A Review on a Deep Learning Perspective in Brain Cancer Classification.

A World Health Organization (WHO) Feb 2018 report has recently shown that mortality rate due to brain or central nervous system (CNS) cancer is the highest in the Asian continent. It is of critical importance that cancer be detected earlier so that many of these lives can be saved. Cancer grading is an important aspect for targeted therapy. As cancer diagnosis is highly invasive, time consuming and expensive, there is an immediate requirement to develop a non-invasive, cost-effective and efficient tools for brain cancer characterization and grade estimation. Brain scans using magnetic resonance imaging (MRI), computed tomography (CT), as well as other imaging modalities, are fast and safer methods for tumor detection. In this paper, we tried to summarize the pathophysiology of brain cancer, imaging modalities of brain cancer and automatic computer assisted methods for brain cancer characterization in a machine and deep learning paradigm. Another objective of this paper is to find the current issues in existing engineering methods and also project a future paradigm. Further, we have highlighted the relationship between brain cancer and other brain disorders like stroke, Alzheimer's, Parkinson's, and Wilson's disease, leukoriaosis, and other neurological disorders in the context of machine learning and the deep learning paradigm.

Developing an in vitro screening assay platform for evaluation of antifibrotic drugs using precision-cut liver slices.

BACKGROUND: Precision-cut liver slices present different cell types of liver in a physiological context, and they have been explored as effective in vitro model systems to study liver fibrosis. Inducing fibrosis in the liver slices using toxicants like carbon tetrachloride is of less relevance to human disease conditions. Our aim for this study was to establish physiologically relevant conditions in vitro to induce fibrotic phenotypes in the liver slices. RESULTS: Precision-cut liver slices of 150 µm thickness were obtained from female C57BL/6 J mice. The slices were cultured for 24 hours in media containing a cocktail of 10 nM each of TGF-ß, PDGF, 5 µM each of lysophosphatidic acid and sphingosine 1 phosphate and 0.2 µg/ml of lipopolysaccharide along with 500 µM of palmitate and were analyzed for triglyceride accumulation, stress and inflammation, myofibroblast activation and extracellular matrix (ECM) accumulation. Incubation with the cocktail resulted in increased triglyceride accumulation, a hallmark of steatosis. The levels of Acta2, a hallmark of myofibroblast activation and the levels of inflammatory genes (IL-6, TNF-α and C-reactive protein) were significantly elevated. In addition, this treatment resulted in increased levels of ECM markers - collagen, lumican and fibronectin. CONCLUSIONS: This study reports the experimental conditions required to induce fibrosis associated with steatohepatitis using physiologically relevant inducers. The system presented here captures various aspects of the fibrosis process like steatosis, inflammation, stellate cell activation and ECM accumulation and serves as a platform to study the liver fibrosis in vitro and to screen small molecules for their antifibrotic activity.

Nonconvulsive status epilepticus and Creutzfeldt-Jakob-like EEG changes in a case of lithium toxicity.

We report a case of a 63-year-old lady with bipolar affective disorder on lithium who was brought to our emergency center in a comatose state. Neurologically, the patient was comatose and had generalized hypotonia and hyporeflexia. Lithium toxicity was considered. Laboratory examinations revealed leukocytosis, normal blood sugar, blood level of lithium was 4.7 mEq/L and she had renal dysfunction. Cerebrospinal fluid examination and cranial computerized tomography were unremarkable. Blood lithium level was 4.7 mEq/L. Hemodialysis was initiated. However, in spite of dialysis and decreasing lithium levels, the patient remained unconscious. A possibility of nonconvulsive status epilepticus was considered; hence, EEG was advised. The EEG demonstrated bihemispheric slowing (4- to 5-Hz theta range) with bilateral periodic triphasic waves of 1- to 2-Hz frequency, similar to the EEG changes seen in Creutzfeldt-Jakob disease. She was started on lorazepam. Her sensorium improved gradually, which correlated with the decline in blood lithium levels. A normal background alpha rhythm on EEG was ensured prior to discharge. At discharge, clinically, she had recovered completely, with no apparent neurological deficit or cognitive impairment. This case highlights the importance of therapeutic drug-level monitoring of lithium, especially where toxicity is suspected, and the important role electroencephalography plays in diagnosing NCSE and its management.

Facial phenotype at different ages and cardiovascular malformations in children with Williams-Beuren syndrome: a study from India.

Williams-Beuren syndrome (WBS) is one of the microdeletion syndromes associated with distinct facial features, characteristic behavior phenotype (overfriendly behavior), congenital heart disease, and other malformations. Clinical features in WBS are age dependent. It is important to be aware of variable age dependent phenotype, especially facial phenotype due to its crucial role in diagnosis. Here we describe the facial phenotype of WBS at different ages (3 months to 15.1 years) and congenital heart malformations in 27 patients FISH positive for 7q11.23 microdeletion.

Arthemeter-loaded lipid nanoparticles produced by modified thin-film hydration: Pharmacokinetics, toxicological and in vivo anti-malarial activity.

Artemether-loaded lipid nanoparticles (ARM-LNP) composed of 5% (w/v) lipid mass were produced by a modified thin-film hydration method using glyceryl trimyristate (solid lipid) and soybean oil (as liquid lipid in a concentration ranging from 0 to 45% (w/v) with respect to the total lipid mass). The particles were loaded with 10% of the anti-malarial ARM and surface-tailored with a combination of non-ionic, cationic or anionic surfactants. ARM-LNP were further characterized for their mean particle size, zeta potential and encapsulation efficiency, reporting optimized values below 120nm (PI<0.250), -38mV and 97% (w/w), respectively. ARM-LNP composed of 45% soybean oil depicted a spherical-like shape by transmission electron microscopy and a biphasic release profile in phosphate buffer. Haemolytic activity was within the acceptable range (7%) revealing low toxicity risk of LNP for parenteral delivery of ARM. Biocompatibility was confirmed by hepato- and nephrotoxicity analyses. Histopathological analysis showed no significant histological changes in liver and kidney tissues in adult Swiss Albino mice treated with the selected formulations. In vivo anti-malarial activity of ARM was enhanced when formulated as LNP, in comparison to a conventional plain drug solution and to a marketed formulation which are currently in use to treat malaria patients.

Preparation and evaluation of nimesulide-loaded ethylcellulose and methylcellulose nanoparticles and microparticles for oral delivery.

The present study was designed to assess and compare with a range of surfactant-coated, nimesulide-free, and nimesulide-loaded ethylcellulose/methylcellulose (EC/MC) nanoparticles that were prepared by varying drug concentration (ED/MD), polymer concentration (EP/MP), and surfactant concentration (ES/MS). EC/MC nanoparticles prepared by desolvation method produced discrete particles and they were characterized by SEM, AFM, and FTIR studies. The particles mean size diameter (nm) ranged from 244 to 1056 nm and 1065 to 1710 nm for EC and MC nanoparticles, respectively. Studies on drug: polymer ratio showed a linear relationship between drug concentration and percentage of loading in nanoparticles. The encapsulation efficiency decreased with the increase of nimesulide concentration with respect to polymer concentration. Encapsulation efficiency of drug-loaded nanoparticles was varied between 32.8% and 64.9%. The in vitro release of drug-loaded nanoparticles was found to be a first order. This was significantly increased in EC nanoparticles (95.50%) in comparison with MC nanoparticles (95.12%) after 12 h in 24 h long study. Nimesulide release from EC nanoparticles was much slower at slightly alkaline pH 7.4. The in vitro hemolysis tests of nanoparticles were carried out to ascertain the hemocompatibility and shown to be insignificant for EC nanoparticles. In comparison, ES4 from EC formulations with nimesulide was found to be promising with slow and sustained drug release.

1-O-alkylglycerol stabilized carbamazepine intravenous o/w nanoemulsions for drug targeting in mice.

Carbamazepine (CBZ) is used in the treatment of generalized tonic clonic and partial seizures. In seizure disorder the focal point of treatment is brain. At present no commercial parenteral formulation of CBZ is available. We developed o/w nanoemulsions of CBZ stabilized by 1-O-alkylglycerol/lecithin for intravenous administration and evaluated the brain targeting potential of these formulations. The nanoemulsions were characterized for globule size, zeta potential (ZP), CBZ content and in vivo tissue distribution in mice. The in vivo data revealed a significant uptake of CBZ in all tissues. Among the nanoemulsions, 1-O-decylglycerol stabilized system showed significantly higher tissue levels and availability of CBZ. Particularly for this system 2.37 times higher brain availability and a brain/serum concentration ratio of 3.0 at 30 min is an important finding. This indicates the brain targeting potential. A systematic formulation development of CBZ nanoemulsions employing 1-O-alkylglycerols might pave way to achieve selective brain delivery of this important antiepileptic drug.

Chronic postoperative wound infection caused by Myocobacterium fortuitum complex.

Mycobacterium fortuitum in a rapidly growing atypical mycobacteia, sometimes associated with nosocomial infections in human. These infections are often difficult to identify; and treat even after indentification. We report here a case of chronic post operative wound infection due to M. fortuitum.