A clinical study of optic nerve involvement in patients with tuberculosis attending a tertiary health care center in North East

 Background: To screen for ocular finding of optic nerve involvement in patients with tuberculosis and documents these findings.Methods: The hospital based observational study was carried out in a tertiary care hospital in Assam  for  the duration of July 2018 to June 2019 in 384 diagnosed cases of tuberculosis patients who fulfil  the inclusion criteria during the study period.Results: 11 cases with optic nerve involvement was found out of 384 tuberculosis patients. Most common presenting complain was blurring of vision. Unilateral involvement was maximum. Most common finding was disc oedema.  Ocular TB cases was higher in extrapulmonary TB patients.Conclusions: Diagnosis of ocular Tb is mainly presumptive, based on history, clinical examination, adjunctive diagnostic tests and response to anti tuberculous therapy. Amongst 384 TB cases ocular manifestations were found in 11 cases and therefore, we can conclude that ocular manifestations hold significance in extra pulmonary manifestations of TB. So, TB patients need to have routine ocular examination for the early diagnosis and timely management

A clinical study of patients attending disability clinic in a tertiary care hospital of Assam, India

Background: The aim of the study was to determine the various types of congenital or acquired disorders causing permanent disability and their association with age, sex and visual acuity in patients attending disability clinic of department of ophthalmology, Jorhat medical college and hospital, Assam, from January 2018 to December 2018.Methods: A hospital-based cross-sectional study. 200 patients were enrolled in the duration of January 2018 to December 2018 and were analyzed for anomalies, etiology, sex and age at presentation.Results: Out of 200 cases analysed, 116 males and 84 females (Male: Female = 1.38:1) observed. The most common age group at presentation was 11-20 years (28.5%). 23% of cases were congenital. The most frequent ocular anomaly noted was microphthalmos (19%) followed by uveal coloboma (15%) and phthisis bulbi (14%).Conclusions: In a developing country like India, a large proportion of the childhood and adult blindness is avoidable. Action is needed to prevent blindness from vitamin A deficiency, measles, external ocular infections and chemical injuries. Specialist paediatric and optical services are required to manage cataract and glaucoma. Further work is indicated to elucidate the causes of anophthalmos, microphthalmos and coloboma. It would be useful to document the changing patterns in the causes of ocular disability to allow early action against emerging avoidable causes

Microwave assisted, BF3.OEt2 catalyzed efficient synthesis of tosylhydrazones and SC-XRD study of two of the synthesized tosylhydrazones

A highly efficient methodology for transformation of carbonyl compounds to their corresponding tosylhydrazones under microwave irradiation in presence of BF3.OEt2 catalyst has been developed and described here. The methodology is highly prospective for tosylhydrazone synthesis especially of diaryl ketones, as already existing procedures are found to be less effective for the same. Seventeen carbonyl compounds have been studied and found to deliver their corresponding products in excellent yield (92-98%). The products crystallize out from the reaction mixture during cooling at room temperature which excludes further purification processes. Single crystal X-ray diffraction (SC-XRD) analysis of two of the synthesized tosylhydrazones have been carried out and reported here.

Microwave assisted, BF3.OEt2 catalyzed efficient synthesis of tosylhydrazones and SC-XRD study of two of the synthesized tosylhydrazones

1579-1585A highly efficient methodology for transformation of carbonyl compounds to their corresponding tosylhydrazones under microwave irradiation in presence of BF3.OEt2 catalyst has been developed and described here. The methodology is highly prospective for tosylhydrazone synthesis especially of diaryl ketones, as already existing procedures are found to be less effective for the same. Seventeen carbonyl compounds have been studied and found to deliver their corresponding products in excellent yield (92-98%). The products crystallize out from the reaction mixture during cooling at room temperature which excludes further purification processes. Single crystal X-ray diffraction (SC-XRD) analysis of two of the synthesized tosylhydrazones have been carried out and reported here

On I-acceleration convergence of sequences of fuzzy real numbers

In this article we introduce the notion of ideal acceleration convergence of sequences of fuzzy real numbers. We have proved a decomposition theorem for ideal acceleration convergence of sequences as well as for subsequence transformations and studied different types of acceleration convergence of fuzzy real valued sequence

An \u3cem\u3ein Vitro\u3c/em\u3e Assessment of Liposomal Topotecan Simulating Metronomic Chemotherapy in Combination with Radiation in Tumor-Endothelial Spheroids

Low dose metronomic chemotherapy (LDMC) refers to prolonged administration of low dose chemotherapy designed to minimize toxicity and target the tumor endothelium, causing tumor growth inhibition. Topotecan (TPT) when administered at its maximum tolerated dose (MTD) is often associated with systemic hematological toxicities. Liposomal encapsulation of TPT enhances efficacy by shielding it from systemic clearance, allowing greater uptake and extended tissue exposure in tumors. Extended release of TPT from liposomal formulations also has the potential to mimic metronomic therapies with fewer treatments. Here we investigate potential toxicities of equivalent doses of free and actively loaded liposomal TPT (LTPT) and compare them to a fractionated low dose regimen of free TPT in tumor-endothelial spheroids (TES) with/without radiation exposure for a prolonged period of 10 days. Using confocal microscopy, TPT fluorescence was monitored to determine the accumulation of drug within TES. These studies showed TES, being more reflective of the in vivo tumor microenvironment, were more sensitive to LTPT in comparison to free TPT with radiation. More importantly, the response of TES to low-dose metronomic TPT with radiation was comparable to similar treatment with LTPT. This TES study suggests nanoparticle formulations designed for extended release of drug can simulate LDMC in vivo

Toxicity Evaluation of Magnetic Hyperthermia Induced by Remote Actuation of Magnetic Nanoparticles in 3D Micrometastasic Tumor Tissue Analogs for Triple Negative Breast Cancer

Magnetic hyperthermia as a treatment modality is acquiring increased recognition for loco-regional therapy of primary and metastatic lung malignancies by pulmonary delivery of magnetic nanoparticles (MNP). The unique characteristic of magnetic nanoparticles to induce localized hyperthermia in the presence of an alternating magnetic field (AMF) allows for preferential killing of cells at the tumor site. In this study we demonstrate the effect of hyperthermia induced by low and high dose of MNP under the influence of an AMF using 3D tumor tissue analogs (TTA) representing the micrometastatic, perfusion independent stage of triple negative breast cancer (TNBC) that infiltrates the lungs. While application of inhalable magnetic nanocomposite microparticles (MnMs) to the micrometastatic TNBC model comprised of TTA generated from cancer and stromal cells, showed no measureable adverse effects in the absence of AMF-exposure, magnetic hyperthermia generated under the influence of an AMF in TTA incubated in a high concentration of MNP (1 mg/ mL) caused significant increase in cellular death/ damage with mechanical disintegration and release of cell debris indicating the potential of these inhalable composites as a promising approach for thermal treatment of diseased lungs. The novelty and significance of this study lies in the development of methods to evaluate in vitro the application of inhalable composites containing MNPs in thermal therapy using a physiologically relevant metastatic TNBC model representative of the microenvironmental characteristics in secondary lung malignancies

3D tumor tissue analogs and their orthotopic implants for understanding tumor-targeting of microenvironment-responsive nanosized chemotherapy and radiation

AbstractAn appropriate representation of the tumor microenvironment in tumor models can have a pronounced impact on directing combinatorial treatment strategies and cancer nanotherapeutics. The present study develops a novel 3D co-culture spheroid model (3D TNBC) incorporating tumor cells, endothelial cells and fibroblasts as color-coded murine tumor tissue analogs (TTA) to better represent the tumor milieu of triple negative breast cancer in vitro. Implantation of TTA orthotopically in nude mice, resulted in enhanced growth and aggressive metastasis to ectopic sites. Subsequently, the utility of the model is demonstrated for preferential targeting of irradiated tumor endothelial cells via radiation-induced stromal enrichment of galectin-1 using anginex conjugated nanoparticles (nanobins) carrying arsenic trioxide and cisplatin. Demonstration of a multimodal nanotherapeutic system and inclusion of the biological response to radiation using an in vitro/in vivo tumor model incorporating characteristics of tumor microenvironment presents an advance in preclinical evaluation of existing and novel cancer nanotherapies.From the Clinical EditorExisting in-vivo tumor models are established by implanting tumor cells into nude mice. Here, the authors described their approach 3D spheres containing tumor cells, enodothelial cells and fibroblasts. This would mimic tumor micro-environment more realistically. This interesting 3D model should reflect more accurately tumor response to various drugs and would enable the design of new treatment modalities

Radiation-Enhanced Therapeutic Targeting of Galectin-1 Enriched Malignant Stroma in Triple Negative Breast Cancer

Currently there are no FDA approved targeted therapies for Triple Negative Breast Cancer (TNBC). Ongoing clinical trials for TNBC have focused primarily on targeting the epithelial cancer cells. However, targeted delivery of cytotoxic payloads to the non-transformed tumor associated-endothelium can prove to be an alternate approach that is currently unexplored. The present study is supported by recent findings on elevated expression of stromal galectin-1 in clinical samples of TNBC and our ongoing findings on stromal targeting of radiation induced galectin-1 by the anginex-conjugated arsenic-cisplatin loaded liposomes using a novel murine tumor model. We demonstrate inhibition of tumor growth and metastasis in response to the multimodal nanotherapeutic strategy using a TNBC model with orthotopic tumors originating from 3D tumor tissue analogs (TTA) comprised of tumor cells, endothelial cells and fibroblasts. The ‘rigorous’ combined treatment regimen of radiation and targeted liposomes is also shown to be well tolerated. More importantly, the results presented provide a means to exploit clinically relevant radiation dose for concurrent receptor mediated enhanced delivery of chemotherapy while limiting overall toxicity. The proposed study is significant as it falls in line with developing combinatorial therapeutic approaches for stroma-directed tumor targeting using tumor models that have an appropriate representation of the TNBC microenvironment

Abnormal cognition, sleep, eeg and brain metabolism in a novel knock-in alzheimer mouse, plb1

Late-stage neuropathological hallmarks of Alzheimer's disease (AD) are β-amyloid (βA) and hyperphosphorylated tau peptides, aggregated into plaques and tangles, respectively. Corresponding phenotypes have been mimicked in existing transgenic mice, however, the translational value of aggressive over-expression has recently been questioned. As controlled gene expression may offer animal models with better predictive validity, we set out to design a transgenic mouse model that circumvents complications arising from pronuclear injection and massive over-expression, by targeted insertion of human mutated amyloid and tau transgenes, under the forebrain- and neurone-specific CaMKIIα promoter, termed PLB1 Double. Crossing with an existing presenilin 1 line resulted in PLB1 Triple mice. PLB1 Triple mice presented with stable gene expression and age-related pathology of intra-neuronal amyloid and hyperphosphorylated tau in hippocampus and cortex from 6 months onwards. At this early stage, pre-clinical 18FDG PET/CT imaging revealed cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain. Quantitative EEG analyses yielded heightened delta power during wakefulness and REM sleep, and time in wakefulness was already reliably enhanced at 6 months of age. These anomalies were paralleled by impairments in long-term and short-term hippocampal plasticity and preceded cognitive deficits in recognition memory, spatial learning, and sleep fragmentation all emerging at ~12 months. These data suggest that prodromal AD phenotypes can be successfully modelled in transgenic mice devoid of fibrillary plaque or tangle development. PLB1 Triple mice progress from a mild (MCI-like) state to a more comprehensive AD-relevant phenotype, which are accessible using translational tools such as wireless EEG and microPET/CT.</p