Post-treatment imaging of gliomas: challenging the existing dogmas.

Gliomas are the commonest malignant central nervous system tumours in adults and imaging is the cornerstone of diagnosis, treatment, and post-treatment follow-up of these patients. With the ever-evolving treatment strategies post-treatment imaging and interpretation in glioma remains challenging, more so with the advent of anti-angiogenic drugs and immunotherapy, which can significantly alter the appearance in this setting, thus making interpretation of routine imaging findings such as contrast enhancement, oedema, and mass effect difficult to interpret. This review details the various methods of management of glioma including the upcoming novel therapies and their impact on imaging findings, with a comprehensive description of the imaging findings in conventional and advanced imaging techniques. A systematic appraisal for the existing and emerging techniques of imaging in these settings and their clinical application including various response assessment guidelines and artificial intelligence based response assessment will also be discussed.

Ion specific tuning of nanoparticle dispersion in an ionic liquid: a structural, thermoelectric and thermo-diffusive investigation.

Dispersions of charged maghemite nanoparticles (NPs) in EAN (ethylammonium nitrate) a reference Ionic Liquid (IL) are studied here using a number of static and dynamical experimental techniques; small angle scattering (SAS) of X-rays and of neutrons, dynamical light scattering and forced Rayleigh scattering. Particular insight is provided regarding the importance of tuning the ionic species present at the NP/IL interface. In this work we compare the effect of Li+, Na+ or Rb+ ions. Here, the nature of these species has a clear influence on the short-range spatial organisation of the ions at the interface and thus on the colloidal stability of the dispersions, governing both the NP/NP and NP/IL interactions, which are both evaluated here. The overall NP/NP interaction is either attractive or repulsive. It is characterised by determining, thanks to the SAS techniques, the second virial coefficient A2, which is found to be independent of temperature. The NP/IL interaction is featured by the dynamical effective charge ξeff0 of the NPs and by their entropy of transfer SNP (or equivalently their heat of transport ) determined here thanks to thermoelectric and thermodiffusive measurements. For repulsive systems, an activated process rules the temperature dependence of these two latter quantities.

Imaging of Neck Nodes in Head and Neck Cancers - a Comprehensive Update.

Cervical lymph node metastases from head and neck squamous cell cancers significantly reduce disease-free survival and worsen overall prognosis and, hence, deserve more aggressive management and follow-up. As per the eighth edition of the American Joint Committee on Cancer staging manual, extranodal extension, especially in human papillomavirus-negative cancers, has been incorporated in staging as it is important in deciding management and significantly impacts the outcome of head and neck squamous cell cancer. Lymph node imaging with various radiological modalities, including ultrasound, computed tomography and magnetic resonance imaging, has been widely used, not only to demonstrate nodal involvement but also for guided histopathological evaluation and therapeutic intervention. Computed tomography and magnetic resonance imaging, together with positron emission tomography, are used widely for the follow-up of treated patients. Finally, there is an emerging role for artificial intelligence in neck node imaging that has shown promising results, increasing the accuracy of detection of nodal involvement, especially normal-appearing nodes. The aim of this review is to provide a comprehensive overview of the diagnosis and management of involved neck nodes with a focus on sentinel node anatomy, pathogenesis, imaging correlates (including radiogenomics and artificial intelligence) and the role of image-guided interventions.

Glioma radiogenomics and artificial intelligence: road to precision cancer medicine.

Radiogenomics refers to the study of the relationship between imaging phenotypes and gene expression patterns/molecular characteristics, which might allow improved diagnosis, decision-making, and predicting patient outcomes in the context of multiple diseases. Central nervous system (CNS) tumours contribute to significant cancer-related mortality in the present age. Although historically CNS neoplasms were classified and graded based on microscopic appearance, there was discordance between two histologically similar tumours that showed varying prognosis and behaviour, attributable to their molecular signatures. These led to the incorporation of molecular markers in the classification of CNS neoplasms. Meanwhile, advancements in imaging technology such as diffusion-based imaging (including tractography), perfusion, and spectroscopy in addition to the conventional imaging of glial neoplasms, have opened an avenue for radiogenomics. This review touches upon the schema of the current classification of gliomas, concepts behind molecular markers, and parameters that are used in radiogenomics to characterise gliomas and the role of artificial intelligence for the same. Further, the role of radiomics in the grading of brain tumours, prediction of treatment response and prognosis has been discussed. Use of automated and semi-automated tumour segmentation for radiotherapy planning and follow-up has also been discussed briefly.

Fracture Diodes: Directional Asymmetry of Fracture Toughness.

Toughness describes the ability of a material to resist fracture or crack propagation. It is demonstrated here that fracture toughness of a material can be asymmetric, i.e., the resistance of a medium to a crack propagating from right to left can be significantly different from that to a crack propagating from left to right. Such asymmetry is unknown in natural materials, but we show that it can be built into artificial materials through the proper control of microstructure. This paves the way for control of crack paths and direction, where fracture-when unavoidable-can be guided through predesigned paths to minimize loss of critical components.

First Measurement of Inclusive Muon Neutrino Charged Current Differential Cross Sections on Argon at E_{ν}∼0.8 GeV with the MicroBooNE Detector.

We report the first measurement of the double-differential and total muon neutrino charged current inclusive cross sections on argon at a mean neutrino energy of 0.8 GeV. Data were collected using the MicroBooNE liquid argon time projection chamber located in the Fermilab Booster neutrino beam and correspond to 1.6×10^{20} protons on target of exposure. The measured differential cross sections are presented as a function of muon momentum, using multiple Coulomb scattering as a momentum measurement technique, and the muon angle with respect to the beam direction. We compare the measured cross sections to multiple neutrino event generators and find better agreement with those containing more complete treatment of quasielastic scattering processes at low Q^{2}. The total flux integrated cross section is measured to be 0.693±0.010(stat)±0.165(syst)×10^{-38} cm^{2}.

Effectiveness of Early Hematopoietic Stem Cell Transplantation in Preventing Neurocognitive Decline in Mucopolysaccharidosis Type II: A Case Series.

The early progressive form of the X-linked disorder, Hunter syndrome or mucopolysaccharidosis type II (MPS II) (OMIM #309900), is characterized by cognitive decline, and pulmonary and cardiac complications that often cause death before 20 years of age. Deficiency of the lysosomal enzyme, iduronate-2-sulfatase (EC 3.1.6.13) results in deposition of the glycosaminoglycans, dermatan, and heparan sulfate in various tissues. In recent years, enzyme replacement therapy (ERT) has become the mainstay of treatment, but is expensive and ineffective in arresting cognitive decline. Hematopoietic stem cell transplantation (HSCT) also provides enzyme replacement, and may be effective in stabilizing neurocognitive function if initiated early, though data are limited. We present a case series of four patients who demonstrated neurocognitive stabilization with early HSCT. HSCT is a potentially underutilized treatment strategy for select groups of MPS II patients.

Quantitative birefringence microscopy with collinearly propagating orthogonally polarized beams.

Full-field evaluation of spatially varying birefringence is realized by allowing two mutually orthogonally polarized collinearly propagating laser beams to be incident on a birefringent sample. This is achieved by use of a modified Sagnac interferometer. A half-wave plate is placed in the exit path of the interferometer to adjust the polarizations of the incident beams as required. Amplitude components of the light emerging from the birefringent object are then selected and/or combined by a polarizer, and intensities for required orientation of the half-wave plate and the analyzer are digitally recorded. It is shown that a maximum of four frames of intensity data is sufficient for complete evaluation of birefringence. The proposed technique is aimed towards birefringence measurements in microscopic biological specimens where the magnitude of retardation lies in the range of 0-π radians. Simulated and experimental results are presented.

Refractive index profilometry using the total internally reflected light field.

A full-field polarization-based technique is presented for quantitative evaluation of the spatial distribution of the refractive index in macro and micro samples. The sample is mounted on a glass-air interface of a prism, illuminated by a linearly polarized collimated light beam, and two intensity frames are digitally recorded with specific orientations of an analyzer. The pair of intensity data frames captured with this simple setup is combined through an algorithm specially developed for the purpose, to yield the phase difference between the transverse electric and transverse magnetic components of the total internally reflected light field. The phase difference is then related to the refractive index of the sample. Experimental results for refractive index variations in a laser-etched glass plate and red blood corpuscles are presented. One of the salient features of the proposed technique is that the depth of measurement is dependent on the penetration depth of the sample's evanescent field, which is typically of the order of a few hundred nanometers, thereby facilitating refractive index measurements along a thin section of the sample.

Safe limit of arsenic in soil in relation to dietary exposure of arsenicosis patients from Malda district, West Bengal- A case study.

Safe limit of arsenic in soil in relation to dietary exposure of arsenicosis patients was established in Malda district of West Bengal. Out of 182 participants examined, 80 (43.9%) participants showed clinical features of arsenicosis, characterized by arsenical skin lesion (pigmentation and keratosis), while 102 participants did not have any such lesion (control). Experimental results of the twenty eight soils (own field) of the participants showed the mean Olsen extractable and total arsenic concentration of 0.206 and 6.70mgkg-1, respectively. Arsenic concentration in rice grain ranged from 2.00 to 1260µgkg-1 with the mean value of 146µgkg-1. The hazard quotient (HQ) for intake of As by human through consumption of rice varied from 0.03 to 3.52. HQ exceeds 1.0 for drinking water and rice grain grown in the study area in many cases. As high as 77.6% variation in As content in rice grain could be explained by the solubility-free ion activity model. Toxic limit of extractable As in soil for rice in relation to soil properties and human health hazard, associated with consumption of rice grain by human, was established. For example, the permissible limit of Olsen extractable As in soil would be 0.43mgkg-1 for rice cultivation, if soil pH and organic carbon content were 7.5% and 0.50%, respectively. However, the critical limit of Olsen extractable As in soil would be 0.54mgkg-1, if soil pH and organic carbon were 8.5% and 0.75%, respectively. The conceptual framework of fixing the toxic limit of arsenic in soils with respect to soil properties and human health under modeling-framework was established.

Low-level birefringence measurement by cyclic-path polarization interferometer.

A modified cyclic-path interferometer is employed for complete measurement of spatially varying birefringence. An expanded and collimated laser beam intercepted by a birefringent specimen is incident on a polarization-masked cube beam splitter, resulting in two mutually orthogonal polarization components propagating along clockwise and counterclockwise directions in the interferometer. These two wavefronts are made to interfere for four specific orientations of an analyzer. Suitable combinations of the interferograms result in determination of the direction of birefringence and its magnitude. Experimental results are presented.

PTEN negatively regulates mTORC2 formation and signaling in grade IV glioma via Rictor hyperphosphorylation at Thr1135 and direct the mode of action of an mTORC1/2 inhibitor.

To investigate the role of PTEN (phosphatase and tensin homolog) in mammalian target of rapamycin complex 2 (mTORC2) signaling in glioblastoma multiforme (GBM), we found higher activation of mTORC2 in PTEN(mu) cells, as evidenced by enhanced phosphorylation of mTOR (Ser2481), AKT (Ser473) and glycogen synthase kinase 3 beta (GSK3ß) (Ser9) as compared with PTEN(wt) cells. In addition, PTEN(wt) cells upon PTEN depletion showed mTORC2 activation. The reduced mTORC2 signaling in PTEN(wt) cells was related to higher Rictor phosphorylation at Thr1135 residue. Phosphorylation of Rictor at Thr1135 inhibited its association with mTORC and thus there was a reduction in mTORC2 complex formation. In addition, PTEN(wt) cells expressing mutated Rictor in which Thr1135 was substituted with alanine, showed enhanced mTORC2 formation and signaling. This enhanced mTORC2 signaling promoted inactivation of GSK3ß. Thus, we established the reciprocal activation of mTORC2 and GSK3ß in GBM. To the best of our knowledge, this is the first report describing role of PTEN in mTORC2 formation by promoting Rictor phosphorylation (Thr1135) in GBM. Furthermore, the drug sensitivity of mTORC2 was evaluated. A newly identified carbazole alkaloid, mahanine, showed cytotoxicity in both PTEN(mu) and PTEN(wt) cells. It inhibited both mTORC1/2 and AKT completely in PTEN(mu) cells, whereas it inhibited only mTORC1 in PTEN(wt) cells. Cytotoxity and AKT-inhibitory activity of the mTORC1/2 inhibitor was increased either by depleting PTEN or in combination with phosphatidylinositol 3 kinase inhibitors in PTEN(wt) cells. In contrast, depletion of Rictor decreased the cytotoxicity of the mTORC1/2 inhibitor in PTEN(mu) cells. Thus, PTEN has an important role in mTORC2 formation and also influences the effectiveness of an mTORC1/2 inhibitor in GBM.

Identification of different species of Bacillus isolated from Nisargruna Biogas Plant by FTIR, UV-Vis and NIR spectroscopy.

Definitive identification of microorganisms, including pathogenic and non-pathogenic bacteria, is extremely important for a wide variety of applications including food safety, environmental studies, bio-terrorism threats, microbial forensics, criminal investigations and above all disease diagnosis. Although extremely powerful techniques such as those based on PCR and microarrays exist, they require sophisticated laboratory facilities along with elaborate sample preparation by trained researchers. Among different spectroscopic techniques, FTIR was used in the 1980s and 90s for bacterial identification. In the present study five species of Bacillus were isolated from the aerobic predigester chamber of Nisargruna Biogas Plant (NBP) and were identified to the species level by biochemical and molecular biological (16S ribosomal DNA sequence) methods. Those organisms were further checked by solid state spectroscopic absorbance measurements using a wide range of electromagnetic radiation (wavelength 200 nm to 25,000 nm) encompassing UV, visible, near Infrared and Infrared regions. UV-Vis and NIR spectroscopy was performed on dried bacterial cell suspension on silicon wafer in specular mode while FTIR was performed on KBr pellets containing the bacterial cells. Consistent and reproducible species specific spectra were obtained and sensitivity up to a level of 1000 cells was observed in FTIR with a DTGS detector. This clearly shows the potential of solid state spectroscopic techniques for simple, easy to implement, reliable and sensitive detection of bacteria from environmental samples.

Hybrid nanostructured C-dot decorated Fe3O4 electrode materials for superior electrochemical energy storage performance.

Research on energy storage devices has created a niche owing to the ever increasing demand for alternative energy production and its efficient utilisation. Here, a novel composite of Fe3O4 nanospheres and carbon quantum dots (C-dots) have been synthesized by a two step chemical route. Hybrids of C-dots with metal oxides can contribute to charge storage capacity through the combined effect of Faradaic pseudocapacitance from the Fe3O4 and the excellent electrical properties of the C-dots, which are a promising new member of the carbon family. The structural and morphological properties of the obtained Fe3O4-C hybrid nanocomposite were extensively studied. Detailed electrochemical studies show that the high performance of the magnetically responsive Fe3O4-C hybrid nanocomposite makes it an efficient supercapacitor electrode material. The remarkable improvement in the electrochemical performance of the Fe3O4-C hybrid nanocomposite is attributed to the Faradaic pseudocapacitance of Fe3O4 coupled with the high electrical conductivity of the C-dot which aided in fast transport and ionic motion during the charge-discharge cycles. Cyclic voltammetry and galvanostatic charge-discharge studies of Fe3O4-C hybrid nanocomposite show that the nanosystem delivers a maximum specific capacitance of ∼208 F g(-1). These results demonstrate that the novel Fe3O4-C hybrid nanocomposite has great potential as a high performance electrode material for supercapacitors.

Should an increase in cerebral neurochemicals following head kicks in full contact karate influence return to play?

BACKGROUND: Cerebral neurochemicals are markers of traumatic brain injury (TBI). OBJECTIVES: The aim of the study was to determine whether kicks to the head (KTH) in full contact karate significantly increased serum concentrations of protein S-100B, and neurone specific enolase (NSE). Kicks to the body (KTB) were also quantified to asses muscle tissue injury. Muscle damage was assessed by analysis of serum total creatine kinase (CK). METHODS: Twenty-four full contact karate practitioners were observed and filmed during actual competition and divided into two main groups post event: (1) Kicks to the head and body group (KTH): n = 12; mean ± SD; age, 30.4 ± 6.7 years; height, 1.74 ± 0.1 m; weight, 79.1 ± 2.1 kg; and (2): Kicks to the body group (KTB): n = 12; mean ± SD; age, 28.2 ± 6.5 years; height, 1.75 ± 0.1 m; weight, 79.2 ± 1.7 kg. The KTH group received direct kicks to the head, while group KTB received kicks and punches to the body. Blood samples were taken before and immediately post-combat for analysis of serum S-100B, NSE, CK and cardiac troponin. RESULTS: Significant increases in serum concentrations of S-100B (0.12 ± 0.17 vs. 0.37 ± 0.26, µg.L(-1)) and NSE (11.8 ± 4.1 vs. 20.2 ± 9.1 ng.mL(-1)) were encountered after combat in the KTH group and CK (123 ± 53 vs. 184 ± 103 U.L(-1)) in the KTB group (all P <0.05). CONCLUSIONS: Head kicks in full contact karate cause elevation of neurochemical markers associated with damaged brain tissue. The severity of injury is related to the early post-traumatic release of protein S-100B and NSE. The early kinetics and appearance post injury can reflect intracranial pathology, and suggest S-100B and NSE are extremely sensitive prognostic markers of TBI.

The burden of non-motor symptoms in Parkinson's disease using a self-completed non-motor questionnaire: a simple grading system.

BACKGROUND: Non-motor symptoms (NMS) of Parkinson's disease (PD) affect virtually every patient, yet they are under-recognized and under-treated. The NMS Questionnaire (NMSQuest) is a validated 30-item self-assessment instrument useful for NMS screening in clinic. OBJECTIVE: Development of a straight forward grading classification of the burden of non-motor symptoms in PD based on the number of NMS as assessed by the NMS Questionnaire. METHODS: In an observational, cross-sectional, international study of 383 consecutive patients distribution of the declared NMS as per NMSQuest was analyzed according to previously published levels based on the Non-Motor Symptoms Scale and also the median and interquartile range (IR, percentiles 25 and 75) of the total NMSQuest scores. After post hoc checking, these values were proposed as cut-off points for estimating NMS burden based only on the accumulation of symptoms. RESULTS: Burden and number of NMS correlate closely (r ≥ 0.80). On the basis of this finding, five levels (0 = No NMS to 4 = Very severe) of NMSQuest grading were proposed after identification of their cut-offs by ordinal logistic regression and median and interquartile range distribution. These values coincided almost completely with those obtained by median and interquartile range in an independent sample. Concordance between this classification and HY staging was weak (weighted kappa = 0.30), but was substantial (weighted kappa = 0.68) with the Non-Motor Symptoms Scale grading. CONCLUSION: Completion of NMSQuest and subsequent grading of the burden could allow the health care professional to approach the severity of NMS burden using the self completed NMSQuest in a primary care setting.