CT cisternography in cerebrospinal fluid rhinorrhea: Could it have a therapeutic role?

Two cases of spontaneous cessation of cerebrospinal fluid (CSF) rhinorrhea following iohexol computerized tomographic (CT) cisternography are presented. This report contradicts the current thinking about conservative treatment in CSF rhinorrhea. We propose that iohexol CT cisternography may have a therapeutic role in the management of spontaneous CSF rhinorrhea.     

Statin-induced necrotizing autoimmune myopathy: a systematic review

Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing autoimmune myopathy in some patients. We reviewed case reports of 80 patients from 2010 to present diagnosed with statin-induced necrotizing autoimmune myopathy (SINAM), aiming to analyze the clinical, physiological, serologic characteristics and outcomes of SINAM. The mean age of these patients was 66 ±9.4, the majority being male (61.3%). All patients reported proximal muscle weakness, and a few had myalgias, extra muscular symptoms such as dysphagia, and pulmonary complications. Most of the patients were on atorvastatin, simvastatin, or rosuvastatin. The mean creatine kinase was 10,094.2 ±7,351.7 U/l, and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme was positive for 93.8% of patients. The majority of patients were started on steroids; other treatments were also used. Prompt cessation of statins and initiation of immunosuppressants reduced morbidity and mortality.     

Antiproliferative activity and standardization of Tecomella undulata bark extract on K562 cells

Ethnopharmacological relevance

The bark of Tecomella undulata is primarily used in the treatment of syphilis, painful swellings and cancer by traditional healers. Also, it is claimed to be useful in treating urinary discharges, enlargement of spleen, leucorrhoea, leukoderma, tumors, liver disorders, gonorrhea, gout and promotes wound healing in Indian traditional system of medicine.

Aim

To establish a scientific validation for the antitumor effects of Tecomella undulata bark and explore the mechanistic pathway in chronic myeloid leukemia cell line, K562. The study was further extended to standardize the extract using quercetin as biomarker.

Methods

Induction of apoptosis by chloroform extract of Tecomella undulata bark (CTUB) was determined by MTT, Annexin V and caspase activation assays. The cell cycle analysis was done by flow cytometer and nuclear staining by DAPI. The standardization of the extract was performed through reverse phase-HPLC method under PDA detection.

Result

Results clearly showed the induction of apoptosis by CTUB in K562 cells. The effect was found to be dose dependent, having IC₅₀ of 30 μg/ml with activation of FAS, FADD, caspase 8, caspase 3/7 and fragmentation of DNA. The bioactive CTUB was determined to possess 0.03% (w/w) of quercetin.

Conclusion

The investigation clearly demonstrated the potential antitumor effect of CTUB, thereby validating the traditional claim. Quercetin, known to have anticancer activity is being reported and quantified for the first time from the bark of Tecomella undulata.     

Bone age determination using only the index finger: a novel approach using a convolutional neural network compared with human radiologists

Background

Recently developed convolutional neural network (CNN) models determine bone age more accurately than radiologists.

Objective

The purpose of this study was to determine whether a CNN and radiologists can accurately predict bone age from radiographs using only the index finger rather than the whole hand.

Materials and methods

We used a public anonymized dataset provided by the Radiological Society of North America (RSNA) pediatric bone age challenge. The dataset contains 12,611 hand radiographs for training and 200 radiographs for testing. The index finger was cropped from these images to create a second dataset. Separate CNN models were trained using the whole-hand radiographs and the cropped second-digit dataset using the consensus ground truth provided by the RSNA bone age challenge. Bone age determination using both models was compared with ground truth as provided by the RSNA dataset. Separately, three pediatric radiologists determined bone age from the whole-hand and index-finger radiographs, and the consensus was compared to the ground truth and CNN-model-determined bone ages.

Results

The mean absolute difference between the ground truth and CNN bone age for whole-hand and index-finger was similar (4.7 months vs. 5.1 months, P=0.14), and both values were significantly smaller than that for radiologist bone age determination from the single-finger radiographs (8.0 months, P<0.0001).

Conclusion

CNN-model-determined bone ages from index-finger radiographs are similar to whole-hand bone age interpreted by radiologists in the dataset, as well as a model trained on the whole-hand radiograph. In addition, the index-finger model performed better than the ground truth compared to subspecialty trained pediatric radiologists also using only the index finger to determine bone age. The radiologist interpreting bone age can use the second digit as a reliable starting point in their search pattern.

     

Cytogenetic effects of trifluoperazine in mice

The cytogenetic effects of trifluoperazine have been studied in male Swiss albino mice using the micronucleus test, chromosomal analysis in germ cells and a sperm morphology assay. The mice were treated by gavage with 80, 120 or 160 micrograms trifluoperazine/kg, divided in each case into two equal doses given 24 hr apart. The dose levels were selected on the basis of standard human therapeutic dosage. Compared with the findings in control mice dosed with distilled water, there were significant increases in the frequency of micronuclei, of chromosomal aberrations in the spermatocytes and of abnormal sperms, at all the levels of trifluoperazine treatment.     

Thermodynamic Modeling Study of Carbonation of Portland Cement

The assessment of the extent of carbonation and related phase changes is important for the evaluation of the durability aspects of concrete. The phase assemblage of Portland cements with different clinker compositions is evaluated using thermodynamic calculations. Four different compositions of cements, as specified by ASTM cements types I to IV, are considered in this study. Calcite, zeolites, and gypsum were identified as carbonation products. CO₂ content required for full carbonation had a direct relationship with the initial volume of phases. The CO₂ required for portlandite determined the initiation of carbonation of C-S-H. A continual decrease in the pH of pore solution and a decrease in Ca/Si is observed with the carbonation of C-S-H. Type II cement exhibited rapid carbonation at relatively less CO₂for full carbonation, while type III required more CO₂ to carbonate to the same level as other types of cement. The modeling of carbonation of different Portland cements provided insights into the quantity of CO₂ required to destabilize different hydrated products into respective carbonated phases.     

Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment

The goals of our investigations are to develop and characterize self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10 (CoQ10), using polyglycolyzed glycerides (PGG) as emulsifiers and to evaluate their bioavailability in dogs. Solubility of CoQ10 was determined in various oils and surfactants. SEDDS consisted of oil, a surfactant and a cosurfactant. Four types of self-emulsifying formulations were prepared using two oils (Myvacet 9-45 and Captex-200), two emulsifiers (Labrafac CM-10 and Labrasol) and a cosurfactant (lauroglycol). In all the formulations, the level of CoQ10 was fixed at 5.66% w/w of the vehicle. The in vitro self-emulsification properties and droplet size analysis of these formulations upon their addition to water under mild agitation conditions were studied. Pseudo-ternary phase diagrams were constructed identifying the efficient self-emulsification region. From these studies, an optimized formulation was selected and its bioavailability was compared with a powder formulation in dogs. Medium chain oils and Myvacet 9-45 provided higher solubility than long chain oils. Efficient and better self-emulsification processes were observed for the systems containing Labrafac CM-10 than formulations containing Labrasol. Addition of a cosurfactant improved the spontaneity of self-emulsification. From these studies, an optimized formulation consisting of Myvacet 9-45 (40%), Labrasol (50%) and lauroglycol (10%) was selected for its bioavailability assessment. A two-fold increase in the bioavailability was observed for the self-emulsifying system compared to a powder formulation. SEDDS have improved the bioavailability of CoQ10 significantly. The data suggest the potential use of SEDDS to provide an efficient way of improving oral absorption of lipophilic drugs.     

Intravenous injection of oncolytic picornavirus SVV-001 prolongs animal survival in a panel of primary tumor–based orthotopic xenograft mouse models of pediatric glioma

Background

Seneca Valley virus (SVV-001) is a nonpathogenic oncolytic virus that can be systemically administered and can pass through the blood–brain barrier. We examined its therapeutic efficacy and the mechanism of tumor cell infection in pediatric malignant gliomas.

Methods

In vitro antitumor activities were examined in primary cultures, preformed neurospheres, and self-renewing glioma cells derived from 6 patient tumor orthotopic xenograft mouse models (1 anaplastic astrocytoma and 5 GBM). In vivo therapeutic efficacy was examined by systemic treatment of preformed xenografts in 3 permissive and 2 resistant models. The functional role of sialic acid in mediating SVV-001 infection was investigated using neuraminidase and lectins that cleave or competitively bind to linkage-specific sialic acids.

Results

SVV-001 at a multiplicity of infection of 0.5 to 25 replicated in and effectively killed primary cultures, preformed neurospheres, and self-renewing stemlike single glioma cells derived from 4 of the 6 glioma models in vitro. A single i.v. injection of SVV-001 (5 × 10¹² viral particles/kg) led to the infection of orthotopic xenografts without harming normal mouse brain cells, resulting in significantly prolonged survival in all 3 permissive and 1 resistant mouse models (P < .05). Treatment with neuraminidase and competitive binding using lectins specific for α2,3-linked and/or α2,6-linked sialic acid significantly suppressed SVV-001 infectivity (P < .01).

Conclusion

SVV-001 possesses strong antitumor activity against pediatric malignant gliomas and utilizes α2,3-linked and α2,6-linked sialic acids as mediators of tumor cell infection. Our findings support the consideration of SVV-001 for clinical trials in children with malignant glioma.