, whole brain and hippocampal volumes, white matter hyperintensity volume and cortical thickness in an AD signature region) and cognitive performance (PACC: preclinical Alzheimer’s composite and its constituents). Through a collaboration with the University of Gothenburg, a novel liquid chromatography-mass spectrometry (LC-MS) method for quantification of plasma amyloid-β species was compared with the commercial Simoa assays in Insight 46. This was the first direct method comparison study of plasma amyloid-β species for the detection of preclinical cerebral amyloid deposition. It showed that the LC-MS method, when combined with age, sex and APOE #-4 carrier status, was able to distinguish PET amyloid status with an optimal (Youden’s cut point) sensitivity of 85.7% and specificity of 72.7%. The Simoa biomarkers of plasma total tau and serum NFL were confirmed to be potentially useful prognostic markers, as lower AD signature cortical thickness was associated with higher plasma total tau and serum NFL, lower whole brain volume was associated with higher plasma total tau, and higher ventricular volume was associated with higher serum NFL. Lower PACC scores were associated with higher serum NFL and lower scores for a paired associative memory test in particular were associated with higher plasma total tau and serum NFL. Thirdly, through a collaboration with Harvard University and the University of California San Diego, a new N-terminal tau biomarker was developed in CSF and plasma that showed good accuracy in distinguishing individuals with symptomatic CSF-defined AD pathology from healthy controls. Taken together, this work has demonstrated the impact of pre-analytical factors on measurements of AD blood biomarkers, validated these biomarkers as indicators of the core pathologies of AD and helped to develop a new tau blood biomarker in AD

SHODHANA FROM THE PERSPECTIVE OF UTPATTI-STHANA OF VYADHI

According to Ayurvedic literature, there are three types of Doshas (Vata, Pitta, Kapha) in the body. These are present predominantly in certain places of the body and such places are known as Vishesha Sthana (Udbhvasthana) and the remaining are identified as Anya Sthana (general site). On the basis of three Dosha, Acharya classified Udbhvasthana into two, in which Pakwashaya is the Udbhvasthana for Vata. Adho Amashaya is the Udbhavasthana for Pitta and Urdhwa Amashaya is the Udbhavasthana for Kapha, and on the basis of these two Udbhava sthana Acharya classifies Shodhan into two in which Vamana is for Amasaya-Smuttha Vyadhi and Virechana for Pakvashya-Smuttha Vyadhi. This identification is done on the basis of physiological aspect of the body. The present article will explore the Shodhana aspects relating to the Udbhavasthana of Vyadhi as well as try to identify the therapeutic and prognostic significance of this understanding

Security Review and Study of DoS Attacks on LTE Mobile Network

The main objective of 3GPP long term evolution (LTE) is to provide a secure communication, high data rate and better communication for 4G users. LTE support all IP based data and voice with speed in order of hundreds of mega-bytes per second. Increase speed in accessing internet. Network to be attached by hackers using some attacks like spyware ,malware ,Denial-of-Service (DoS) and Distributed Denial-of-Service(DDoS) .This paper associated with security problem in LTE network and brief summary of DoS attack , DDoS attack and security vulnerabilities in LTE networks

Hyperspectral Image Classification

Hyperspectral image (HSI) classification is a phenomenal mechanism to analyze diversified land cover in remotely sensed hyperspectral images. In the field of remote sensing, HSI classification has been an established research topic, and herein, the inherent primary challenges are (i) curse of dimensionality and (ii) insufficient samples pool during training. Given a set of observations with known class labels, the basic goal of hyperspectral image classification is to assign a class label to each pixel. This chapter discusses the recent progress in the classification of HS images in the aspects of Kernel-based methods, supervised and unsupervised classifiers, classification based on sparse representation, and spectral-spatial classification. Further, the classification methods based on machine learning and the future directions are discussed

Violence Exposure and Self-esteem of School Going Adolescents in a Metropolitan City: A Preliminary Study

Background: Violence exposure in light of peer victimization and witnessing peer victimization is a common phenomenon in schools across the globe. The present study conceptualizes exposure at three personal levels: a) as a victim, b) as a witness, and c) as a perpetrator. Method & Materials: A semi-structured interview schedule and Rosenberg Self Esteem Scale were used as study tools. Results: The findings of the study show that the entire sample had experienced violence in one form or the other in school and had witnessed the same as well. Few of the adolescents had committed violence to take revenge and settle the score for being bullied. Victimization and witnessing violence in school triggered feelings like hurt, helplessness, sadness, and anger, whereas on committing violent acts feelings of joy, fun, content and satisfaction in adolescents. Twenty per cent of adolescents had low levels of self-esteem and 80% had average levels of self-esteem. The results showcase the reasons for bullying for fun, to hurt, to oppress or dominate others, due to personal grievances, jealousy, and growing less tolerance. Conclusion: Violence exposure to adolescents at school needs intervention. Keywords: Adolescents, violence exposure, bullying, self-estee

PHARMACEUTICAL DEVELOPMENT & ANTI-MICROBIAL STUDY (IN VITRO) OF TANKANAMRUTA MALAHAR W.S.R. TO RASA TARANGINI

“Tankan†which is among the Kshar traya mentioned in “Kshar trik vidnyaniya trayodasha taranaga†of Acharya Sadananda Sharma virachit Rasa tarangini. Tankan i.e., Borax (Na2B4O7 10H2O) is composed of boric acid & soda. It is a salt of tetra Boric acid, an important compound of Boron, which is also known as sodium biborate. Other Rasa Vaidyas also have included “Tankan†under the groups of Ksharatraya, Ksharapanchaka, Dravaka gana, Mitra panchaka etc. The present study was conducted to develop “Tankanamruta malahar†(pharmaceutically & to study its antimicrobial activity (In vitro). “Tankanamruta malahar†is a good combination of herbo-mineral preparation, which is indicated in Dushta vrana shodhan chikitsa or infected wounds. Though this formulation is from Ayurvedic classical text but there is a need to develop the standard procedure of preparation as they have faster & accurate results than oral administration of drug, so by the fusion of modern instruments & traditional methods of manufacturing procedures we have tried to make “Tankanamruta malahar†which contains Shuddha Tankan bhasma, Siktha taila, Sarji kshar, Shuddha pushpa kasis & Pipal twak kshar. Standardization describes all measures taken during manufacturing process like Shodhan, Maran, Kshar nirman & Siktha taila preparation etc & quality control leads to reproducible quality of particular product & in vitro study was performed to evaluate its anti-microbial activity against selected pathogens

Clinical Significance of Vamana and Virechana Karma in Kapha & Pitta Vyadhi: A Review

The most crucial aspect of Ayurveda treatments is Panchakarma that works to prevent and treat diseases. It also promotes and preserves general health, considered as worthful therapy due to its adequacy. This therapy involves five procedures which utilizes for various purposes. Virechana and Vamana Karma are important therapies of Panchakarma amongst the five therapeutic measures. These therapies mainly employed for the management of diseases of Kapha and Pitta vitiation. The drugs used for Virechana and Vamana Karma offers Tikshna, Sukshma and Ushna properties thus pacifies morbid Pitta, Kapha, and Vata doshas, also facilitate removal of toxins from the body. These two therapies utilize for managing many diseases under the heading of Shodhana Chikitsa. Present article reviewed the role of Virechana and Vamana Karma in Kapha and Pitta Vyadhi respectively

Wireless Power Transfer

It systems allow power to be transferred from one electrical network to another electrical network without need for wires or exposed contacts. There has been rapid expansion of WPT in mobile phone chargers and electric bulb and charging electric vehicles and dynamic charging electric vehicles, also called road powered electric vehicles. It is expected that WPT industry will grow  persistently in coming decaded, commonly wireless power transfers are conducted using an inductive coupling and followed by magnetic induction, we use magnetic induction using copper wire with a diameter. The wireless power transfer field would be in high demand for electric power to be supplied in the future

Sigmoid endometriosis in a post-menopausal woman leading to acute large bowel obstruction: A case report

AbstractIntroductionEndometriosis is usually a disease involving women of reproductive age. Colonic endometriosis is a rare sequelae. It usually presents vaguely with nonspecific abdominal pain, dyspareunia, fecal tenesmus, rectal bleeding or painful defecation. There are very few case reports of sigmoid endometriosis in the literature, more so ones involving post-menopausal women. Our report highlights such a case, mimicking a malignant rectosigmoid stricture leading to a large bowel obstruction.Case presentationA 63year old lady was referred by her General Practitioner for further investigation of recent altered bowel habit. She underwent an incomplete colonoscopy due to stricturing in the sigmoid. She subsequently was admitted with abdominal pain, distension and vomiting, with imaging consistent with a large bowel obstruction secondary to a stricturing mass within the rectosigmoid which was suspicious for malignancy. An emergency laparotomy and Hartmann’s procedure was performed. She had an uncomplicated post-surgical recovery. Histology revealed no underlying malignancy, but confirmed colonic endometriosis.ConclusionThis case report shows that colonic endometriosis, although rare, can be significantly infiltrative and lead to complications such as a large bowel obstruction. Diagnosing this condition can be challenging and usually requires histological confirmation

A diagnostic dilemma: Left-sided appendicitis in a 10 year old boy with previously undiagnosed intestinal malrotation. A case report

AbstractIntroductionIntestinal malrotation is a congenital rotational anomaly that occurs as a result of an arrest of normal rotation of the embryonic gut, said to occur in 1 in 6000 live births. Due to the abnormal caecal and appendix position, diagnosis of acute appendicitis becomes more challenging, thus leading to diagnostic and operative intervention delays. Our aim is to highlight the diagnostic challenges in this clinical scenario.Presentation of caseWe present a case of a 10 year old boy with previously undiagnosed intestinal malrotation with a left sided acute appendicitis. Initial symptoms lead to a treatment for gastroenteritis, however, due to ongoing pain a CT abdomen was done which showed the malrotation and appendicitis. He required a laparoscopy converted to open appendicectomy due to an appendicecal mass.DiscussionHistorically, intestinal malrotation was thought to be a disease of infancy with infrequent occurrence after the age of one year. However, recent analysis has shown an increase in presentations after one year of life into adulthood. Thus, the prevalence of malrotation in children and adults over the age of one year appear to be higher than initially presumed.ConclusionLeft sided acute appendicitis is a diagnostic dilemma, thus often leading to management delays. It is pertinent to remember that malrotation of the gut is more common than previously thought, and not just a disease of infancy. It is advisable to consider imaging studies while balancing the risk-benefit-ratio of radiation exposure, especially in paediatric cases to cinch the diagnosis