ACR White Paper on Magnetoencephalography and Magnetic Source Imaging: A Report from the ACR Commission on Neuroradiology.

Magnetoencephalography, the extracranial detection of tiny magnetic fields emanating from intracranial electrical activity of neurons, and its source modeling relation, magnetic source imaging, represent a powerful functional neuroimaging technique, able to detect and localize both spontaneous and evoked activity of the brain in health and disease. Recent years have seen an increased utilization of this technique for both clinical practice and research, in the United States and worldwide. This report summarizes current thinking, presents recommendations for clinical implementation, and offers an outlook for emerging new clinical indications.

Dysregulation of hepatic metabolism with obesity: factors influencing glucose and lipid metabolism.

The liver is a key metabolic organ that undertakes a multitude of physiological processes over the course of a day, including intrahepatic lipid and glucose metabolism which plays a key role in the regulation of systemic lipid and glucose concentrations. It serves as an intermediary organ between exogenous (dietary) and endogenous energy supply to extrahepatic organs. Thus, perturbations in hepatic metabolism can impact widely on metabolic disease risk. For example, the accumulation of intra-hepatocellular TAG (IHTG), for which adiposity is almost invariably a causative factor may result in dysregulation of metabolic pathways. Accumulation of IHTG is likely due to an imbalance between fatty acid delivery, synthesis and removal (via oxidation or export as TAG) from the liver; insulin plays a key role in all of these processes.

Fluorescence quenching based detection of nitroaromatics using luminescent triphenylamine carboxylic acids.

Detection of nitroaromatics employing greener techniques has been one of the most active research fields in chemistry. A series of triphenylamine (TPA) functionalized carboxylic acids were synthesized and characterized using various spectroscopic techniques including single-crystal X-ray diffraction analysis. The interaction of carboxylic acid-decorated TPAs with nitroaromatic compounds was photophysically explored using absorption and emission spectroscopy. Stern-Volmer plot accounts for the appreciable quenching constant of the TPA-acids. Density functional theory calculations were carried out to study the new compounds' frontier molecular orbital energy levels and the possible interactions with picrate anion and revealed an unusual charge transfer interaction between acids and picrate anion. The contact mode detection shows the TPA-acids can be used as dip-strip sensors for picric acid detection.

Neural dynamics of semantic categorization in semantic variant of primary progressive aphasia.

Semantic representations are processed along a posterior-to-anterior gradient reflecting a shift from perceptual (e.g., it has eight legs) to conceptual (e.g., venomous spiders are rare) information. One critical region is the anterior temporal lobe (ATL): patients with semantic variant primary progressive aphasia (svPPA), a clinical syndrome associated with ATL neurodegeneration, manifest a deep loss of semantic knowledge. We test the hypothesis that svPPA patients perform semantic tasks by over-recruiting areas implicated in perceptual processing. We compared MEG recordings of svPPA patients and healthy controls during a categorization task. While behavioral performance did not differ, svPPA patients showed indications of greater activation over bilateral occipital cortices and superior temporal gyrus, and inconsistent engagement of frontal regions. These findings suggest a pervasive reorganization of brain networks in response to ATL neurodegeneration: the loss of this critical hub leads to a dysregulated (semantic) control system, and defective semantic representations are seemingly compensated via enhanced perceptual processing.

Facile NMR approach for profiling curcuminoids present in turmeric.

Curcumin, together with demethoxycurcumin and bisdemethoxycurcumin as a whole called curcuminoids, is an active phytochemical constituent present in the turmeric. When it comes to their analysis, most will rely on UV-Visible spectroscopy, HPLC and LC-MS methods. Looking to improve productivity, time and simplicity, we are proposing a 1H NMR based approach for curcuminoids analysis and its applications to different geographical regions. In the present work, sample preparation protocol is reported for the simultaneous determination of curcuminoids using 1H NMR. For the quantification of curcuminoids, 6-7 ppm vinylic proton region in the 1H NMR spectrum was used, where acetone was observed as the suitable solvent in terms of curcuminoids solubility and proper resolution of peak. The result shows that curcumin (46.8-59.50%) was major among all varieties, followed by DMC (22.15-27.70%) and BDMC (17.52-30.29%) except in Andhrapradesh variety, where BDMC (30.29%) was more than DMC (22.89%). These studies were further supported by HPLC analysis.

Experimental infection and pathology of two highly pathogenic avian influenza H5N1 viruses isolated from crow and chicken in house crows (Corvus splendens).

We investigated the experimental infection of two highly pathogenic avian influenza H5N1 viruses isolated from crow (A/crow/Assam/142119/2008) and chicken (A/chicken/Sikkim/151466/2009) in house crows (Corvus splendens). Both viruses caused infection in crows, where four out of six and three out of six crows succumbed to H5N1 infection within 11 days post challenge by crow and chicken viruses, respectively. The major clinical signs in crows were wing paralysis, circling and torticollis. The virus shedding detected from swabs was not persistent in both crow nor chicken viruses. Both viruses were isolated more frequently from oral swabs than from cloacal swabs. Both virus strains were isolated from brain, lungs, heart, liver, pancreas, spleen, large intestines of crows that succumbed to H5N1 infection. The surviving birds seroconverted in response to H5N1 virus infection. Microscopically, both viruses caused coagulative necrosis in pancreas and kidneys. Brain showed gliosis and neuronal degeneration. This experimental study highlights that crows could be infected with H5N1 viruses from different hosts with minor differences in pathogenicity. Therefore, it is imperative to carry out surveillance of highly pathogenic avian influenza H5N1 virus in synanthropic birds along with biosecurity measures to mitigate the H5N1 spread in poultry population. Keywords: chicken virus; crow virus; highly pathogenic avian influenza; house crows.

Association of renin-angiotensin-aldosterone system genetic polymorphisms with maternal hypotension during spinal anaesthesia for caesarean delivery: a retrospective cohort study.

BACKGROUND: Unless prevented, hypotension occurs in up to 80% of normotensive women undergoing spinal anaesthesia for caesarean delivery. Renin-angiotensin-aldosterone system genetic polymorphisms have been associated with hypertensive disease, but few studies investigated effects on blood pressure regulation under spinal anaesthesia. We postulated that these polymorphisms increased vasodilation and maternal hypotension during spinal anaesthesia. METHODS: A retrospective secondary analysis of data from four prospective trials with similar inclusion/exclusion criteria evaluating phenylephrine/ephedrine delivery systems during spinal anaesthesia for elective caesarean delivery. Angiotensin type-1 receptor (AT1R) (A1166C), angiotensin-converting enzyme (ACE) (I/D), and aldosterone synthase CYP11B2 (C344T) polymorphisms were identified from stored specimens. The associations between the polymorphisms and hypotension (systolic blood pressure <80% of baseline), and vasopressor use, were determined by univariable and multivariable regression. RESULTS: Of 556 patients, 378 (68.0%) had hypotension. The AC/CC genotypes of AT1R (A1166C) were associated with hypotension by univariable analysis (OR 2.70, 95% CI 1.38 to 5.28, P=0.004]) and multivariable analysis (OR 3.65, [95% CI 1.68 to 7.94, P=0.004]) after adjustment for age, race, intravenous fluid volume, and block height. No difference in vasopressor use or adverse maternal or fetal outcomes were noted. Baseline characteristics were similar, with the exception of higher baseline blood pressure, block height, and intravenous fluid volume in the hypotensive group. There was no significant association between ACE and CYP11B2 polymorphisms and hypotension. CONCLUSION: AC/CC genotypes of AT1R (A1166C) polymorphism were associated with maternal hypotension under spinal anaesthesia for caesarean delivery. An association with cardiovascular indices and high-risk parturients should be examined.

Accuracy of Trained Community-based Rehabilitation Volunteers in Identification and Appropriate Referral of Adults with Perceived Visual Disability in an Urban-slum Setting in Southern India.

PURPOSE: The integration of primary eyecare into existing primary healthcare systems requires simple yet effective tools that do not overburden the grass-root level worker. The objective of this study was to test the accuracy of a questionnaire-based tool administered by trained community-based rehabilitation volunteers (CBRVs) in identifying persons with visual disability, proportions accessing referral pathway and barriers to uptake of eyecare services. METHODS: CBRVs working in the urban-slum service area of a teaching hospital were trained in administering a questionnaire-based tool derived from the World Health Organization (WHO) "Training in the community for people with disabilities" to a responsible adult member of the household. Post-training, they screened and referred adults with perceived visual problems. This tool was tested against two reference standards: (i) history of visual disability elicited by ophthalmologist; (ii) pre-set visual acuity and diagnosis criteria. RESULTS: Ten CBRVs screened 950 individuals of whom 805 (84.7%) were examined by an optometrist and ophthalmologist. Sensitivity and specificity of this method were 75% (95% CI 72-78%), 95.8% (95% CI 94-98%) respectively, using history and 60.2% (95% CI 57-63%), 91.8% (95% CI 90-94%) using clinical criteria as reference standard. Referral pathway was used by 91/221 (41.2%) referred individuals. The commonest barriers to accessing eye care were 'did not feel the need' (32.2%) and 'busy with work/household responsibilities' (30.2%). CONCLUSIONS: This questionnaire-based tool administered by grass-root level health workers to a responsible adult member of the family may be a promising screening method for identification and appropriate referral of persons with visual disability in the community.

Label-free peptide nucleic acid biosensor for visual detection of multiple strains of influenza A virus suitable for field applications.

Accurate and rapid diagnosis of Influenza A viruses (IAVs) is challenging because of multiple strains circulating in humans and animal populations, and the emergence of new strains. In this study, we demonstrate a simple and rapid strategy for visual detection of multiple strains of IAVs (H1 to H16 subtypes) using peptide nucleic acid (PNA) as a biosensor and unmodified gold nanoparticles (AuNPs) as a reporter. The design principle of the assay is based on the color change on account of free PNA-induced aggregation of AuNPs in the presence of non-complementary viral RNA sequence and vice-versa. The assay could detect IAV RNA with a visual limit of detection of 2.3 ng. The quantification of RNA with a considerable accuracy on a simple spectrophotometer was achieved on plotting the PNA-induced colorimetric changes (absorption ratio of A640/A520) in the presence of a varying concentration of complementary RNA. As a proof-of-concept, the visual assay was validated on 419 avian clinical samples and receiver operating characteristic (ROC) curve analysis showed a high diagnostic specificity (96.46%, 95% CI = 93.8 to 98.2) and sensitivity (82.41%, 95% CI = 73.9 to 89.1) when RT-qPCR was used as reference test. Hence, the simplicity, rapidity, and universality of this strategy make it a potential candidate visual assay for clinical diagnosis and surveillance of IAVs, especially in the resource-limited settings. The proposed strategy establishes new avenues for developing a simple and rapid diagnostic system for viral infections and biomolecules.

Craniofacial and oral manifestation of child abuse: A dental surgeon's guide.

Children should be given the privilege to mature in a loving, supportive family environment that promotes the development of an individual to his/her full potential. The abuse and neglect of children is a problem that pervades all segments of society. Dentists/forensic odontologists are in a strategic position to recognize mistreated children. While the detection of dental care neglect is an obvious responsibility for dentists, other types of child abuse and neglect also may present themselves in the dental office. Once this information is known to the dentist, he/she can join physicians in protecting children from injury.

Infectious dose-dependent accumulation of live highly pathogenic avian influenza H5N1 virus in chicken skeletal muscle-implications for public health.

Highly pathogenic avian influenza viruses (HPAIV) of H5N1 subtype are a major global threat to poultry and public health. Export of poultry products, such as chicken and duck meat, is a known source for the cross-boundary spread of HPAI H5N1 viruses. Humans get infected with HPAI H5N1 viruses either by close contact with infected poultry or through consumption of fresh/undercooked poultry meat. Skeletal muscle is the largest soft tissue in chicken that has been shown to contain virus during systemic HPAIV infection and supports productive virus infection. However, the time between infection of a chicken with H5N1 virus and presence of virus in muscle tissue is not yet known. Further, it is also not clear whether chicken infected with low doses of H5N1 virus that cause non-fatal subclinical infections continue to accumulate virus in skeletal muscle. We investigated the amount and duration of virus detection in skeletal muscle of chicken experimentally infected with different doses (102 , 103 and 104 EID50 ) of a HPAI H5N1 virus. Influenza viral antigen could be detected as early as 6 hr after infection and live virus was recovered from 48 hr after infection. Notably, chicken infected with lower levels of HPAI H5N1 virus (i.e., 102 EID50 ) did not die acutely, but continued to accumulate high levels of H5N1 virus in skeletal muscle until 6 days post-infection. Our data suggest that there is a potential risk of human exposure to H5N1 virus through meat from clinically healthy chicken infected with a low dose of virus. Our results highlight the need to implement rigorous monitoring systems to screen poultry meat from H5N1 endemic countries to limit the global spread of H5N1 viruses.

Norfloxacin salts of carboxylic acids curtail planktonic and biofilm mode of growth in ESKAPE pathogens.

AIMS: To enhance the antimicrobial and antibiofilm activity of norfloxacin against the planktonic and biofilm mode of growth in ESKAPE pathogens using chemically modified norfloxacin salts. METHODS AND RESULTS: Antimicrobial testing, synergy testing and time-kill curve analysis were performed to evaluate antibacterial effect of norfloxacin carboxylic acid salts against ESKAPE pathogens. In vivo efficacy to reduce bacterial bioburden was evaluated in zebrafish infection model. Crystal violet assay and live-dead staining were performed to discern antibiofilm effect. Membrane permeability, integrity and molecular docking studies were carried out to ascertain the mechanism of action. The carboxylic acid salts, relative to parent molecule norfloxacin, displayed two- to fourfold reduction in minimum inhibitory concentration against Staphylococcus aureus and Pseudomonas aeruginosa, in addition to displaying potent bacteriostatic effect against certain members of ESKAPE pathogens. In vivo treatments revealed that norfloxacin tartrate (SRIN2) reduced MRSA bioburden by greater than 1 log fold relative to parent molecule in the muscle tissue. In silico docking with gyrA of S. aureus showed increased affinity of SRIN2 towards DNA gyrase. The enhanced antibacterial effect of norfloxacin salts could be partially accounted by altered membrane permeability in S. aureus and perturbed membrane integrity in P. aeruginosa. Antibiofilm studies revealed that SRIN2 (norfloxacin tartrate) and SRIN3 (norfloxacin benzoate) exerted potent antibiofilm effect particularly against Gram-negative ESKAPE pathogens. The impaired colonization of both S. aureus and P. aeruginosa due to improved norfloxacin salts was further supported by live-dead imaging. CONCLUSION: Norfloxacin carboxylic acid salts can act as potential alternatives in terms of drug resensitization and reuse. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study shows that carboxylic acid salts of norfloxacin could be effectively employed to treat both planktonic- and biofilm-based infections caused by select members of ESKAPE pathogens.

Survivability of low pathogenic (H9N2) avian influenza virus in water in the presence of Atyopsis moluccensis (Bamboo shrimp).

Low pathogenic avian influenza virus (LPAIV) exhibits an ecological climax with the aquatic ecosystem. The most widely prevalent subtype of LPAIV is H9N2. Wild aquatic birds being the natural reservoirs and ducks, the "Trojan horses" for Avian Influenza Virus (AIV), can contaminate the natural water bodies inhabited by them. The virus can persist in the contaminated water from days to years depending upon the environmental conditions. Various aquatic species other than ducks can promote the persistence and transmission of AIV; however, studies on the role of aquatic fauna in persistence and transmission of avian influenza virus are scarce. This experiment was designed to evaluate the survivability of H9N2 LPAIV in water with and without Atyopsis moluccensis (bamboo shrimp) for a period of 12 days. The infectivity and amount of virus in water were calculated and were found to be significantly higher in water with A. moluccensis than in water without A. moluccensis. The study also showed that A. moluccensis can accumulate the virus mechanically which can infect chicken eggs up to 11 days. The virus transmission potential of A. moluccensis requires further studies.

Aryl fluoride functionalized graphene oxides for excellent room temperature ammonia sensitivity/selectivity.

Herein, we report the covalent functionalization of graphene oxide (GO) through ''click'' reaction and its applications towards ammonia sensing. This inimitable method of covalent functionalization involves linking GO with azide moiety and click coupling of different derivatives of aryl propargyl ether, which enhances the sensitivity towards ammonia. The functionalized GO were characterized using NMR, XRD, SEM, FT-IR, Raman, UV-Vis, TGA and DSC. Compared to pristine GO, the GO functionalized with Ar samples (GO-Ar) exhibit excellent room temperature ammonia sensing properties with good response/recovery characteristics. It has been observed that 2,3-difluoro and 2,3,4-trifluoro substituted aryl propargyl ether functionalized GO (GO-Ar2 and GO-Ar3) shows superior ammonia sensing with response/recovery of 63%/∼90% and 60%/100%, respectively at 20 ppm. The GO-Ar3 exhibits high sensitivity towards ammonia at 20-100 ppm. Computational studies supports the high sensitivity of GO-Ar towards ammonia due to its high adsorption energy.

Quantitative imaging of anti-phase domains by polarity sensitive orientation mapping using electron backscatter diffraction.

Advanced structural characterisation techniques which are rapid to use, non-destructive and structurally definitive on the nanoscale are in demand, especially for a detailed understanding of extended-defects and their influence on the properties of materials. We have applied the electron backscatter diffraction (EBSD) technique in a scanning electron microscope to non-destructively characterise and quantify antiphase domains (APDs) in GaP thin films grown on different (001) Si substrates with different offcuts. We were able to image and quantify APDs by relating the asymmetrical intensity distributions observed in the EBSD patterns acquired experimentally and comparing the same with the dynamical electron diffraction simulations. Additionally mean angular error maps were also plotted using automated cross-correlation based approaches to image APDs. Samples grown on substrates with a 4° offcut from the [110] do not show any APDs, whereas samples grown on the exactly oriented substrates contain APDs. The procedures described in our work can be adopted for characterising a wide range of other material systems possessing non-centrosymmetric point groups.

A giant testicular mixed germ cell tumour.

We present a case that we believe to be the largest mixed germ cell testicular tumour reported in the United Kingdom. A 23-year-old male was admitted to our urology department with a large scrotal swelling. The patient was found to have a giant left testicular tumour and a solitary lung metastasis at presentation. He underwent an emergency radical orchidectomy and subsequently received four cycles of bleomycin, etoposide and cisplatin chemotherapy. Four months after starting treatment, the tumour markers had normalised and a repeat staging computed tomography showed no active disease. The tumour reached that size because of the patient's failure to seek medical attention due to fear and embarrassment.

Non-functioning parathyroid adenoma: a rare differential diagnosis for vocal-cord paralysis.

Introduction Adenomas of the parathyroid gland typically present with symptoms of hyperparathyroidism, manifested by fatigue, bone pain, abdominal pain, weakness, dyspepsia, nephrolithiasis and skeletal bone disease. Here, we describe, for the first time, a case of a non-functioning benign tumour of the parathyroid gland presenting as vocal-cord paralysis. Case History A 49-year-old male presented with a 10-week history of dysphonia and the feeling of having 'something stuck in my throat'. History-taking elicited no other associated symptoms. Flexible nasal endoscopy demonstrated paralysis of the left vocal cord. Computed tomography of the neck revealed a cystic lesion, 18mm in diameter adjacent to the oesophagus. After more rigorous tests, a neck exploration, left hemithyroidectomy, excision of the left paratracheal mass and level-VI neck dissection was undertaken, without incident to the patient or surgical team. Histology was consistent with a parathyroid adenoma. Conclusions This case emphasises the importance of including adenomatous disease of the parathyroid gland in the differential diagnosis despite normal parathyroid status as a cause of vocal cord palsy.

Expression and purification of recombinant H5HA1 protein of H5N1 avian influenza virus in E. coli and its application in indirect ELISA.

The PCR amplified HA1 fragment of H5N1 (H5HA1) avian influenza virus (AIV) hemagglutinin gene was cloned into pET28a (+) expression vector and expressed in Rosetta Blue (DE3) pLysS cells. The recombinant H5HA1 (rH5HA1) protein purified by passive gel elution after SDS-PAGE of the inclusion bodies reacted specifically with H5N1 serum in Western blot analysis. A subtype specific indirect enzyme linked immunosorbent assay (iELISA) using the rH5HA1 protein as the coating antigen was developed for detecting antibodies to H5 subtype of AIV. The assay had 89.04% sensitivity and 95.95% specificity when compared with haemagglutination inhibition test. The Kappa value of 0.842 indicated a perfect agreement between the tests. The iELISA developed can be used for serosurveillance of avian influenza in chickens.

Relationship between M100 Auditory Evoked Response and Auditory Radiation Microstructure in 16p11.2 Deletion and Duplication Carriers.

BACKGROUND AND PURPOSE: Deletion and duplication of chromosome 16p11.2 (BP4-BP5) have been associated with developmental disorders such as autism spectrum disorders, and deletion subjects exhibit a large (20-ms) delay of the auditory evoked cortical response as measured by magnetoencephalography (M100 latency). The purpose of this study was to use a multimodal approach to test whether changes in white matter microstructure are associated with delayed M100 latency. MATERIALS AND METHODS: Thirty pediatric deletion carriers, 9 duplication carriers, and 39 control children were studied with both magnetoencephalography and diffusion MR imaging. The M100 latency and auditory system DTI measures were compared between groups and tested for correlation. RESULTS: In controls, white matter diffusivity significantly correlated with the speed of the M100 response. However, the relationship between structure and function appeared uncoupled in 16p11.2 copy number variation carriers. The alterations to auditory system white matter microstructure in the 16p11.2 deletion only partially accounted for the 20-ms M100 delay. Although both duplication and deletion groups exhibit abnormal white matter microstructure, only the deletion group has delayed M100 latency. CONCLUSIONS: These results indicate that gene dosage impacts factors other than white matter microstructure, which modulate conduction velocity.